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Chandra G, Lavikainen P, Siirtola P, Tamminen S, Ihalapathirana A, Laatikainen T, Martikainen J, Röning J. Explainable Prediction of Long-Term Glycated Hemoglobin Response Change in Finnish Patients with Type 2 Diabetes Following Drug Initiation Using Evidence-Based Machine Learning Approaches. Clin Epidemiol 2025; 17:225-240. [PMID: 40078337 PMCID: PMC11899941 DOI: 10.2147/clep.s505966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 02/18/2025] [Indexed: 03/14/2025] Open
Abstract
Purpose This study applied machine learning (ML) and explainable artificial intelligence (XAI) to predict changes in HbA1c levels, a critical biomarker for monitoring glycemic control, within 12 months of initiating a new antidiabetic drug in patients diagnosed with type 2 diabetes. It also aimed to identify the predictors associated with these changes. Patients and Methods Electronic health records (EHR) from 10,139 type 2 diabetes patients in North Karelia, Finland, were used to train models integrating randomized controlled trial (RCT)-derived HbA1c change values as predictors, creating offset models that integrate RCT insights with real-world data. Various ML models-including linear regression (LR), multi-layer perceptron (MLP), ridge regression (RR), random forest (RF), and XGBoost (XGB)-were evaluated using R² and RMSE metrics. Baseline models used data at or before drug initiation, while follow-up models included the first post-drug HbA1c measurement, improving performance by incorporating dynamic patient data. Model performance was also compared to expected HbA1c changes from clinical trials. Results Results showed that ML models outperform RCT model, while LR, MLP, and RR models had comparable performance, RF and XGB models exhibited overfitting. The follow-up MLP model outperformed the baseline MLP model, with higher R² scores (0.74, 0.65) and lower RMSE values (6.94, 7.62), compared to the baseline model (R²: 0.52, 0.54; RMSE: 9.27, 9.50). Key predictors of HbA1c change included baseline and post-drug initiation HbA1c values, fasting plasma glucose, and HDL cholesterol. Conclusion Using EHR and ML models allows for the development of more realistic and individualized predictions of HbA1c changes, accounting for more diverse patient populations and their heterogeneous nature, offering more tailored and effective treatment strategies for managing T2D. The use of XAI provided insights into the influence of specific predictors, enhancing model interpretability and clinical relevance. Future research will explore treatment selection models.
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Affiliation(s)
- Gunjan Chandra
- Biomimetics and Intelligent Systems Group, Faculty of Information Technology and Electrical Engineering, University of Oulu, Oulu, Finland
| | - Piia Lavikainen
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Pekka Siirtola
- Biomimetics and Intelligent Systems Group, Faculty of Information Technology and Electrical Engineering, University of Oulu, Oulu, Finland
| | - Satu Tamminen
- Biomimetics and Intelligent Systems Group, Faculty of Information Technology and Electrical Engineering, University of Oulu, Oulu, Finland
| | - Anusha Ihalapathirana
- Biomimetics and Intelligent Systems Group, Faculty of Information Technology and Electrical Engineering, University of Oulu, Oulu, Finland
| | - Tiina Laatikainen
- North Karelia Wellbeing Services County (Siun Sote), Joensuu, Finland
- Department of Public Health and Social Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | | | - Juha Röning
- Biomimetics and Intelligent Systems Group, Faculty of Information Technology and Electrical Engineering, University of Oulu, Oulu, Finland
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Dennis JM, Young KG, Cardoso P, Güdemann LM, McGovern AP, Farmer A, Holman RR, Sattar N, McKinley TJ, Pearson ER, Jones AG, Shields BM, Hattersley AT. A five-drug class model using routinely available clinical features to optimise prescribing in type 2 diabetes: a prediction model development and validation study. Lancet 2025; 405:701-714. [PMID: 40020703 DOI: 10.1016/s0140-6736(24)02617-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 11/25/2024] [Accepted: 11/27/2024] [Indexed: 03/03/2025]
Abstract
BACKGROUND Data to support individualised choice of optimal glucose-lowering therapy are scarce for people with type 2 diabetes. We aimed to establish whether routinely available clinical features can be used to predict the relative glycaemic effectiveness of five glucose-lowering drug classes. METHODS We developed and validated a five-drug class model to predict the relative glycaemic effectiveness, in terms of absolute 12-month glycated haemoglobin (HbA1c), for initiating dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter-2 inhibitors, sulfonylureas, and thiazolidinediones. The model used nine routinely available clinical features of people with type 2 diabetes at drug initiation as predictive factors (age, duration of diabetes, sex, and baseline HbA1c, BMI, estimated glomerular filtration rate, HDL cholesterol, total cholesterol, and alanine aminotransferase). The model was developed and validated with observational data from England (Clinical Practice Research Datalink [CPRD] Aurum), in people with type 2 diabetes aged 18-79 years initiating one of the five drug classes between Jan 1, 2004, and Oct 14, 2020, with holdback validation according to geographical region and calendar period. The model was further validated in individual-level data from three published randomised drug trials in type 2 diabetes (TriMaster three-drug crossover trial and two parallel-arm trials [NCT00622284 and NCT01167881]). For validation in CPRD, we assessed differences in observed glycaemic effectiveness between matched (1:1) concordant and discordant groups receiving therapy that was either concordant or discordant with model-predicted optimal therapy, with optimal therapy defined as the drug class with the highest predicted glycaemic effectiveness (ie, lowest predicted 12-month HbA1c). Further validation involved pairwise drug class comparisons in all datasets. We also evaluated associations with long-term outcomes in model-concordant and model-discordant groups in CPRD, assessing 5-year risks of glycaemic failure (confirmed HbA1c ≥69 mmol/mol), all-cause mortality, major adverse cardiovascular events or heart failure (MACE-HF) outcomes, renal progression, and microvascular complications using Cox proportional hazards regression adjusting for relevant demographic and clinical covariates. FINDINGS The five-drug class model was developed from 100 107 drug initiations in CPRD. In the overall CPRD cohort (combined development and validation cohorts), 32 305 (15·2%) of 212 166 drug initiations were of the model-predicted optimal therapy. In model-concordant groups, mean observed 12-month HbA1c benefit was 5·3 mmol/mol (95% CI 4·9-5·7) in the CPRD geographical validation cohort (n=24 746 drug initiations, n=12 373 matched pairs) and 5·0 mmol/mol (4·3-5·6) in the CPRD temporal validation cohort (n=9682 drug initiations, n=4841 matched pairs) compared with matched model-discordant groups. Predicted HbA1c differences were well calibrated with observed HbA1c differences in the three clinical trials in pairwise drug class comparisons, and in pairwise comparisons of the five drug classes in CPRD. 5-year risk of glycaemic failure was lower in model-concordant versus model-discordant groups in CPRD (adjusted hazard ratio [aHR] 0·62 [95% CI 0·59-0·64]). For long-term non-glycaemic outcomes, model-concordant versus model-discordant groups had a similar 5-year risk of all-cause mortality (aHR 0·95 [0·83-1·09]) and lower risks of MACE-HF outcomes (aHR 0·85 [0·76-0·95]), renal progression (aHR 0·71 [0·64-0·79]), and microvascular complications (aHR 0·86 [0·78-0·96]). INTERPRETATION We have developed a five-drug class model that uses routine clinical data to identify optimal glucose-lowering therapies for people with type 2 diabetes. Individuals on model-predicted optimal therapy had lower 12-month HbA1c, were less likely to need additional glucose-lowering therapy, and had a lower risk of diabetes complications than individuals on non-optimal therapy. With setting-specific optimisation, the use of routinely collected parameters means that the model is easy to introduce to clinical care in most countries worldwide. FUNDING UK Medical Research Council.
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Affiliation(s)
- John M Dennis
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK.
| | - Katherine G Young
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK
| | - Pedro Cardoso
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK
| | - Laura M Güdemann
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK
| | - Andrew P McGovern
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK
| | - Andrew Farmer
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Rury R Holman
- Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Trevelyan J McKinley
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK
| | - Ewan R Pearson
- Division of Diabetes, Endocrinology and Reproductive Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Angus G Jones
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK
| | - Beverley M Shields
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK
| | - Andrew T Hattersley
- Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK
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Tunis SR, Shafrin J, Than KS, Whittington MD, Willke RJ, Bharmal M. Use of real-world evidence in the Medicare Drug Price Negotiation Program: A checklist for the Centers for Medicare and Medicaid Services and manufacturers. HEALTH AFFAIRS SCHOLAR 2025; 3:qxaf030. [PMID: 40123993 PMCID: PMC11926674 DOI: 10.1093/haschl/qxaf030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/31/2025] [Accepted: 03/18/2025] [Indexed: 03/25/2025]
Abstract
Under the Inflation Reduction Act's (IRA's) - Medicare Drug Price Negotiation Program, the Centers for Medicare & Medicaid Services' (CMS's) "maximum fair price" must be informed by evidence on factors such as therapeutic advance of the selected drug compared with its alternative, comparative effectiveness across clinical and patient-reported outcomes, the impact on specific populations, and the ability to address unmet medical needs. This paper describes how real-world evidence could improve CMS decision-making and creates a best practices checklist to help CMS evaluate the quality of any manufacturer-submitted evidence. The checklist was developed in four steps: (i) identification of the IRA requirements for determining the maximum fair price through a review of official guidance from CMS, (ii) assessment of provisions that could be supported by real-world evidence (RWE) in addition to clinical trial evidence, (iii) literature review on existing best-practice guidelines relevant to RWE, and (iv) consolidation of these RWE guidelines into a checklist through a series of web conference discussions among experts. The checklist aims to improve the quality of the information available to CMS during the drug price negotiation process.
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Affiliation(s)
- Sean R Tunis
- Center for Evaluation of Value and Risk in Health, Tufts Medical Center, Boston, MA 02111, United States
- Rubix Health LLC, Baltimore, MD 21210, United States
| | - Jason Shafrin
- Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, United States
- Center for Healthcare Economics and Policy, FTI Consulting, Los Angeles, CA 90071, United States
| | - Kyi-Sin Than
- Center for Healthcare Economics and Policy, FTI Consulting, Washington, DC 20004, United States
| | - Melanie D Whittington
- Center for the Evaluation of Value and Risk in Health (CEVR), Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, Boston, MA 02111, United States
- Leerink Center for Pharmacoeconomics, MEDACorp LLC, Boston, MA 02109, United States
| | - Richard J Willke
- Scintegral Health Economics, Soddy Daisy, TN 37379, United States
| | - Murtuza Bharmal
- Oncology Outcomes Research, AstraZeneca, Boston, MA 02210, United States
- School of Pharmacy, Department of Pharmaceutical Systems and Policy, West Virginia University, Morgantown, WV 26501, United States
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Atkinson-Clement C, Junor A, Kaiser M. Neuromodulation perception by the general public. Sci Rep 2025; 15:5584. [PMID: 39955336 PMCID: PMC11830022 DOI: 10.1038/s41598-025-89437-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 02/05/2025] [Indexed: 02/17/2025] Open
Abstract
The development of neurotechnologies offers exciting opportunities for novel brain interventions. Public perception plays a crucial role in determining the success and acceptance of these interventions. This study aimed to understand the general non-expert population's representation of neuromodulation and their preferences for common methods such as pharmaceutical drugs, brain implants, ultrasound, magnetic, and electrical stimulations. We conducted a comprehensive online survey with 784 participants to assess their perception of neuromodulation before and after providing information. We also asked the participants to rank their preferences for different neuromodulation techniques after being provided with information. Statistical analyses included inferential non-linear models and free-text data mining. Our findings revealed that overall, neuromodulation was positively perceived by the participants. Furthermore, providing information resulted in a significant improvement in participants' perception of neuromodulation. Ultrasound stimulation emerged as the most preferred treatment choice, while pharmaceutical drugs were considered a middle-choice option and brain implants ranked last due to safety concerns. Healthcare providers could benefit from enhancing patient education and awareness to promote informed decision-making and improve treatment adherence. Additionally, stakeholders have to address the existing distrust surrounding pharmaceutical drugs and prioritize the development and promotion of safe, non-invasive neuromodulation treatments.
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Affiliation(s)
- Cyril Atkinson-Clement
- Precision Imaging, School of Medicine, University of Nottingham, Nottingham, UK.
- NIHR Biomedical Research Centre, University of Nottingham, Nottingham, UK.
| | - Andrea Junor
- Precision Imaging, School of Medicine, University of Nottingham, Nottingham, UK
- NIHR Biomedical Research Centre, University of Nottingham, Nottingham, UK
| | - Marcus Kaiser
- Precision Imaging, School of Medicine, University of Nottingham, Nottingham, UK
- NIHR Biomedical Research Centre, University of Nottingham, Nottingham, UK
- Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Lee CH, Lui DTW, Mak LY, Fong CHY, Chan KSW, Mak JHC, Cheung CYY, Chow WS, Woo YC, Yuen MF, Seto WK, Lam KSL. Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes-A real-world study. Diabetes Obes Metab 2025; 27:574-582. [PMID: 39497579 DOI: 10.1111/dom.16049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/20/2024] [Accepted: 10/22/2024] [Indexed: 01/07/2025]
Abstract
AIMS Both pioglitazone and glucagon-like peptide 1 receptor agonists (GLP1RA) alone improve metabolic dysfunction-associated steatohepatitis (MASH) in randomized clinical trials, whereas preclinical studies suggested MASH benefits with sodium glucose co-transporter 2 inhibitors (SGLT2i). In the real world, patients with type 2 diabetes often require multiple agents for glycaemic control. Here, we investigated the benefits of combining these agents on risks of MASH. MATERIALS AND METHODS Longitudinal changes in FibroScan-aspartate aminotransferase (FAST) score were measured in 888 patients with type 2 diabetes. Use of pioglitazone, GLP1RA and/or SGLT2i was defined as continuous prescriptions of ≥180 days prior to their last reassessment FibroScan. Multivariable logistic regression analysis was conducted to evaluate the associations between use of these agents and FAST score changes. RESULTS Over a median follow-up of 3.9 years, the increasing number of these agents used was significantly associated with more reductions in FAST score (p for trend <0.01). Dual combination was independently associated with a higher likelihood of achieving low FAST score at reassessment than single use of any of these agents (odds ratio [OR] 2.84, p = 0.01). Among the different drug combinations, using SGLT2i and pioglitazone (median dose 15 mg daily) together, as compared to not using any of these three agents, was associated with a higher likelihood of both low FAST score at reassessment (OR 6.51, p = 0.008) and FAST score regression (OR 12.52, p = 0.009), after adjusting for changes in glycaemic control and body weight during the study. CONCLUSIONS Combining SGLT2i and pioglitazone is a potentially useful strategy to ameliorate 'at-risk' MASH in patients with type 2 diabetes.
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Affiliation(s)
- Chi-Ho Lee
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - David Tak-Wai Lui
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Lung-Yi Mak
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory of Liver Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Carol Ho-Yi Fong
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Kylie Sze-Wing Chan
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Jimmy Ho-Cheung Mak
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Chloe Yu-Yan Cheung
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Wing-Sun Chow
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Yu-Cho Woo
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Man-Fung Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory of Liver Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Wai-Kay Seto
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory of Liver Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Karen Siu-Ling Lam
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
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Zou L, Li J, Xiang H, Tan J, Zeng Y. Knowledge, attitude and practice towards multiple myeloma among medical staff in Enshi Region. Sci Rep 2025; 15:3406. [PMID: 39870732 PMCID: PMC11772647 DOI: 10.1038/s41598-025-88079-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 01/23/2025] [Indexed: 01/29/2025] Open
Abstract
A study in the Enshi Region between Sept-Nov 2023 assessed medical staff's knowledge, attitude, and practice regarding multiple myeloma. The disease significantly impacts physical health, quality of life, and mental well-being. Medical professionals play crucial roles in its prevention and treatment. Analysis used Pearson's correlation, logistic regression, and structural equation model (SEM). A total of 229 valid questionnaires were collected, with 68.6% of female participants, and 42.4% aged 31-40 years. The knowledge, attitude, and practice scores were 36.27 ± 4.97 (range: 25-53), 42.40 ± 5.78 (range: 30-56), and 29.71 ± 6.41 (range: 7-35), respectively. Pearson's correlation analysis revealed significantly positive correlation between knowledge and attitude. Moreover, in both univariate and multivariate analysis, knowledge showed positive association with attitude. Several demographic factors independently associated with KAP scores were identified, including education level, age, occupation type, and frequency of academic conferences or medical education activities per year. SEM further indicated direct association between attitude and practice (β = 0.320, 95%CI: 0.189-0.452, P < 0.001). In the Enshi Region, medical staff displayed moderate knowledge, neutral attitudes, and proactive practices towards multiple myeloma. Moreover, significant positive association was found between knowledge and attitude. These discoveries provided valuable perspectives to the development of healthcare interventions and educational initiatives for improving medical staff's knowledge, attitudes, and practices.
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Affiliation(s)
- Luping Zou
- Department of Hematology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China
| | - Jinhua Li
- Department of ophthalmology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China
| | - Hang Xiang
- Department of Hematology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China.
| | - Jun Tan
- Department of Hematology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China
| | - Yan Zeng
- Department of Hematology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China
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Erbakan AN, Arslan Bahadır M, Kaya FN, Güleç B, Vural Keskinler M, Aktemur Çelik Ü, Faydalıel Ö, Mesçi B, Oğuz A. Association of the glycemic background patterns and the diabetes management efficacy in poorly controlled type 2 diabetes. World J Diabetes 2025; 16:98322. [PMID: 39817217 PMCID: PMC11718454 DOI: 10.4239/wjd.v16.i1.98322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 08/26/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Inadequate glycemic control in patients with type 2 diabetes (T2DM) is a major public health problem and a significant risk factor for the progression of diabetic complications. AIM To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin (HbA1c) ≥ 10% and varying backgrounds of glycemic control. METHODS This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months. Participants were categorized into four groups based on prior glycemic history: Newly diagnosed, previously well controlled with recent worsening, previously off-target but now worsening, and HbA1c consistently above 10%. HbA1c levels were monitored quarterly, and patients received medical, educational, and dietary support as needed. The analysis focused on the success rates of good glycemic control and the associated factors within each group. RESULTS The study showed significant improvements in HbA1c levels in all participants. The most significant improvement was observed in individuals newly diagnosed with diabetes: 65% achieved an HbA1c target of ≤ 7%. The results varied between participants with different glycemic control histories, followed by decreasing success rates: 39% in participants with previously good glycemic control, 21% in participants whose glycemic control had deteriorated compared to before, and only 10% in participants with persistently poor control, with mean HbA1c levels of 6.3%, 7.7%, 8.2%, and 9.7%, respectively. After one year, 65.2% of the "newly diagnosed patients", 39.3% in the "previously controlled group", 21.9% in the "previously off-target but now worsened'" group and 10% in the "poorly controlled from the start" group had achieved HbA1c levels of 7 and below. CONCLUSION In poorly controlled diabetes, the rate at which treatment goals are achieved is associated with the glycemic background characteristics, emphasizing the need for tailored strategies. Therefore, different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.
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Affiliation(s)
- Ayşe N Erbakan
- Department of Internal Medicine, Prof Dr Suleyman Yalcin City Hospital, Istanbul Medeniyet University, Istanbul 34722, Türkiye
| | - Müzeyyen Arslan Bahadır
- Department of Internal Medicine, Prof Dr Suleyman Yalcin City Hospital, Istanbul Medeniyet University, Istanbul 34722, Türkiye
| | - Fatoş N Kaya
- Department of Internal Medicine, Prof Dr Suleyman Yalcin City Hospital, Istanbul Medeniyet University, Istanbul 34722, Türkiye
| | - Büşra Güleç
- Department of Internal Medicine, Prof Dr Suleyman Yalcin City Hospital, Istanbul Medeniyet University, Istanbul 34722, Türkiye
| | - Miraç Vural Keskinler
- Department of Internal Medicine, Prof Dr Suleyman Yalcin City Hospital, Istanbul Medeniyet University, Istanbul 34722, Türkiye
| | | | - Özge Faydalıel
- Department of Internal Medicine, Prof Dr Suleyman Yalcin City Hospital, Istanbul Medeniyet University, Istanbul 34722, Türkiye
| | - Banu Mesçi
- Department of Internal Medicine, Prof Dr Suleyman Yalcin City Hospital, Istanbul Medeniyet University, Istanbul 34722, Türkiye
| | - Aytekin Oğuz
- Department of Internal Medicine, Prof Dr Suleyman Yalcin City Hospital, Istanbul Medeniyet University, Istanbul 34722, Türkiye
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Khunti K, Zaccardi F, Amod A, Aroda VR, Aschner P, Colagiuri S, Mohan V, Chan JCN. Glycaemic control is still central in the hierarchy of priorities in type 2 diabetes management. Diabetologia 2025; 68:17-28. [PMID: 39155282 PMCID: PMC11663178 DOI: 10.1007/s00125-024-06254-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 07/15/2024] [Indexed: 08/20/2024]
Abstract
A panel of primary care and diabetes specialists conducted focused literature searches on the current role of glycaemic control in the management of type 2 diabetes and revisited the evolution of evidence supporting the importance of early and intensive blood glucose control as a central strategy to reduce the risk of adverse long-term outcomes. The optimal approach to type 2 diabetes management has evolved over time as the evidence base has expanded from data from trials that established the role of optimising glycaemic control to recent data from cardiovascular outcomes trials (CVOTs) demonstrating organ-protective effects of newer glucose-lowering drugs (GLDs). The results from these CVOTs were derived mainly from people with type 2 diabetes and prior cardiovascular and kidney disease or multiple risk factors. In more recent years, earlier diagnosis in high-risk individuals has contributed to the large proportion of people with type 2 diabetes who do not have complications. In these individuals, a legacy effect of early and optimal control of blood glucose and cardiometabolic risk factors has been proven to reduce cardiovascular and kidney disease events and all-cause mortality. As there is a lack of RCTs investigating the potential synergistic effects of intensive glucose control and organ-protective effects of newer GLDs, this article re-evaluates the evolution of the scientific evidence and highlights the importance of integrating glycaemic control as a pivotal early therapeutic goal in most people with type 2 diabetes, while targeting existing cardiovascular and kidney disease. We also emphasise the importance of implementing multifactorial management using a multidisciplinary approach to facilitate regular review, patient empowerment and the possibility of tailoring interventions to account for the heterogeneity of type 2 diabetes.
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Affiliation(s)
- Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK.
| | | | - Aslam Amod
- Department of Endocrinology, Nelson Mandela School of Medicine and Life Chatsmed Garden Hospital, Durban, South Africa
| | - Vanita R Aroda
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Pablo Aschner
- Endocrinology Unit, Javeriana University and San Ignacio University Hospital, Bogotá, Colombia
| | - Stephen Colagiuri
- Boden Collaboration, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
| | - Viswanathan Mohan
- Department of Diabetology, Dr Mohan's Diabetes Specialities Centre and Madras Diabetes Research Foundation, Chennai, India
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
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Chen AS, Hajduk AM, Grimshaw AA, Fried TR, Jastreboff AM, Lipska KJ. Efficacy of antiobesity medications for weight reduction in older adults: a systematic review. Obesity (Silver Spring) 2024. [PMID: 39725567 DOI: 10.1002/oby.24160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 08/29/2024] [Accepted: 09/01/2024] [Indexed: 12/28/2024]
Abstract
OBJECTIVE The objective of this study was to examine weight reduction and adverse events associated with use of antiobesity medications (AOMs) in older adults ages ≥65 years. METHODS Seven databases were searched for studies evaluating weight reduction of Food and Drug Administration (FDA)-approved AOMs. Studies had to include adults ages ≥65 years with obesity (BMI ≥ 30 kg/m2 or ≥27 kg/m2 with one weight-related condition), with independent analysis of weight reduction for adults ages ≥65 years. Two coauthors extracted and evaluated studies for risk of bias using standardized forms. RESULTS Six experimental studies (five secondary analyses of randomized clinical trial data and one single-arm trial) and two observational studies met inclusion criteria. Seven medications were studied. Sample size of older adults ranged from 13 to 6728. Experimental studies predominantly included patients with concurrent prediabetes or cardiovascular disease. All studies found statistically significant weight reduction between intervention and placebo groups or compared with baseline weight. Few studies reported on adverse events. CONCLUSIONS Limited evidence suggests weight reduction of AOMs in older adults, with the best current evidence for the use of semaglutide in older adults with obesity and cardiovascular disease. Larger, more inclusive studies of older adults are needed to guide clinical care and determine the tolerability of AOMs for older adults.
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Affiliation(s)
- Alissa S Chen
- National Clinician Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Alexandra M Hajduk
- Section of Geriatrics, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Alyssa A Grimshaw
- Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, Connecticut, USA
| | - Terri R Fried
- Section of Geriatrics, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Ania M Jastreboff
- Yale Obesity Research Center (Y-Weight), Yale School of Medicine, New Haven, Connecticut, USA
- Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Kasia J Lipska
- Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
- Center for Outcomes Research and Evaluation, Yale-New Haven Health System, New Haven, Connecticut, USA
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10
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Haller N, Lutz TA. Incretin therapy in feline diabetes mellitus - A review of the current state of research. Domest Anim Endocrinol 2024; 89:106869. [PMID: 38870560 DOI: 10.1016/j.domaniend.2024.106869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 05/21/2024] [Accepted: 06/06/2024] [Indexed: 06/15/2024]
Abstract
Incretin hormones potentiate the glucose-induced insulin secretion following enteral nutrient intake. The best characterised incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) which are produced in and secreted from the gut in response to nutrient ingestion. The property of incretins to enhance endogenous insulin secretion only at elevated blood glucose levels makes them interesting therapeutics for type 2 diabetes mellitus with a better safety profile than exogenous insulin. While incretin therapeutics (especially GLP-1 agonists, and more recently also GLP-1 / GIP dual agonists and other drugs that influence the incretin metabolism (e.g., dipeptidyl peptidase-4 (DPP-4) inhibitors)) are already widely used treatment options for human type 2 diabetes, these drugs are not yet approved for the therapy of feline diabetes mellitus. This review provides an introduction to incretins and feline diabetes mellitus in general and summarises the current study situation on incretins as therapeutics for feline diabetes mellitus to assess their possible future potential in feline medicine. Studies to date on the use of GLP-1 receptor agonists (GLP-1RA) in healthy cats largely confirm their insulinotropic effect known from other species. In diabetic cats, GLP-1RAs appear to significantly reduce glycaemic variability (GV, an indicator for the quality of glycaemic control), which is important for the management of the disease and prevention of long-term complications. However, for widespread use in feline diabetes mellitus, further studies are required that include larger numbers of diabetic cats, and that consider and test a possible need for dose adjustments to overweight and diabetic cats. Also evaluation of the outcome of GLP-1RA monotherapy will be neceessary.
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Affiliation(s)
- Nina Haller
- Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 204, CH 8057 Zurich, Switzerland
| | - Thomas A Lutz
- Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH 8057 Zurich, Switzerland.
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11
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Lv L, Brady BL, Xie L, Guevarra M, Turchin A. Adherence and persistence among people with type 2 diabetes newly initiating oral semaglutide versus DPP-4is in a US real-world setting. Prim Care Diabetes 2024; 18:511-517. [PMID: 38991896 DOI: 10.1016/j.pcd.2024.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 06/26/2024] [Accepted: 06/29/2024] [Indexed: 07/13/2024]
Abstract
AIMS To investigate real-world treatment adherence and persistence in people with type 2 diabetes newly initiating oral semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), or a dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS This retrospective cohort study used the Merative™ MarketScan® Commercial and Medicare databases. Index date was the first fill for the cohort medication. Adherence was defined as proportion of days covered (PDC) over the 12-month post-index period ('adherent' = ≥0.8). Persistence was number of days until discontinuation, based on a 45-day gap. Results were compared between cohorts using inverse probability treatment weighting. RESULTS Oral semaglutide (n=5485) and DPP-4i (n=4980) cohorts had similar percentages of people who were adherent (PDC ≥0.8; 41.6 % vs. 42.9 %; P = 0.182) and persistent for ≥9 months (45.0 % vs. 46.3 %; P = 0.185). The DPP-4i cohort used significantly more anti-diabetic medication (ADM) classes over the post-index period (mean±SD: 2.6±1.0 vs. 2.9±1.1, P < 0.001), with 23.2 % filling a GLP-1 RA in the post-period. CONCLUSIONS Adherence and persistence were similar between cohorts. However, there are potential benefits to prescribing oral semaglutide over DPP-4is, including reduced need for additional ADM.
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Affiliation(s)
- Lei Lv
- Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536, USA.
| | - Brenna L Brady
- Merative, 100 Phoenix Dr Suite 200, Ann Arbor, MI 48108, USA
| | - Lin Xie
- Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536, USA
| | - Mico Guevarra
- Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536, USA
| | - Alexander Turchin
- Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
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12
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Buckley A, Suliman S, Allum M, Mohammed N, Lessan N, le Roux CW, Suliman M. Real world use of tirzepatide in the treatment of type 2 diabetes in an Arab population. Diabetes Obes Metab 2024; 26:3381-3391. [PMID: 38783825 DOI: 10.1111/dom.15680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 05/01/2024] [Accepted: 05/09/2024] [Indexed: 05/25/2024]
Abstract
AIM Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) dual receptor agonist (RA) that reduces glycated haemoglobin (HbA1c) and weight in patients with type 2 diabetes. We assessed the effectiveness of tirzepatide in real-world use in an Arab population. METHODS Review of clinical data from a specialist outpatient diabetes centre; study time points and outcome measures were pre-specified. RESULTS Tirzepatide was initiated in 8945 patients between 24 October 2022 and 31 December 2023. Of these, 3686 individuals reached 40 weeks of follow-up. At initiation, the mean ± SD age was 54.1 ± 11.5 years, body mass index 34.6 ± 6.0 kg/m2 and HbA1c 7.3 ± 1.5% (56 ± 17 mmol/mol); 2296 (62%) were switched to tirzepatide from another GLP-RA and 317 (8.6%) reported previous bariatric surgery. The maximum dose dispensed was ≥12.5 mg/week in 1087, 7.5-10.0 mg/week in 1688 and 2.5-5.0 mg/week in 911. The mean 40-week reduction in HbA1c was 0.6 ± 1.2% (8 ± 13 mmol/mol) and the reduction in weight was 4.5 ± 6.9 kg (4.8 ± 7.3%). GLP-RA-naïve patients experienced a significantly greater reduction in HbA1c [1.0 ± 1.3% (11 ± 14 mmol/mol) versus 0.5 ± 1.2% (6 ± 13 mmol/mol), p < .0001] and weight (7.2 ± 8.6 vs. 4.2 ± 6.6 kg, p < .0001) compared with previously exposed individuals. Post-metabolic bariatric surgery patients lost significantly more weight (7.8 ± 9.4 vs. 4.5 ± 7.0 kg, p < .0001). Improvements in blood pressure, lipid profile, and liver transaminases were noted at 40 weeks. Tirzepatide was well tolerated, with 288 (7.8%) of patients discontinuing treatment because of adverse effects, predominantly gastrointestinal. CONCLUSION In real-world use, tirzepatide significantly reduced HbA1c levels and weight and was well tolerated. Previous GLP-RA use was associated with significantly lesser HbA1c and weight reduction, and previous metabolic bariatric surgery was associated with greater weight loss.
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Affiliation(s)
- Adam Buckley
- Imperial College London Diabetes Centre (ICLDC), Abu Dhabi, UAE
| | - Sara Suliman
- Imperial College London Diabetes Centre (ICLDC), Abu Dhabi, UAE
| | - Matthew Allum
- Imperial College London Diabetes Centre (ICLDC), Abu Dhabi, UAE
| | - Nagi Mohammed
- Imperial College London Diabetes Centre (ICLDC), Abu Dhabi, UAE
| | - Nader Lessan
- Imperial College London Diabetes Centre (ICLDC), Abu Dhabi, UAE
| | - Carel W le Roux
- Divisions of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland
| | - Mohamed Suliman
- Imperial College London Diabetes Centre (ICLDC), Abu Dhabi, UAE
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13
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Talay L, Vickers M. Patient Adherence to a Real-World Digital, Asynchronous Weight Loss Program in Australia That Combines Behavioural and GLP-1 RA Therapy: A Mixed Methods Study. Behav Sci (Basel) 2024; 14:480. [PMID: 38920813 PMCID: PMC11200677 DOI: 10.3390/bs14060480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/30/2024] [Accepted: 06/03/2024] [Indexed: 06/27/2024] Open
Abstract
Increasingly large numbers of people are using digital weight loss services (DWLSs) to treat being overweight and obesity. Although it is widely agreed that digital modalities improve access to care in general, obesity stakeholders remain concerned that many DWLSs are not comprehensive or sustainable enough to deliver meaningful health outcomes. This study adopted a mixed methods approach to assess why and after how long patients tend to discontinue Australia's largest DWLS, a program that combines behavioural and pharmacological therapy under the guidance of a multidisciplinary care team. We found that in a cohort of patients who commenced the Eucalyptus DWLS between January and June 2022 (n = 5604), the mean program adherence was 171.2 (±158.2) days. Inadequate supplying of a patient's desired glucose-like peptide-1 receptor agonist medication was the most common reason for discontinuation (43.7%), followed by program cost (26.2%), result dissatisfaction (9.9%), and service dissatisfaction (7.2%). Statistical tests revealed that ethnicity and age both had a significant effect on patient adherence. These findings suggest that DWLSs have the potential to improve access to comprehensive, continuous obesity care, but care models need to improve upon the one observed in the Eucalyptus Australia DWLS to mitigate common real-world program attrition factors.
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Affiliation(s)
- Louis Talay
- Faculty of Arts and Social Sciences, University of Sydney, Camperdown, NSW 2050, Australia
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14
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Gimeno EJ, Bøgelund M, Larsen S, Okkels A, Reitzel SB, Ren H, Orozco-Beltran D. Adherence and Persistence to Basal Insulin Among People with Type 2 Diabetes in Europe: A Systematic Literature Review and Meta-analysis. Diabetes Ther 2024; 15:1047-1067. [PMID: 38520604 PMCID: PMC11043249 DOI: 10.1007/s13300-024-01559-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 02/27/2024] [Indexed: 03/25/2024] Open
Abstract
INTRODUCTION Diabetes is associated with a number of complications, particularly if glycaemic targets are not achieved. Glycaemic control is highly linked to treatment persistence and adherence. To understand the burden of poor persistence and adherence, this systematic literature review identified existing evidence regarding basal insulin adherence/non-adherence and persistence/non-persistence among people with diabetes in Western Europe (defined as the UK, France, Spain, Switzerland, the Netherlands, Ireland, Austria, Portugal, Denmark, Norway, Sweden, Finland, Italy, Germany, Iceland and Belgium). METHODS Eligible studies were systematically identified from two databases, Medline and Embase (published between 2012 and June 2022). Conference abstracts from ISPOR and EASD were manually included. Identified studies were screened by two independent reviewers in a two-step blinded process. The eligibility of studies was decided on the basis of pre-established criteria. A proportional meta-analysis and comparative narrative analyses were conducted to analyse the included studies. RESULTS Twelve studies were identified. Proportions of adherence/non-adherence and persistence/non-persistence varied across studies. Pooled rates of non-persistence at 6, 12 and 18 months were 20.3% (95% CI 13.8; 27.8), 33.8% (95% CI 24.1; 44.3) and 36.5% (95% CI 33.6; 39.4), respectively. In the literature, the proportion of adherent people ranged from 41% to 64% (using the outcome measure medication possession ratio (MPR) > 80%), with a pooled rate of 55.6% (95% CI 45.3; 65.6), suggesting that approximately 44% of people with type 2 diabetes (T2D) are non-adherent. CONCLUSION The results highlight that almost half of patients with T2D in Western Europe have poor adherence to insulin therapy and, at 18 months, one in three patients do not persist on treatment. These findings call for new basal insulin therapies and diabetes management strategies that can improve treatment persistence and adherence among people with T2D.
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Affiliation(s)
- Esteban J Gimeno
- Faculty of Medicine, Universidad Europea de Madrid, Madrid, Spain
| | - Mette Bøgelund
- EY Economics, Dirch Passers Allé 36, 2000, Frederiksberg, Denmark
| | - Sara Larsen
- Novo Nordisk, Region North West Europe, Kay Fiskers Plads 10, 7th floor, 2300, Copenhagen S, Denmark
| | - Anna Okkels
- EY Economics, Dirch Passers Allé 36, 2000, Frederiksberg, Denmark
| | - Signe B Reitzel
- EY Economics, Dirch Passers Allé 36, 2000, Frederiksberg, Denmark
| | - Hongye Ren
- Novo Nordisk, Region North West Europe, Kay Fiskers Plads 10, 7th floor, 2300, Copenhagen S, Denmark.
| | - Domingo Orozco-Beltran
- Cátedra de Medicina de Familia, Departamento de Medicina Clínica, Universidad Miguel Hernández, Alicante, Spain
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15
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Cardoso P, Young KG, Nair ATN, Hopkins R, McGovern AP, Haider E, Karunaratne P, Donnelly L, Mateen BA, Sattar N, Holman RR, Bowden J, Hattersley AT, Pearson ER, Jones AG, Shields BM, McKinley TJ, Dennis JM. Phenotype-based targeted treatment of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes. Diabetologia 2024; 67:822-836. [PMID: 38388753 PMCID: PMC10955037 DOI: 10.1007/s00125-024-06099-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 01/04/2024] [Indexed: 02/24/2024]
Abstract
AIMS/HYPOTHESIS A precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely to benefit. We aimed to use the recently developed Bayesian causal forest (BCF) method to develop and validate an individualised treatment selection algorithm for two major type 2 diabetes drug classes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA). METHODS We designed a predictive algorithm using BCF to estimate individual-level conditional average treatment effects for 12-month glycaemic outcome (HbA1c) between SGLT2i and GLP1-RA, based on routine clinical features of 46,394 people with type 2 diabetes in primary care in England (Clinical Practice Research Datalink; 27,319 for model development, 19,075 for hold-out validation), with additional external validation in 2252 people with type 2 diabetes from Scotland (SCI-Diabetes [Tayside & Fife]). Differences in glycaemic outcome with GLP1-RA by sex seen in clinical data were replicated in clinical trial data (HARMONY programme: liraglutide [n=389] and albiglutide [n=1682]). As secondary outcomes, we evaluated the impacts of targeting therapy based on glycaemic response on weight change, tolerability and longer-term risk of new-onset microvascular complications, macrovascular complications and adverse kidney events. RESULTS Model development identified marked heterogeneity in glycaemic response, with 4787 (17.5%) of the development cohort having a predicted HbA1c benefit >3 mmol/mol (>0.3%) with SGLT2i over GLP1-RA and 5551 (20.3%) having a predicted HbA1c benefit >3 mmol/mol with GLP1-RA over SGLT2i. Calibration was good in hold-back validation, and external validation in an independent Scottish dataset identified clear differences in glycaemic outcomes between those predicted to benefit from each therapy. Sex, with women markedly more responsive to GLP1-RA, was identified as a major treatment effect modifier in both the UK observational datasets and in clinical trial data: HARMONY-7 liraglutide (GLP1-RA): 4.4 mmol/mol (95% credible interval [95% CrI] 2.2, 6.3) (0.4% [95% CrI 0.2, 0.6]) greater response in women than men. Targeting the two therapies based on predicted glycaemic response was also associated with improvements in short-term tolerability and long-term risk of new-onset microvascular complications. CONCLUSIONS/INTERPRETATION Precision medicine approaches can facilitate effective individualised treatment choice between SGLT2i and GLP1-RA therapies, and the use of routinely collected clinical features for treatment selection could support low-cost deployment in many countries.
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Affiliation(s)
- Pedro Cardoso
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Katie G Young
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Anand T N Nair
- Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Rhian Hopkins
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Andrew P McGovern
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Eram Haider
- Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Piyumanga Karunaratne
- Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Louise Donnelly
- Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Bilal A Mateen
- Institute of Health Informatics, University College London, London, UK
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Rury R Holman
- Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
- Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK
| | - Jack Bowden
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Andrew T Hattersley
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Ewan R Pearson
- Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Angus G Jones
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Beverley M Shields
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Trevelyan J McKinley
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK
| | - John M Dennis
- Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK.
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16
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Talay L, Vickers M, Loftus S. Why People with Overweight and Obesity Are Seeking Care Through Digital Obesity Services: A Qualitative Analysis of Patients from Australia’s Largest Digital Obesity Provider. TELEMEDICINE REPORTS 2024; 5:187-194. [DOI: 10.1089/tmr.2024.0031] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Louis Talay
- University of Sydney, Faculty of Arts and Social Sciences,Sydney, Australia
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17
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Davidson MB, Davidson SJ, Duran P. Beneficial Effect of Remote Glucose Monitoring and Computerized Insulin Dose Adjustment Algorithms Independent of Insulin Dose Increases in Sizeable Minorities of Patients. Clin Diabetes 2023; 42:364-370. [PMID: 39015160 PMCID: PMC11247028 DOI: 10.2337/cd23-0066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/18/2024]
Abstract
This article describes a program through which interactions every 2-3 weeks between patients and primary care clinicians (PCCs), with recommendations based on analysis of remote glucose monitoring by computerized insulin dose adjustment algorithms, significantly improved diabetes control. Insulin doses increased by 30% in the majority of patients. A sizeable minority (36%) had a decrease or no increase in insulin doses, but still showed an improvement in diabetes control. Frequent interactions allowed PCCs the opportunity to recognize and address medication nonadherence.
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Affiliation(s)
- Mayer B. Davidson
- Charles R. Drew University, Los Angeles, CA
- Mellitus Health, Inc., Los Angeles, CA
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18
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Zhang Z, Zhang Q, Tan Y, Chen Y, Zhou X, Liu S, Yu J. GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis. Front Endocrinol (Lausanne) 2023; 14:1149328. [PMID: 37484944 PMCID: PMC10359616 DOI: 10.3389/fendo.2023.1149328] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 06/14/2023] [Indexed: 07/25/2023] Open
Abstract
Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework. Results 64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center. Conclusion Dulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346, identifier CRD42022359346.
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Affiliation(s)
- Ziqi Zhang
- Department of Endocrinology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China
- The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Qiling Zhang
- Department of Endocrinology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China
- The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Ying Tan
- Department of Endocrinology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China
- The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yu Chen
- Department of Endocrinology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China
- The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiqiao Zhou
- Department of Endocrinology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Su Liu
- Department of Endocrinology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Jiangyi Yu
- Department of Endocrinology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China
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19
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Baryakova TH, Pogostin BH, Langer R, McHugh KJ. Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems. Nat Rev Drug Discov 2023; 22:387-409. [PMID: 36973491 PMCID: PMC10041531 DOI: 10.1038/s41573-023-00670-0] [Citation(s) in RCA: 134] [Impact Index Per Article: 67.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2023] [Indexed: 03/29/2023]
Abstract
Poor medication adherence is a pervasive issue with considerable health and socioeconomic consequences. Although the underlying reasons are generally understood, traditional intervention strategies rooted in patient-centric education and empowerment have proved to be prohibitively complex and/or ineffective. Formulating a pharmaceutical in a drug delivery system (DDS) is a promising alternative that can directly mitigate many common impediments to adherence, including frequent dosing, adverse effects and a delayed onset of action. Existing DDSs have already positively influenced patient acceptability and improved rates of adherence across various disease and intervention types. The next generation of systems have the potential to instate an even more radical paradigm shift by, for example, permitting oral delivery of biomacromolecules, allowing for autonomous dose regulation and enabling several doses to be mimicked with a single administration. Their success, however, is contingent on their ability to address the problems that have made DDSs unsuccessful in the past.
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Affiliation(s)
| | | | - Robert Langer
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Kevin J McHugh
- Department of Bioengineering, Rice University, Houston, TX, USA.
- Department of Chemistry, Rice University, Houston, TX, USA.
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Adherence to Oral Antidiabetic Drugs in Patients with Type 2 Diabetes: Systematic Review and Meta-Analysis. J Clin Med 2023; 12:jcm12051981. [PMID: 36902770 PMCID: PMC10004070 DOI: 10.3390/jcm12051981] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 02/27/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Poor adherence to oral antidiabetic drugs (OADs) in patients with type 2 diabetes (T2D) can lead to therapy failure and risk of complications. The aim of this study was to produce an adherence proportion to OADs and estimate the association between good adherence and good glycemic control in patients with T2D. We searched in MEDLINE, Scopus, and CENTRAL databases to find observational studies on therapeutic adherence in OAD users. We calculated the proportion of adherent patients to the total number of participants for each study and pooled study-specific adherence proportions using random effect models with Freeman-Tukey transformation. We also calculated the odds ratio (OR) of having good glycemic control and good adherence and pooled study-specific OR with the generic inverse variance method. A total of 156 studies (10,041,928 patients) were included in the systematic review and meta-analysis. The pooled proportion of adherent patients was 54% (95% confidence interval, CI: 51-58%). We observed a significant association between good glycemic control and good adherence (OR: 1.33; 95% CI: 1.17-1.51). This study demonstrated that adherence to OADs in patients with T2D is sub-optimal. Improving therapeutic adherence through health-promoting programs and prescription of personalized therapies could be an effective strategy to reduce the risk of complications.
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Ruan Z, Jiang Y, Shi H, Jia R, Ung COL, Hu H. Real-world clinical effectiveness of once-weekly semaglutide in patients with type 2 diabetes: a systematic literature review. Expert Rev Clin Pharmacol 2023; 16:161-176. [PMID: 36706368 DOI: 10.1080/17512433.2023.2174099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
INTRODUCTION The efficacy of once-weekly (O.W.) semaglutide for the treatment of type 2 diabetes mellitus (T2DM) has been demonstrated in clinical trials. The aim of this systematic literature review was to summarize real-world evidence for O.W. semaglutide. METHODS A comprehensive search of PubMed, Web of Science, Embase, and Scilit databases was performed from January 2017 to June 2022 to identify eligible real-world studies examining O.W. semaglutide in T2DM. RESULTS Thirty-one records (18 full-text and 13 abstracts) were identified. The general characteristics of studies and included patients were summarized. Changes in glycated hemoglobin (HbA1c) and body weight were analyzed across studies and according to patient characteristics: baseline HbA1c/weight level, GLP-1 RA-naïve/ GLP-1RA-experienced. The effectiveness of O.W. semaglutide compared with dulaglutide, and the dose of O.W. semaglutide in the real world were also summarized. CONCLUSIONS This systematic literature review provided complementary evidence to findings from the clinical trials and provided a more comprehensive picture of the use of O.W. semaglutide in routine clinical practice. Results of the review suggested that O.W. semaglutide therapy was associated with improving glycemic control and weight loss in both T2DM patients naïve to GLP-1RA and those previously treated with other GLP-1RA in routine clinical practice. PROSPERO REGISTRATION CRD42022306164.
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Affiliation(s)
- Zhen Ruan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
| | - Yixuan Jiang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
| | - Honghao Shi
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
| | - Ruxu Jia
- Global Business School for Health, University College London, London, UK
| | - Carolina Oi Lam Ung
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.,Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao SAR, China
| | - Hao Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.,Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao SAR, China
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22
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McCrimmon RJ, Cheng AY, Galstyan G, Djaballah K, Li X, Coudert M, Frias JP. iGlarLixi versus basal plus Rapid-Acting insulin in adults with type 2 diabetes advancing from basal insulin therapy: The SoliSimplify Real-World study. Diabetes Obes Metab 2023; 25:68-77. [PMID: 36123617 PMCID: PMC10087837 DOI: 10.1111/dom.14844] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/10/2022] [Accepted: 08/16/2022] [Indexed: 12/15/2022]
Abstract
AIM For people with suboptimally controlled type 2 diabetes (T2D) on basal insulin (BI), guidelines recommend several treatment advancement options. This study compared the clinical effectiveness of once-daily iGlarLixi versus a multiple-injection BI + rapid acting insulin (RAI) regimen in adults with T2D advancing from BI therapy in real-world clinical practice. MATERIALS AND METHODS Electronic medical records from the Observational Medical Outcomes Partnership (OMOP) database were analysed retrospectively using propensity score matching to compare therapy advancement with iGlarLixi or BI + RAI in US adults ≥18 years with T2D on BI who had ≥1 valid glycated haemoglobin (HbA1c) value at baseline and at the 6-month follow-up. The primary objective was non-inferiority of iGlarLixi to BI + RAI in HbA1c change from baseline to 6 months (margin 0.3%). RESULTS Propensity score matching generated cohorts with balanced baseline characteristics (N = 814 in each group). HbA1c reduction from baseline to 6 months with iGlarLixi was non-inferior to BI + RAI [mean difference (95% confidence interval): 0.1 (-0.1, 0.2)%; one-sided p = .0032]. At 6 months, weight gain was significantly lower with iGlarLixi than with BI + RAI [-0.8 (-1.3, -0.2) kg; two-sided p = .0069]. Achievement of HbA1c <7% without hypoglycaemia and weight gain were similar between groups [odds ratio (95% confidence interval): 1.15 (0.81, 1.63); p = .4280]. Hypoglycaemia was low in both groups, probably because of underreporting. CONCLUSIONS In real-world clinical practice, glycaemic outcomes 6 months after treatment advancement from BI are similar for people with T2D using iGlarLixi versus BI + RAI, with iGlarLixi leading to less weight gain.
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Affiliation(s)
- Rory J. McCrimmon
- Division of Systems Medicine, School of MedicineUniversity of DundeeDundeeUK
| | | | - Gagik Galstyan
- Diabetic Foot DepartmentEndocrinology Research CenterMoscowRussia
| | | | - Xuan Li
- SanofiBridgewaterNew JerseyUSA
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23
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Deng Y, Ghamsari F, Lu A, Yu J, Zhao L, Kho AN. Use of real-world evidence data to evaluate the comparative effectiveness of second-line type 2 diabetes medications on chronic kidney disease. J Clin Transl Endocrinol 2022; 30:100309. [PMID: 36620756 PMCID: PMC9816064 DOI: 10.1016/j.jcte.2022.100309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 05/30/2022] [Accepted: 10/04/2022] [Indexed: 11/06/2022] Open
Abstract
Chronic kidney disease (CKD) is a common complication of type 2 diabetes mellitus (T2DM). Approximately-one-third of patients with T2DM also have CKD. In clinical trial studies, several anti-diabetic medications (ADM) show evidence of preventing the progression of CKD. Biguanides (e.g., metformin) are widely accepted as the first line medication. However, the comparative effectiveness of second line ADMs on CKD outcomes in T2DM is unclear. In addition, results from clinical trials may not generalize into routine clinical practice. In this study, we aimed to investigate the association of second line ADMs with diagnosed incident CKD, CKD hospitalization, and eGFR < 45 mL/min in T2DM patients using real-world data from electronic health records. Our study found that treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors was significantly associated with lower risk of diagnosed CKD incidence in both primary analysis (hazard ratio, 0.43; 95 % CI, [0.22;0.87]; p-value,0.02) and secondary analysis (hazard ratio, 0.42; 95 % CI, [0.19;0.92]; p-value, 0.03) compared to use of Sulfonylureas (SU) as a second-line ADM. However, significant associations were not observed when using eGFR < 45 mL/min as the endpoint. Treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor was significantly associated with lower risk of diagnosed incident CKD (hazard ratio, 0.7; 95 % CI, [0.53;0.96]; p-value, 0.03) and lower risk of CKD hospitalization (hazard ratio, 0.6; 95 % CI, [0.37; 0.96]; p-value, 0.04) in the primary analysis. However, both associations were not significant in the sensitivity analysis. We did not observe significant association between use of glucagon-like peptide 1 receptor agonists (GLP-1RA), Thiazolidinediones (TZD), insulin and diagnosed CKD incidence, hospitalization or eGFR < 45 mL/min compared to use of SU as a second-line ADM.
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Affiliation(s)
- Yu Deng
- Center for Health Information Partnerships, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,Corresponding author at: Center for health information Partnerships (CHIP), Northwestern University Feinberg School of Medicin, 625 N. Michigan Ave, Suite 1500, Chicago, IL 60611, USA.
| | - Farhad Ghamsari
- Dept of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Alice Lu
- Center for Health Information Partnerships, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jingzhi Yu
- Center for Health Information Partnerships, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Lihui Zhao
- Dept. of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Abel N. Kho
- Center for Health Information Partnerships, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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24
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Linawati Y, Kristin E, Prabandari YS, Kristina SA. Exploring the Experiences and Needs of Patients With Type 2 Diabetes Mellitus in Sleman Regency, Yogyakarta, Indonesia: Protocol for a Qualitative Study. JMIR Res Protoc 2022; 11:e37528. [PMID: 36066966 PMCID: PMC9490526 DOI: 10.2196/37528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 06/07/2022] [Accepted: 08/09/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic disease that can cause adverse effects if not managed effectively. The prevalence of T2DM will continue to rise every year, and data from the International Diabetes Federation show that the number of patients diagnosed with T2DM in Indonesia is predicted to increase from 10.3 million in 2017 to 16.7 million in 2045. Managing T2DM properly is a challenge for the patients because they need to implement lifestyle changes that involve the self-monitoring of blood glucose, consuming prescribed medication properly, maintaining a healthy diet, getting sufficient physical training, keeping a healthy sleeping pattern, managing stress properly, and consulting medical professionals regularly. The worldwide intervention for T2DM focuses on self-management education. The varied results in studies about interventions show that no particular intervention method can be regarded as the most effective. In Indonesia, there are limited studies on educational interventions to improve the quality of life and health of patients with T2DM. OBJECTIVE This study aims to explore the experiences and needs of patients with T2DM in Sleman Regency, Yogyakarta, Indonesia, to develop effective self-management education. METHODS The study will use the phenomenology method with purposive sampling to collect data. The inclusion criteria are patients in the Chronic Disease Self-Management Program at the Sleman Regency Public Health Center who are aged ≥18 years, diagnosed with T2DM for more than a year, with hemoglobin A1c levels ≤7.5% and >7.5%, capable of communicating verbally and literate in the Indonesian language, not deaf, and willing to participate. The data collection is based on the Social Cognitive Theory, which involves selecting assessment targets and analyzing personal factors, environment, and behavior that determine the knowledge, attitude, and adherence of persons with T2DM. Researchers will collect the data through in-depth, face-to-face interviews to learn about knowledge, self-efficacy, outcome expectancy, outcome experience, worry, illness belief, treatment belief, diet, physical activity, medicine intake, treatment pattern, support system, as well as ethnic and cultural influences. The results will be taken from unstructured and open-ended questions written in Indonesian according to the interview guidelines. The data analysis process will go through several stages: reading the data thoroughly; coding; sorting the categories; creating the themes; making general descriptions; and presenting the data in charts, narratives, and recorded quotations from the interviews. RESULTS This study received a grant in May 2021 and gained permission from the Medical and Health Research Ethics Committee of Universitas Gadjah Mada, Indonesia, on July 1, 2021. Data collection started on August 12, 2021, and the results are expected to be published in 2022. CONCLUSIONS The results of this study will be used to design an educational intervention model to improve the knowledge, attitude, and adherence of patients with T2DM. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/37528.
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Affiliation(s)
- Yunita Linawati
- Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
| | - Erna Kristin
- Department of Pharmacology, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
| | - Yayi Suryo Prabandari
- Department of Health Behavior, Environment Health & Social Medicine, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
| | - Susi Ari Kristina
- Department of Pharmaceutics, Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia
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25
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Altmann HM, Kazan J, Gebara MA, Blumberger DM, Karp JF, Lenze EJ, Mulsant BH, Reynolds CF, Stahl ST. Predicting Medication Nonadherence in Older Adults With Difficult-to-Treat Depression in the IRL-GRey Randomized Controlled Trial. Am J Geriatr Psychiatry 2022; 30:994-1002. [PMID: 35393165 PMCID: PMC9356982 DOI: 10.1016/j.jagp.2022.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 01/31/2022] [Accepted: 03/04/2022] [Indexed: 11/23/2022]
Abstract
OBJECTIVE Nonadherence to antidepressants interferes with optimal treatment of late-life depression. This analysis examines clinical and treatment factors predicting medication nonadherence in difficult-to-treat late-life depression. METHODS Secondary analysis of data from a clinical trial of antidepressant pharmacotherapy for Major Depressive Disorder in 468 adults aged 60+ years. All participants received venlafaxine XR for 12 weeks. Nonremitters were randomized to augmentation with either aripiprazole or placebo for 12 additional weeks. Medication adherence was assessed 14 times over 24 weeks. The analyses examined sociodemographic, clinical, and treatment factors that may predict antidepressant nonadherence during early (weeks 1-6), late (weeks 7-12), and augmentation (weeks 13--24) treatment. RESULTS Poor cognitive function and early response were predictive of early nonadherence. Poor cognitive function and prior nonadherence were predictive of late nonadherence. Living alone was associated with nonadherence both late and during augmentation treatment. CONCLUSION Future studies should consider the role of early response and cognitive function to improve antidepressant adherence, particularly among older adults who live alone.
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Affiliation(s)
- Helene M Altmann
- Department of Psychiatry (HMA, JK, MAG, CFR, STS), University of Pittsburgh, Pittsburgh, PA
| | - Joseph Kazan
- Department of Psychiatry (HMA, JK, MAG, CFR, STS), University of Pittsburgh, Pittsburgh, PA
| | - Marie Anne Gebara
- Department of Psychiatry (HMA, JK, MAG, CFR, STS), University of Pittsburgh, Pittsburgh, PA
| | - Daniel M Blumberger
- Centre for Addiction and Mental Health, Department of Psychiatry (DMB, BHM), University of Toronto, Toronto, ON, Canada
| | - Jordan F Karp
- Department of Psychiatry, College of Medicine (JFK), University of Arizona, Tucson, AZ
| | - Eric J Lenze
- Department of Psychiatry (EJL), Washington University, St. Louis, MO
| | - Benoit H Mulsant
- Centre for Addiction and Mental Health, Department of Psychiatry (DMB, BHM), University of Toronto, Toronto, ON, Canada
| | - Charles F Reynolds
- Department of Psychiatry (HMA, JK, MAG, CFR, STS), University of Pittsburgh, Pittsburgh, PA
| | - Sarah T Stahl
- Department of Psychiatry (HMA, JK, MAG, CFR, STS), University of Pittsburgh, Pittsburgh, PA.
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26
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Li G, Zhang J, Van Spall HGC, Douglas PS, Wang Y, Sun X, Thabane L. Exploring ethnic representativeness in diabetes clinical trial enrolment from 2000 to 2020: a chronological survey. Diabetologia 2022; 65:1461-1472. [PMID: 35705796 PMCID: PMC9200441 DOI: 10.1007/s00125-022-05736-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 04/07/2022] [Indexed: 02/05/2023]
Abstract
AIMS/HYPOTHESIS Ethnic representativeness of participant enrolment in diabetes RCTs involving multiple ethnicities remains unknown. The aims of this study were to evaluate the status and temporal trend of ethnic representativeness in enrolment to diabetes RCTs, and to assess under-enrolment of non-white ethnic groups and explore trial characteristics associated with under-enrolment. METHODS We conducted a chronological survey by systematically searching the literature to include eligible RCTs published between January 2000 and December 2020. We assessed temporal trends in enrolment of ethnic groups in the included trials. Univariable logistic regression was used to explore the association between trial characteristics and under-enrolment of non-white groups, using a participant to prevalence ratio of <0.8 to define under-enrolment. This study was registered in PROSPERO (CRD42021229100). RESULTS We included 405 RCTs for analysis (327 multi-country trials, 69 conducted in the USA and nine conducted in the UK). The median enrolment rate of all non-white groups was 24.0% in the overall RCTs. Trials conducted in the USA and the UK had median enrolment rates of 29.0% and 12.0% for all non-white groups, respectively. There was a temporal trend towards increased participation of non-white ethnic groups in the overall RCTs; however, no significant improvement over time was found in the US or UK trials. Non-white groups were under-enrolled in most included trials: 62.3% (43/69) in US trials and 77.8% (7/9) in UK trials. The US trials with a high female proportion were associated with lower odds of under-enrolment of all non-white groups (OR 0.22; 95% CI 0.07, 0.65), while trials receiving funding from industry showed increased odds of under-enrolment (OR 4.64; 95% CI 1.50, 14.35). Outpatient enrolment and intervention duration were significantly associated with under-enrolment of Black participants. Only a small proportion of trials reported subgroup results or explored the effect modification by ethnicity. CONCLUSIONS/INTERPRETATION A temporal trend towards increased non-white ethnic enrolment was found in diabetes RCTs globally, but not in the USA or the UK. Non-white ethnic groups were under-represented in the majority of diabetes trials conducted in the USA and the UK. Some trial characteristics may be associated with non-white under-enrolment in diabetes trials. These findings provide some evidence for non-white ethnic representativeness in diabetes trials over the past two decades, and highlight the need for more effective strategies and endeavours to alleviate under-enrolment of non-white ethnic groups.
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Affiliation(s)
- Guowei Li
- Center for Clinical Epidemiology and Methodology, Guangdong Second Provincial General Hospital, Guangzhou, China.
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
| | - Jingyi Zhang
- Center for Clinical Epidemiology and Methodology, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Harriette G C Van Spall
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Pamela S Douglas
- Duke University Clinical Research Institute, Duke University, Durham, NC, USA
| | - Yaoyao Wang
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Xin Sun
- Chinese Evidence-Based Medicine Center and Cochrane China Center, West China Hospital, Sichuan University, Chengdu, China.
| | - Lehana Thabane
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
- St Joseph's Healthcare Hamilton, Hamilton, ON, Canada
- Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
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Lawrence DS, Ssali A, Moshashane N, Nabaggala G, Maphane L, Harrison TS, Meya DB, Jarvis JN, Seeley J. Decision making in a clinical trial for a life-threatening illness: Therapeutic expectation, not misconception. Soc Sci Med 2022; 305:115082. [PMID: 35649301 DOI: 10.1016/j.socscimed.2022.115082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 05/22/2022] [Accepted: 05/23/2022] [Indexed: 01/10/2023]
Abstract
Potential participants for clinical trials which aim to define treatments for life-threatening conditions are often extremely unwell. When exploring why individuals participate in clinical trials one common observation is a misplaced expectation of personal benefit - a therapeutic misconception. The care offered in some clinical trials is of a higher standard than is routinely available and this has led to criticism around the freedom of choice to enrol - structural coercion. We embedded an ethnographic study within a randomised controlled trial for HIV-associated cryptococcal meningitis in Gaborone, Botswana and Kampala, Uganda. We aimed to gain an understanding of decision-making around the trial and how this was impacted by the study design and broader social context. We conducted in-depth interviews with trial participants, surrogate decision makers and researchers, combined these with direct observations and analysed data using thematic analysis. Between January 2020 and June 2021 we interviewed 89 individuals. We found previous exposure to and awareness of clinical research was limited, as was understanding of the trial objectives and design. Through observations and engagement with healthcare facilities decision-makers were able to identify the trial as providing the best possible chance of survival. Hesitation and reluctance were mostly due to fear of lumbar punctures which was sometimes based on rumours but often based on tragic personal experience. Despite fear, and sometimes conviction that they would die, individuals agreed to consent, often against the wishes of family members. Reassurance and confidence came from trust in routine care staff and the research team but also from fellow participants and their surrogates. We argue that participants made informed decisions based on a therapeutic expectation from the trial and that rather than being the result of structural coercion this was an informed and voluntary choice.
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Affiliation(s)
- David S Lawrence
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
| | - Agnes Ssali
- Social Aspects of Health Programme, MRC/UVRI & LSHTM Uganda Research Institute, Entebbe, Uganda; Department of Global Health and Development, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, UK
| | - Neo Moshashane
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana
| | - Georgina Nabaggala
- Social Aspects of Health Programme, MRC/UVRI & LSHTM Uganda Research Institute, Entebbe, Uganda
| | | | - Thomas S Harrison
- Institute of Infection and Immunity, St George's University London, London, UK; Clinical Academic Group in Infection and Immunity, St George's University Hospitals NHS Foundation Trust, London, UK; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK
| | - David B Meya
- Infectious Diseases Institute, Makerere University, Kampala, Uganda
| | - Joseph N Jarvis
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana
| | - Janet Seeley
- Social Aspects of Health Programme, MRC/UVRI & LSHTM Uganda Research Institute, Entebbe, Uganda; Department of Global Health and Development, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, UK
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28
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Sethi B, Al-Rubeaan K, Unubol M, Mabunay MA, Berthou B, Pilorget V, Vethakkan SR, Frechtel G. Efficacy and Safety of Insulin Glargine 300 U/mL in People with Type 2 Diabetes Uncontrolled on Basal Insulin: The 26-Week Interventional, Single-Arm ARTEMIS-DM Study. Diabetes Ther 2022; 13:1395-1408. [PMID: 35713873 PMCID: PMC9205141 DOI: 10.1007/s13300-022-01271-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 05/09/2022] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION The efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa. METHODS The ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5-10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed. RESULTS A total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (- 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event. CONCLUSION In people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions. CLINICALTRIALS GOV IDENTIFIER NCT03760991.
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Affiliation(s)
| | - Khalid Al-Rubeaan
- Research and Scientific Center Sultan Bin Abdulaziz Humanitarian City, Riyadh, Saudi Arabia
| | - Mustafa Unubol
- Faculty of Medicine, Aydın Adnan Menderes University, Aydın, Turkey
| | | | | | | | | | - Gustavo Frechtel
- Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, Argentina
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29
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Gao B, Gao W, Wan H, Xu F, Zhou R, Zhang X, Ji Q. Efficacy and safety of alogliptin versus acarbose in Chinese type 2 diabetes patients with high cardiovascular risk or coronary heart disease treated with aspirin and inadequately controlled with metformin monotherapy or drug-naive: A multicentre, randomized, open-label, prospective study (ACADEMIC). Diabetes Obes Metab 2022; 24:991-999. [PMID: 35112779 PMCID: PMC9314577 DOI: 10.1111/dom.14661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 01/18/2022] [Accepted: 01/31/2022] [Indexed: 11/29/2022]
Abstract
AIMS To demonstrate the noninferiority of alogliptin to acarbose, in terms of antidiabetic efficacy, in Chinese people with uncontrolled type 2 diabetes (T2D) and high cardiovascular risk. MATERIALS AND METHODS ACADEMIC (NCT03794336) was a randomized, open-label, phase IV study conducted at 46 sites in China. Antidiabetic treatment-naive or metformin-treated adults with uncontrolled T2D (glycated haemoglobin [HbA1c] 58.0-97.0 mmol/mol) were randomized 2:1 to alogliptin 25 mg once daily or acarbose 100 mg three times daily for 16 weeks. All participants had a documented history of coronary heart disease or high cardiovascular risk at screening and received aspirin (acetylsalicylic acid) 100 mg daily throughout the trial. The primary endpoints were change in HbA1c versus baseline, and the incidence of gastrointestinal adverse events (AEs). Safety and tolerability were also assessed. RESULTS A total of 1088 participants were randomized. Alogliptin was noninferior to acarbose for the change in Week-16 HbA1c (least-squares mean change [standard error] -11.9 [0.4] vs. -11.4 [0.5] mmol/mol, respectively; difference between arms -0.5 [0.7] mmol/mol; 95% confidence interval -1.9 to 0.8 mmol/mol), and was associated with a lower incidence of gastrointestinal AEs (8.9% vs. 33.6%, respectively; P < 0.0001). More alogliptin than acarbose recipients achieved HbA1c <53.0 mmol/mol without gastrointestinal AEs (48.0% vs. 32.7%; P < 0.0001). Discontinuations due to treatment-related AEs were less frequent with alogliptin than acarbose (0.3% vs. 2.5%). CONCLUSIONS Glycaemic control was comparable between alogliptin and acarbose, but the gastrointestinal tolerability of alogliptin was better. More patients achieved target HbA1c without gastrointestinal AEs with alogliptin, suggesting that this agent may be preferred in clinical practice.
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Affiliation(s)
- Bin Gao
- Air Force Military Medical University Tangdu HospitalXi’anChina
- Air Force Military Medical University Xijing HospitalXi’anChina
| | - Weiguo Gao
- Qingdao Endocrinology and Diabetes HospitalQingdaoChina
| | | | - Fengmei Xu
- Hebi Coal Industry Co. Ltd. General HospitalHebiChina
| | | | | | - Qiuhe Ji
- Air Force Military Medical University Xijing HospitalXi’anChina
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Terauchi Y, Usami M, Inoue T. The Durable Safety and Effectiveness of Lixisenatide in Japanese People with Type 2 Diabetes: The Post-Marketing Surveillance PRANDIAL Study. Adv Ther 2022; 39:2873-2888. [PMID: 35449321 PMCID: PMC9122860 DOI: 10.1007/s12325-022-02121-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/09/2022] [Indexed: 11/30/2022]
Abstract
Introduction Real-world evidence on lixisenatide in Japanese people with type 2 diabetes (T2D) is lacking. Therefore, the 3-year post-marketing PRANDIAL study was conducted to evaluate the safety (primary objective) and effectiveness (secondary objective) of lixisenatide in Japanese people with T2D during routine clinical practice. Methods This prospective, observational, multicenter, open-label study was conducted in Japanese individuals with T2D who initiated lixisenatide treatment between March 2014 and June 2017. Using electronic case report forms, investigators collected baseline demographic and clinical information and data on medications, safety and effectiveness up to 3 years after initiation of lixisenatide. Results Overall, 3046 participants were analyzed; their mean ± standard deviation (SD) age was 58.9 ± 13.1 years, and 53.7% were male. Mean ± SD duration of T2D was 12.8 ± 8.6 years, and baseline glycated hemoglobin (HbA1c) was 8.7% ± 1.7%. Most participants (93.9%) were receiving concomitant antidiabetic medications when they initiated lixisenatide. Median (range) lixisenatide treatment duration was 382 (1–1096) days. Adverse drug reactions (ADRs) were reported in 604 participants (19.8%) and serious ADRs in 22 (0.7%). The most common ADR was nausea (9.0%). Of ADRs of special interest, hypoglycemia occurred in 2.9% of participants, injection site reactions in 0.9%, and hypoglycemic unconsciousness in 0.03%. Baseline characteristics associated with an increased risk of ADRs (p < 0.05) were history of treatment for cardiovascular disease, hepatic dysfunction, and other complications. Effectiveness was analyzed in 2675 participants; HbA1c, fasting plasma glucose, postprandial glucose, and body weight all decreased significantly at last observation (all p < 0.0001 vs. baseline). Conclusions Lixisenatide was well tolerated, with no unexpected ADRs or new safety signals identified, and showed effective glycemic control and weight reduction up to 3 years, supporting the use of lixisenatide as a safe and effective treatment option for T2D in routine clinical practice in Japan. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02121-5. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are antidiabetic drugs that lower blood glucose levels by stimulating the release of insulin and suppressing glucagon, the key hormones involved in controlling blood glucose levels in the body. The selective GLP-1RA lixisenatide was approved for the management of adults with type 2 diabetes (T2D) in Japan based on data from randomized clinical trials. However, these studies may not be representative of the safety and effectiveness of the drug when used in routine clinical practice. Therefore, we conducted the 3-year post-marketing PRANDIAL study to assess the safety and effectiveness of lixisenatide in 3046 Japanese individuals with T2D who started the drug between March 2014 and June 2017. Adverse drug reactions (adverse events for which lixisenatide causality could not be excluded) occurred in 19.8% of participants, with the most common adverse drug reaction being nausea. Hypoglycemia (abnormally low blood glucose levels) was reported in 2.9%. Individuals with a history of treatment for cardiovascular disease, hepatic dysfunction, and other complications had an increased risk of adverse drug reactions. Lixisenatide provided significant improvements in blood glucose control, with significant decreases in glycated hemoglobin (a marker of blood glucose control), fasting plasma glucose, and postprandial glucose levels from baseline, as well as significant reductions in body weight. In this real-world post-marketing surveillance study, lixisenatide was well tolerated, raising no new safety concerns, and provided durable effective blood glucose control and weight reduction. These results support the use of lixisenatide in Japanese individuals with T2D in routine clinical practice.
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Affiliation(s)
- Yasuo Terauchi
- Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
| | - Makiko Usami
- Post-Authorization Regulatory Studies, Sanofi K.K., Opera City Tower, 3-20-2 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 163-1488, Japan.
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Smith K, Taylor GS, Brunsgaard LH, Walker M, Bowden Davies KA, Stevenson EJ, West DJ. Thrice daily consumption of a novel, premeal shot containing a low dose of whey protein increases time in euglycemia during 7 days of free-living in individuals with type 2 diabetes. BMJ Open Diabetes Res Care 2022; 10:10/3/e002820. [PMID: 35618446 PMCID: PMC9137348 DOI: 10.1136/bmjdrc-2022-002820] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 05/06/2022] [Indexed: 01/25/2023] Open
Abstract
INTRODUCTION During acute feeding trials, consuming a large dose of whey protein (WP) before meals improves postprandial glucose regulation in people with type 2 diabetes. It is unclear if the reported benefits of premeal WP supplementation are translatable to everyday care or are associated with clinically meaningful, real-world glycemic outcomes. This study examined the application of a novel, premeal shot containing a low dose of WP on parameters of free-living glycemic control in people with type 2 diabetes. RESEARCH DESIGN AND METHODS In a randomized, placebo-controlled, single-blind crossover design, 18 insulin naive individuals with type 2 diabetes ((mean±SD) age, 50±6 years; HbA1c (glycated hemoglobin), 7.4%±0.8%; duration of diabetes, 6±5 years) consumed a ready-to-drink WP shot (15 g of protein) or a nutrient-depleted placebo beverage 10 min before breakfast, lunch, and dinner over a 7-day free-living period. Free-living glucose control was measured by blinded continuous glucose monitoring and determined by the percentage of time spent above range (>10 mmol/L), in euglycemic range (3.9-10.0 mmol/L), below range (<3.9 mmol/L) and mean glucose concentrations. RESULTS Mealtime WP supplementation reduced the prevalence of daily hyperglycemia by 8%±19% (30%±25% vs 38%±28%, p<0.05), thereby enabling a 9%±19% (~2 hours/day) increase in the time spent in euglycemia (p<0.05). Mean 24-hour blood glucose concentrations were 0.6±1.2 mmol/L lower during WP compared with placebo (p<0.05). Similar improvements in glycemic control were observed during the waken period with premeal WP supplementation (p<0.05), whereas nocturnal glycemic control was unaffected (p>0.05). Supplemental compliance/acceptance was high (>98%), and no adverse events were reported. CONCLUSIONS Consuming a novel premeal WP shot containing 15 g of protein before each main meal reduces the prevalence of daily hyperglycemia, thereby enabling a greater amount of time spent in euglycemic range per day over 7 days of free-living in people with type 2 diabetes. TRIAL REGISTRATION NUMBER ISRCTN17563146; www.isrctn.com/ISRCTN17563146.
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Affiliation(s)
- Kieran Smith
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Guy S Taylor
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Lise H Brunsgaard
- Health and Performance Nutrition, Arla Foods Ingredients Group P/S, Viby J, Denmark
| | - Mark Walker
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Kelly A Bowden Davies
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
- Sport and Exercise Sciences, Manchester Metropolitan University, Manchester, UK
| | - Emma J Stevenson
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Daniel J West
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
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Gao Q, Tan NC, Fang HSA, Lee ML, Hsu W. Glycaemic control of Asian patients with type-2 diabetes mellitus on tiered up-titration of metformin monotherapy: A one-year real-world retrospective longitudinal study in primary care. Diabetes Res Clin Pract 2022; 187:109874. [PMID: 35436547 DOI: 10.1016/j.diabres.2022.109874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/26/2022] [Accepted: 04/11/2022] [Indexed: 11/27/2022]
Abstract
AIMS To determine the glycaemic control and associated factors among patients with type-2 diabetes mellitus on tiered metformin monotherapy over one-year. METHODS Adult Asian patients on metformin monotherapy with tiered dosage up-titration (low < 500 mg/day; medium 500-<1000 mg/day and high ≥ 1000 mg/day) are divided into four sub-cohorts based on their baseline HbA1c < 7%(C<7); 7%-<8%(C7-<8); 8%-<9%(C8-<9) and ≥ 9%(C≥9). The HbA1c absolute reduction, time to reach glycaemic control (HbA1c < 7%), and time from glycaemic control to failure (HbA1c ≥ 7%) after the dosage up-titration were the outcomes. RESULTS Among 5503 eligible patients (mean age = 64.9 years, 45.6% males and 74.6% Chinese), the HbA1c absolute reduction after the up-titration at three months are 0%, 0.4%-0.6%, 0.8%-1.2% and 2.0%-2.1% for C<7, C7-<8, C8-<9 and C≥9 respectively. The median time (months) to attain glycaemic control for low, medium and high dosage up-titration were 4, 3, 3(C7-<8); 12, 7, 4(C8-<9); NA, 7, 7(C≥9). Within twelve months after the goal attainment, 36.2%(C<7), 48.8%(C7-<8), 52.7%(C8-<9) and 45.3%(C≥9) of patients had treatment failure. CONCLUSIONS The results show that the baseline HbA1c and tiered metformin dosage up-titration are associated with disproportionate HbA1c reduction, time to glycaemic control and time from glycaemic control to failure.
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Affiliation(s)
- Qiao Gao
- Institute of Data Science, National University of Singapore, Singapore.
| | - Ngiap Chuan Tan
- SingHealth Polyclinics, Singapore; SingHealth-Duke NUS Family Medicine Academic Clinical Programme, Singapore
| | | | - Mong Li Lee
- Institute of Data Science, National University of Singapore, Singapore; School of Computing, National University of Singapore, Singapore
| | - Wynne Hsu
- Institute of Data Science, National University of Singapore, Singapore; School of Computing, National University of Singapore, Singapore
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Yaguchi Y, Fujihara K, Yamada MH, Matsubayashi Y, Yamada T, Iwanaga M, Kitazawa M, Yamamoto M, Seida H, Kodama S, Sone H. Impact of Medication Adherence and Glycemic Control on the Risk of Micro- and Macrovascular Diseases in Patients with Diabetes. Am J Med 2022; 135:461-470.e1. [PMID: 34798099 DOI: 10.1016/j.amjmed.2021.10.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 09/18/2021] [Accepted: 10/11/2021] [Indexed: 11/26/2022]
Abstract
PURPOSE Our purpose in the research was to clarify the impact of medication adherence to oral hypoglycemic agents during a 1-year period and subsequent glycemic control on the risk of micro- and macrovascular diseases. METHODS Examined was a nationwide claims database on 13,256 individuals with diabetic eye disease without requiring prior treatment, 7,862 without prior initiation of dialysis, 15,556 without prior coronary artery disease, 16,243 without prior cerebrovascular disease, and 19,386 without prior heart failure from 2008 to 2016 in Japan. Medication adherence was evaluated by the proportion of days covered. Patients were considered to have poor adherence if the proportion of days covered was <80%. Multivariate Cox regression model identified risks of micro- and macrovascular diseases. RESULTS In each group, mean age was 53 to 54 years, HbA1c was 7.1% to 7.2%, and median follow-up period was 4.6 to 5.1 years, and the percentage of poor adherence was approximately 30%. During the study period, 532 treatment-requiring diabetic eye disease, 75 dialysis, 389 coronary artery disease, 316 cerebrovascular disease, and 144 heart failure events occurred. Multivariate Cox regression model revealed that the hazard ratio (95% confidence interval) of dialysis in the poor adherence group was 2.04 (1.27-3.30) compared with the good adherence group. The hazard ratios in the poor adherence/poor glycemic control group were 3.34 (2.63-4.24) for treatment-requiring diabetic eye disease, 4.23 (2.17-8.26) for dialysis, 1.69 (1.23-2.31) for coronary artery disease, and 2.08 (1.25-3.48) for heart failure compared with the good adherence/good glycemic control group. CONCLUSIONS Poor medication adherence was an independent risk factor for the initiation of dialysis, suggesting that clinicians must pay close attention to these patients.
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Affiliation(s)
- Yuta Yaguchi
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
| | - Kazuya Fujihara
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan.
| | - Mayuko Harada Yamada
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
| | - Yasuhiro Matsubayashi
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
| | - Takaho Yamada
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
| | - Midori Iwanaga
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
| | - Masaru Kitazawa
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
| | - Masahiko Yamamoto
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
| | | | - Satoru Kodama
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
| | - Hirohito Sone
- Department of Internal Medicine, Niigata University Faculty of Medicine, Niigata, Japan
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Mody R, Manjelievskaia J, Marchlewicz EH, Malik RE, Zimmerman NM, Irwin DE, Yu M. Greater Adherence and Persistence with Injectable Dulaglutide Compared with Injectable Semaglutide at 1-Year Follow-up: Data from US Clinical Practice. Clin Ther 2022; 44:537-554. [PMID: 35264311 DOI: 10.1016/j.clinthera.2022.01.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 12/20/2021] [Accepted: 01/28/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE Greater medication adherence and persistence have been associated with improved glycemic control in patients with type 2 diabetes mellitus. This study compared adherence, persistence, and treatment patterns among patients naïve to glucagon-like peptide 1 receptor agonists initiating once-weekly injectable treatment with dulaglutide versus semaglutide over 6-month (6M) and 12-month (12M) follow-up periods. METHODS This retrospective, observational cohort study used administrative claims data from three IBM MarketScan research databases. Data from adult patients with type 2 diabetes newly initiating treatment with dulaglutide or semaglutide between January 2018 and January 2020 (index date was defined as the earliest fill date), without evidence of glucagon-like peptide 1 receptor agonist use in the 6M baseline period, and with continuous enrollment in the 6M baseline and 6M or 12M follow-up period were included. Dulaglutide initiators were propensity score-matched, in a 1:1 ratio, to semaglutide initiators in each 6M and 12M follow-up cohort (26,284 and 13,837 pairs, respectively). FINDINGS In the matched cohorts, baseline characteristics were balanced; the mean age was 53 years, and 50% of patients were women. Compared to semaglutide initiators, dulaglutide initiators were more adherent (6M, 63.4% vs 47.8%; 12M, 54.4% vs 43.3%; both, P < 0.0001), more persistent on therapy (6M, 72% vs 62%, 12M, 55.5% vs 45.3%, both, P < 0.001), and had more mean days of persistence (6M, 145 vs 132, 12M, 254.3 vs 220.7; both, P < 0.001). IMPLICATIONS At both 6M and 12M follow-up, dulaglutide initiators had significantly greater adherence and greater persistence compared with matched semaglutide initiators.
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Affiliation(s)
- Reema Mody
- Eli Lilly and Company, Indianapolis, Indiana.
| | | | | | | | | | | | - Maria Yu
- Eli Lilly and Company, Indianapolis, Indiana
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Evans M, Engberg S, Faurby M, Fernandes JDDR, Hudson P, Polonsky W. Adherence to and persistence with antidiabetic medications and associations with clinical and economic outcomes in people with type 2 diabetes mellitus: A systematic literature review. Diabetes Obes Metab 2022; 24:377-390. [PMID: 34779107 PMCID: PMC9299643 DOI: 10.1111/dom.14603] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/21/2021] [Accepted: 10/31/2021] [Indexed: 12/28/2022]
Abstract
We designed a systematic literature review to identify available evidence on adherence to and persistence with antidiabetic medication in people with type 2 diabetes (T2D). Electronic screening and congress searches identified real-world noninterventional studies (published between 2010 and October 2020) reporting estimates of adherence to and persistence with antidiabetic medication in adults with T2D, and associations with glycaemic control, microvascular and/or macrovascular complications, hospitalizations and healthcare costs. Ninety-two relevant studies were identified, the majority of which were retrospective and reported US data. The proportions of patients considered adherent (median [range] 51.2% [9.4%-84.3%]) or persistent (median [range] 47.7% [16.9%-94.0%]) varied widely across studies. Multiple studies reported an association between greater adherence/persistence and greater reductions in glycated haemoglobin levels. Better adherence/persistence was associated with fewer microvascular and/or macrovascular outcomes, although there was little consistency across studies in terms of which outcomes were improved. More adherent and more persistent patients were typically less likely to be hospitalized or to have emergency department visits/admissions and spent fewer days in hospital annually than less adherent/persistent patients. Greater adherence and persistence were generally associated with lower hospitalization costs, higher pharmacy costs and lower or budget-neutral total healthcare costs compared with lower adherence/persistence. In conclusion, better adherence and persistence in people with T2D is associated with lower rates of microvascular and/or macrovascular outcomes and inpatient hospitalization, and lower or budget-neutral total healthcare expenditure. Education and treatment strategies to address suboptimal adherence and persistence are needed to improve clinical and economic outcomes.
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Affiliation(s)
- Marc Evans
- Department of Diabetes and EndocrinologyUniversity Hospital LlandoughPenarthUK
| | | | | | | | | | - William Polonsky
- Behavioral Diabetes InstituteSan DiegoCaliforniaUSA
- Department of MedicineUniversity of CaliforniaSan DiegoCaliforniaUSA
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Cardiovascular and Renal Effectiveness of GLP-1 Receptor Agonists vs. Other Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Studies. Metabolites 2022; 12:metabo12020183. [PMID: 35208256 PMCID: PMC8879165 DOI: 10.3390/metabo12020183] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/09/2022] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular outcome trials (CVOT) showed that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) is associated with significant cardiovascular benefits. However, CVOT are scarcely representative of everyday clinical practice, and real-world studies could provide clinicians with more relatable evidence. Here, literature was thoroughly searched to retrieve real-world studies investigating the cardiovascular and renal outcomes of GLP-1RA vs. other glucose-lowering drugs and carry out relevant meta-analyses thereof. Most real-world studies were conducted in populations at low cardiovascular and renal risk. Of note, real-world studies investigating cardio-renal outcomes of GLP-1RA suggested that initiation of GLP-1RA was associated with a greater benefit on composite cardiovascular outcomes, MACE (major adverse cardiovascular events), all-cause mortality, myocardial infarction, stroke, cardiovascular death, peripheral artery disease, and heart failure compared to other glucose-lowering drugs with the exception of sodium-glucose transporter-2 inhibitors (SGLT-2i). Initiation of SGLT-2i and GLP-1RA yielded similar effects on composite cardiovascular outcomes, MACE, stroke, and myocardial infarction. Conversely, GLP-1RA were less effective on heart failure prevention compared to SGLT-2i. Finally, the few real-world studies addressing renal outcomes suggested a significant benefit of GLP-1RA on estimated glomerular filtration rate (eGFR) reduction and hard renal outcomes vs. active comparators except SGLT-2i. Further real-world evidence is needed to clarify the role of GLP-1RA in cardio-renal protection among available glucose-lowering drugs.
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Verhagen C, Janssen J, Biessels GJ, Johansen OE, Exalto LG. Females with type 2 diabetes are at higher risk for accelerated cognitive decline than males: CAROLINA-COGNITION study. Nutr Metab Cardiovasc Dis 2022; 32:355-364. [PMID: 34895804 DOI: 10.1016/j.numecd.2021.10.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 10/02/2021] [Accepted: 10/18/2021] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIM Cognitive dysfunction is increasingly recognized as an important comorbidity of type 2 diabetes (T2D). We aimed to establish if the risk of accelerated cognitive decline (ACD) is higher in females with T2D than males. METHODS AND RESULTS 3163 participants (38% female) with T2D from the cognition substudy of CAROLINA® (NCT01243424) were included (mean age 64.4 ± 9.2 years; T2D duration 7.6 ± 6.1 years). The cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning (Trail Making and Verbal Fluency Test). Potential confounders, were taken into account at an individual patient level. Logistic regression analysis was used to investigate ACD risk by sex. We assessed potential mediators for sex differences in ACD using Causal Mediation Analysis (CMA). After a median follow-up duration of 6.1 ± 0.7 years, 361 (30.0%) females compared to 494 (25.2%) males exhibited ACD (OR 1.27 [95%CI 1.08-1.49], p = .003). Depressive symptoms, which were more common in females (24.3% vs 12.5%), mediated between sex and ACD (mediation effect 20.3%, p = 0.03). There were no other significant mediators. CONCLUSION Females with T2D had a higher risk of ACD compared to males. This was partly explained by depressive symptoms. After evaluation of vascular and diabetes-related risk factors, complications and treatment, a major share of the higher risk of ACD in females remained unexplained. Our results highlight the need for further research on causes of sex-specific ACD in T2D.
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Affiliation(s)
- Chloë Verhagen
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Jolien Janssen
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Geert Jan Biessels
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Odd Erik Johansen
- Cardiometabolic Clinical Development, Nestlé Health Science, Vevey, Switzerland.
| | - Lieza G Exalto
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
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Lee DSU, Lee H. Adherence and persistence rates of major antidiabetic medications: a review. Diabetol Metab Syndr 2022; 14:12. [PMID: 35033161 PMCID: PMC8761325 DOI: 10.1186/s13098-022-00785-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 01/05/2022] [Indexed: 12/15/2022] Open
Abstract
The objective of this paper was to review the adherence and persistence rates of major antidiabetic medication classes (i.e., metformin, sulfonylureas, sodium glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, insulin, glucagon-like peptide-1 receptor agonists, and thiazolidinediones) by summarizing the major findings of the studies published since 2017. In addition, we reported the potential causes for low adherence and persistence of antidiabetic medications. Based on the literature, the highest rate of adherence and persistence was consistently observed in metformin users. Second to metformin were sodium glucose cotransporter-2 inhibitors. Injectable therapies such as insulin and glucagon-like peptide-1 receptor agonists trailed low on the adherence and persistence rates. To the best of our knowledge, no studies published since the year 2017 analyzed the adherence and persistence of thiazolidinediones independently. The most frequently cited cause for low adherence and persistence was the severity of adverse events. Baseline characteristics (e.g., baseline HbA1c level), demographic information (e.g., age, gender, or ethnicity), and comorbidity profiles also had significant impacts on adherence and persistence in patients with type 2 diabetes mellitus.
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Affiliation(s)
- David Seung U Lee
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea
- Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea
| | - Howard Lee
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea.
- Department of Applied Biomedical Engineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea.
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
- Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea.
- Advanced Institute of Convergence Technology, Suwon, 16229, South Korea.
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Davies MJ, Rosenstock J, Ali A, Russell‐Jones D, Souhami E, Palmer K, Ji C, Niemoeller E, Skolnik N. Efficacy of iGlarLixi in adults with type 2 diabetes inadequately controlled (glycated haemoglobin ≥8%, ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the LixiLan-O randomized trial. Diabetes Obes Metab 2022; 24:34-41. [PMID: 34617398 PMCID: PMC9293415 DOI: 10.1111/dom.14543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 08/13/2021] [Accepted: 08/31/2021] [Indexed: 12/01/2022]
Abstract
AIMS To assess the efficacy and safety of iGlarLixi (the titratable fixed-ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol). MATERIALS AND METHODS The LixiLan-O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan-O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening. RESULTS The mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2-hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c -1.9% vs. -1.6% or -1.0% [-20 vs. -17 or -10 mmol/mol; 2-hour PPG -7.2 vs. -4.6 or -5.5 mmol/L). Greater proportions of participants achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi versus iGlar or Lixi (67% vs. 51% or 18%), and the composite endpoints of HbA1c <7% (<53 mmol/mol) with no body weight gain (36% vs. 19% or 16%), and HbA1c <7% (<53 mmol/mol) with no body weight gain and no documented symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L; 28% vs. 15% or 15%). The incidence rates of documented symptomatic hypoglycaemia were 29.0%, 27.9% and 12.1% for iGlarLixi, iGlar and Lixi, respectively. CONCLUSIONS Adults with T2D and HbA1c ≥64 mmol/mol (≥8%) despite two OADs at screening achieved better glycaemic control with iGlarLixi versus iGlar or Lixi, without increased risk of hypoglycaemia versus iGlar.
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Affiliation(s)
- Melanie J. Davies
- Diabetes Research CentreUniversity of Leicester, Leicester General Hospital and University Hospitals of Leicester NHS TrustLeicesterUK
- National Institute of Health ResearchLeicester Biomedical Research CentreLeicesterUK
| | | | - Amar Ali
- Oakenhurst Medical PracticeBlackburnUK
| | | | | | | | | | | | - Neil Skolnik
- Abington Family MedicineJenkintownPennsylvaniaUSA
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Lauffenburger JC, Yom-Tov E, Keller PA, McDonnell ME, Bessette LG, Fontanet CP, Sears ES, Kim E, Hanken K, Buckley JJ, Barlev RA, Haff N, Choudhry NK. REinforcement learning to improve non-adherence for diabetes treatments by Optimising Response and Customising Engagement (REINFORCE): study protocol of a pragmatic randomised trial. BMJ Open 2021; 11:e052091. [PMID: 34862289 PMCID: PMC8647547 DOI: 10.1136/bmjopen-2021-052091] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
INTRODUCTION Achieving optimal diabetes control requires several daily self-management behaviours, especially adherence to medication. Evidence supports the use of text messages to support adherence, but there remains much opportunity to improve their effectiveness. One key limitation is that message content has been generic. By contrast, reinforcement learning is a machine learning method that can be used to identify individuals' patterns of responsiveness by observing their response to cues and then optimising them accordingly. Despite its demonstrated benefits outside of healthcare, its application to tailoring communication for patients has received limited attention. The objective of this trial is to test the impact of a reinforcement learning-based text messaging programme on adherence to medication for patients with type 2 diabetes. METHODS AND ANALYSIS In the REinforcement learning to Improve Non-adherence For diabetes treatments by Optimising Response and Customising Engagement (REINFORCE) trial, we are randomising 60 patients with suboptimal diabetes control treated with oral diabetes medications to receive a reinforcement learning intervention or control. Subjects in both arms will receive electronic pill bottles to use, and those in the intervention arm will receive up to daily text messages. The messages will be individually adapted using a reinforcement learning prediction algorithm based on daily adherence measurements from the pill bottles. The trial's primary outcome is average adherence to medication over the 6-month follow-up period. Secondary outcomes include diabetes control, measured by glycated haemoglobin A1c, and self-reported adherence. In sum, the REINFORCE trial will evaluate the effect of personalising the framing of text messages for patients to support medication adherence and provide insight into how this could be adapted at scale to improve other self-management interventions. ETHICS AND DISSEMINATION This study was approved by the Mass General Brigham Institutional Review Board (IRB) (USA). Findings will be disseminated through peer-reviewed journals, clinicaltrials.gov reporting and conferences. TRIAL REGISTRATION NUMBER Clinicaltrials.gov (NCT04473326).
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Affiliation(s)
- Julie C Lauffenburger
- Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Elad Yom-Tov
- Microsoft Research, Microsoft, Herzeliya, Israel
| | - Punam A Keller
- Tuck School of Business, Dartmouth College, Hanover, NH, USA
| | - Marie E McDonnell
- Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Lily G Bessette
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Constance P Fontanet
- Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Ellen S Sears
- Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Erin Kim
- Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Kaitlin Hanken
- Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - J Joseph Buckley
- Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Renee A Barlev
- Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Nancy Haff
- Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Niteesh K Choudhry
- Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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Pierce SL, Bisson CM, Dubois ME, Grimes SB, Katz MS, Weed MM, Wyatt SN, Eckart EK, Peck JD, Edwards RK. Clinical effectiveness of adding azithromycin to antimicrobial prophylaxis for cesarean delivery. Am J Obstet Gynecol 2021; 225:335.e1-335.e7. [PMID: 34052192 PMCID: PMC8429245 DOI: 10.1016/j.ajog.2021.05.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/11/2021] [Accepted: 05/14/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND A recent large clinical trial demonstrated an approximately 50% decrease in the rate of postoperative infection in women who were laboring and/or had rupture of membranes for >4 hours and who received azithromycin in addition to standard preoperative antibiotic prophylaxis at the time of cesarean delivery. Given these results, our institution made a policy change in May 2017 to add azithromycin to standard preoperative prophylaxis for all cesarean deliveries. OBJECTIVE This study aimed to evaluate the clinical effectiveness of adding azithromycin to preoperative antibiotic prophylaxis for cesarean delivery. STUDY DESIGN We conducted a before-and-after cohort study of women delivered via cesarean delivery at our institution. The preimplementation group included women who delivered from March 1, 2016, to February 28, 2017, (before an institutional practice change of adding azithromycin to standard preoperative prophylaxis), and the postimplementation group included women who delivered from September 1, 2017, to August 31, 2018 (allowing a 6-month period for uptake of the practice change). The primary outcome was a composite of postoperative infections (endometritis, wound infection, other maternal infections). Unadjusted and adjusted risk ratios and 95% confidence intervals were estimated using a modified Poisson regression model. RESULTS In the preimplementation (n=1171) and postimplementation (n=1168) groups, the incidence rates of the composite outcomes were 4.7% and 5.3%, respectively (P=.49). Both unadjusted (relative risk, 1.13; 95% confidence interval, 0.78-1.62) and adjusted (adjusted relative risk, 1.06; 95% confidence interval, 0.74-1.52) comparisons were not significantly different. In addition, results were statistically nonsignificant, but in the direction of lower rates of infection, in the after cohort for women in labor and/or with rupture of membranes for ≥4 hours (relative risk, 0.88 [95% confidence interval, 0.56-1.39]; adjusted relative risk, 0.82 [95% confidence interval, 0.52-1.30]) and for women with clinical chorioamnionitis (relative risk, 0.37 [95% confidence interval, 0.08-1.67]; data too sparse for adjusted analysis). In the subgroup of women who were not in labor, the after cohort had a statistically nonsignificant increased risk of the composite outcome in both unadjusted (relative risk, 1.53; 95% confidence interval, 0.86-2.72) and adjusted (adjusted relative risk, 1.48; 95% confidence interval, 0.83-2.65]) comparisons. CONCLUSION In clinical practice, the addition of azithromycin to standard preoperative antibiotic prophylaxis for cesarean delivery may have an effect size smaller than seen in the large clinical trial prompting this practice change. Extrapolation of this regimen to women not in labor may be ineffective.
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Affiliation(s)
- Stephanie L Pierce
- Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK.
| | - Courtney M Bisson
- Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Molly E Dubois
- Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Sarah B Grimes
- Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Mikaela S Katz
- Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Mary M Weed
- Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Sabrina N Wyatt
- Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Erin K Eckart
- Department of Biostatistics and Epidemiology, University of Oklahoma Health Science Center, Hudson College of Public Health, Oklahoma City, OK
| | - Jennifer D Peck
- Department of Biostatistics and Epidemiology, University of Oklahoma Health Science Center, Hudson College of Public Health, Oklahoma City, OK
| | - Rodney K Edwards
- Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK
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Fernando K, Bain SC, Holmes P, Jones PN, Patel DC. Glucagon-Like Peptide 1 Receptor Agonist Usage in Type 2 Diabetes in Primary Care for the UK and Beyond: A Narrative Review. Diabetes Ther 2021; 12:2267-2288. [PMID: 34309808 PMCID: PMC8312211 DOI: 10.1007/s13300-021-01116-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 07/07/2021] [Indexed: 11/23/2022] Open
Abstract
The scientific landscape of treatments for type 2 diabetes (T2D) has changed rapidly in the last decade with newer treatments becoming available. However, a large proportion of people with T2D are not able to achieve glycaemic goals because of clinical inertia. The majority of T2D management is in primary care, where clinicians (medical, nursing and pharmacist staff) play an important role in addressing patient needs and achieving treatment goals. However, management of T2D is challenging because of the heterogeneity of T2D and complexity of comorbidity, time constraints, guidance overload and the evolving treatments. Additionally, the current coronavirus disease pandemic poses additional challenges to the management of chronic diseases such as T2D, including routine access to patients for monitoring and communication. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a class of agents that have evolved rapidly in recent years. These agents act in a glucose-dependent manner to promote insulin secretion and inhibit glucagon secretion, as well as enhancing satiety and reducing hunger. As a result, they are effective treatment options for people with T2D, achieving glycated haemoglobin reductions, weight loss and potential cardiovascular benefit, as monotherapy or as add-on to other glucose-lowering therapies. However, given the complexity of managing T2D, it is important to equip primary care clinicians with clear information regarding efficacy, safety and appropriate positioning of GLP-1 RA therapies in clinical practice. This review provides a summary of clinical and real-world evidence along with practical guidance, with the aim of aiding primary care clinicians in the initiation and monitoring of GLP-1 RAs to help ensure that desired outcomes are realised. Furthermore, a benefit/risk tool has been developed on the basis of current available evidence and guidelines to support primary care clinicians in selecting individuals who are most likely to benefit from GLP-1 RA therapies, in addition to indicating clinical situations where caution is needed.
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Affiliation(s)
- Kevin Fernando
- North Berwick Health Centre, North Berwick Group Practice, 54 St. Baldred's Road, North Berwick, EH39 4PU, UK.
| | | | | | | | - Dipesh C Patel
- University College London, Royal Free Campus, London, UK
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Vlacho B, Mata-Cases M, Mundet-Tudurí X, Vallès-Callol JA, Real J, Farre M, Cos X, Khunti K, Mauricio D, Franch-Nadal J. Analysis of the Adherence and Safety of Second Oral Glucose-Lowering Therapy in Routine Practice From the Mediterranean Area: A Retrospective Cohort Study. Front Endocrinol (Lausanne) 2021; 12:708372. [PMID: 34335477 PMCID: PMC8318034 DOI: 10.3389/fendo.2021.708372] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 06/29/2021] [Indexed: 01/23/2023] Open
Abstract
The aims of our study was compare adherence measured by the medical possession ratio (MPR), time until discontinuation and describe adverse events after adding a DPP-4i, SGLT-2i, or sulfonylureas (SU) to metformin in a primary care population with insufficient glycemic control. We used routinely-collected health data from the SIDIAP database. The included subjects were matched by propensity score. The follow-up period was up to 24 months or premature discontinuation. The primary outcomes were the percentage of subjects with good adherence, treatment discontinuation and adverse events among treatment groups. The proportion of patients with good adherence (MPR> 0.8) after the addition of DPP-4i, SGLT-2i or SU was 53.6%, 68.7%, and 43.0%, respectively. SGLT-2i users were 1.7 times more likely to achieve good adherence compared with DPP-4i users (odds ratio [OR]:1.72, 98% confidence interval [CI]:1.51, 1.96), and 2.8 times more likely compared with SU users (OR: 0.35, 98% CI: 0.07, 0.29). The discontinuation hazard ratios were 1.43 (98%CI: 1.26; 1.62) and 1.60 (98%CI: 1.42; 1.81) times higher among SGLT-2i and SU users than DPP-4i users during the follow-up period. No differences were observed for adverse events among the treatment groups. In conclusion, in our real-world setting, the combination of SGLT-2i with metformin was associated with better adherence. The mean time until discontinuation was longer in the SGLT-2i group in comparison with the DPP-4i or SU groups.
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Affiliation(s)
- Bogdan Vlacho
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Clinical Trials Unit, Germans Trias i Pujol Health Science Research Institute (IGTP), Barcelona, Spain
- Pharmacology Department, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Spain
| | - Manel Mata-Cases
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Xavier Mundet-Tudurí
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Departament of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Joan-Antoni Vallès-Callol
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Jordi Real
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Magi Farre
- Pharmacology Department, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Spain
- Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Xavier Cos
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Primary and Hospital Innovation Department, Innovation Office at Institut Català de la Salut, Barcelona, Spain
| | - Kamlesh Khunti
- Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, United Kingdom
| | - Dídac Mauricio
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Endocrinology and Nutrition, Hospital Universitari de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Departament of Medicine, University of Vic - Central University of Catalonia, Vic, Spain
| | - Josep Franch-Nadal
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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García-Pérez LE, Boye KS, Rosilio M, Jung H, Heitmann E, Norrbacka K, Federici MO, Gentilella R, Guerci B, Giorgino F, Aigner U, Sapin H. The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES): Design and Baseline Characteristics. Diabetes Ther 2021; 12:1929-1946. [PMID: 34097244 PMCID: PMC8266969 DOI: 10.1007/s13300-021-01076-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 05/08/2021] [Indexed: 01/20/2023] Open
Abstract
INTRODUCTION The TROPHIES observational study enrolled patients with type 2 diabetes mellitus (T2DM) initiating their first injectable treatment with the glucagon-like peptide 1 receptor agonists (GLP-1 RAs) dulaglutide or liraglutide. This manuscript focuses on the study design, baseline characteristics of the enrolled population, and factors associated with GLP-1 RA choice. METHODS TROPHIES is a prospective, observational, 24-month study conducted in France, Germany, and Italy. Inclusion criteria include adult patients with T2DM, naïve to injectable antihyperglycemic treatments, initiating dulaglutide or liraglutide per routine clinical practice. The primary outcome is the duration of treatment on dulaglutide or liraglutide without a significant treatment change. RESULTS The analysis included 2181 patients (dulaglutide, 1130; liraglutide, 1051) (cutoff date May 15, 2019). The population was 56% male with mean [standard deviation (SD)] patient characteristics at baseline as follows: age, 59.2 (11.0) years; body mass index (BMI), 33.9 (6.6) kg/m2; T2DM duration, 8.5 (6.9) years; and glycated hemoglobin (HbA1c), 8.2 (1.3)%. Between-cohort demographic and clinical characteristics were balanced. The mean (SD) HbA1c and BMI values for French, German, and Italian patients were, respectively, 8.6 (1.4)%, 8.2 (1.4)%, 8.0 (0.8)%; 33.3 (6.1) kg/m2, 36.0 (7.2) kg/m2, and 32.6 (5.9) kg/m2. CONCLUSION This study analysis at baseline provides an opportunity to evaluate between-country differences in baseline HbA1c, weight, macrovascular complications, and factors driving GLP-1 RA selection for patients with T2DM in daily practice.
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Affiliation(s)
| | | | | | - Heike Jung
- Lilly Deutschland GmbH, Bad Homburg, Germany
| | | | | | | | | | - Bruno Guerci
- Hôpital Brabois Adultes, CHRU de Nancy and University of Lorraine, Nancy, France
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Mehta A, Niles AN, Vargas JH, Marafon T, Couto DD, Gross JJ. Acceptability and Effectiveness of Artificial Intelligence Therapy for Anxiety and Depression (Youper): Longitudinal Observational Study. J Med Internet Res 2021; 23:e26771. [PMID: 34155984 PMCID: PMC8423345 DOI: 10.2196/26771] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/04/2021] [Accepted: 04/03/2021] [Indexed: 01/04/2023] Open
Abstract
Background Youper is a widely used, commercially available mobile app that uses artificial intelligence therapy for the treatment of anxiety and depression. Objective Our study examined the acceptability and effectiveness of Youper. Further, we tested the cumulative regulation hypothesis, which posits that cumulative emotion regulation successes with repeated intervention engagement will predict longer-term anxiety and depression symptom reduction. Methods We examined data from paying Youper users (N=4517) who allowed their data to be used for research. To characterize the acceptability of Youper, we asked users to rate the app on a 5-star scale and measured retention statistics for users’ first 4 weeks of subscription. To examine effectiveness, we examined longitudinal measures of anxiety and depression symptoms. To test the cumulative regulation hypothesis, we used the proportion of successful emotion regulation attempts to predict symptom reduction. Results Youper users rated the app highly (mean 4.36 stars, SD 0.84), and 42.66% (1927/4517) of users were retained by week 4. Symptoms decreased in the first 2 weeks of app use (anxiety: d=0.57; depression: d=0.46). Anxiety improvements were maintained in the subsequent 2 weeks, but depression symptoms increased slightly with a very small effect size (d=0.05). A higher proportion of successful emotion regulation attempts significantly predicted greater anxiety and depression symptom reduction. Conclusions Youper is a low-cost, completely self-guided treatment that is accessible to users who may not otherwise access mental health care. Our findings demonstrate the acceptability and effectiveness of Youper as a treatment for anxiety and depression symptoms and support continued study of Youper in a randomized clinical trial.
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Affiliation(s)
- Ashish Mehta
- Department of Psychology, Stanford University, Stanford, CA, United States
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Lauffenburger JC, Barlev RA, Sears ES, Keller PA, McDonnell ME, Yom-Tov E, Fontanet CP, Hanken K, Haff N, Choudhry NK. Preferences for mHealth Technology and Text Messaging Communication in Patients With Type 2 Diabetes: Qualitative Interview Study. J Med Internet Res 2021; 23:e25958. [PMID: 34114964 PMCID: PMC8235286 DOI: 10.2196/25958] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 01/19/2021] [Accepted: 04/30/2021] [Indexed: 12/16/2022] Open
Abstract
Background Individuals with diabetes need regular support to help them manage their diabetes on their own, ideally delivered via mechanisms that they already use, such as their mobile phones. One reason for the modest effectiveness of prior technology-based interventions may be that the patient perspective has been insufficiently incorporated. Objective This study aims to understand patients’ preferences for mobile health (mHealth) technology and how that technology can be integrated into patients’ routines, especially with regard to medication use. Methods We conducted semistructured qualitative individual interviews with patients with type 2 diabetes from an urban health care system to elicit and explore their perspectives on diabetes medication–taking behaviors, daily patterns of using mobile technology, use of mHealth technology for diabetes care, acceptability of text messages to support medication adherence, and preferred framing of information within text messages to support diabetes care. The interviews were digitally recorded and transcribed. The data were analyzed using codes developed by the study team to generate themes, with representative quotations selected as illustrations. Results We conducted interviews with 20 participants, of whom 12 (60%) were female and 9 (45%) were White; in addition, the participants’ mean glycated hemoglobin A1c control was 7.8 (SD 1.1). Overall, 5 key themes were identified: patients try to incorporate cues into their routines to help them with consistent medication taking; many patients leverage some form of technology as a cue to support adherence to medication taking and diabetes self-management behaviors; patients value simplicity and integration of technology solutions used for diabetes care, managing medications, and communicating with health care providers; some patients express reluctance to rely on mobile technology for these diabetes care behaviors; and patients believe they prefer positively framed communication, but communication preferences are highly individualized. Conclusions The participants expressed some hesitation about using mobile technology in supporting diabetes self-management but have largely incorporated it or are open to incorporating it as a cue to make medication taking more automatic and less burdensome. When using technology to support diabetes self-management, participants exhibited individualized preferences, but overall, they preferred simple and positively framed communication. mHealth interventions may be improved by focusing on integrating them easily into daily routines and increasing the customization of content.
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Affiliation(s)
| | - Renee A Barlev
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Ellen S Sears
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | | | - Marie E McDonnell
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | | | | | - Kaitlin Hanken
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Nancy Haff
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Niteesh K Choudhry
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
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How representative is a point-of-care randomized trial? Clinical outcomes of patients excluded from a point-of-care randomized controlled trial evaluating antibiotic duration for Gram-negative bacteraemia: a multicentre prospective observational cohort study. Clin Microbiol Infect 2021; 28:297.e1-297.e6. [PMID: 34116204 DOI: 10.1016/j.cmi.2021.05.050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/26/2021] [Accepted: 05/31/2021] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Patients included in randomized controlled trials (RCT) are poorly representative of the general population. We compared outcomes of patients excluded from the PIRATE trial, a point-of-care RCT evaluating antibiotic durations for Gram-negative bacteraemia, with those of enrolled patients. METHODS A prospective observational cohort study, 'EPCO' (Excluded Patients' Clinical Outcomes) included patients excluded from the PIRATE trial. As in PIRATE, whose patients were randomized to 7-day, 14-day, or C-reactive-protein (CRP)-guided antibiotic durations, EPCO's primary outcome was occurrence of clinical success at 30 days. We also compared baseline characteristics, outcome rates and treatment-effect estimates. RESULTS In all, 405 patients were included in EPCO and compared with the 503 PIRATE patients. Reasons for exclusion were mainly medical (317/405; 78%), the most frequent being complicated infection. Excluded patients had more co-morbidities (Charlson median 3 versus 1, p < 0.001). Bacteraemia was more often health-care-associated (26% versus 9%, p < 0.001). The 30-day success rate was significantly lower among EPCO patients (299/396; 76% versus 469/493; 95%, p < 0.001), but the success rate was not significantly different for those excluded for non-medical reasons (68/75; 91%, p 0.09). There was no significant difference in failure rates of EPCO patients according to their treatment duration (difference 7 days versus 14 days: p 0.75; 7 days versus CRP-correspondent: p 1.00; 14 days versus CRP-correspondent: p 1.00). CONCLUSION Although point-of-care-randomized trials are more inclusive and representative than traditional RCTs, they are still likely to select patients with lower failure risk. Shorter antibiotic durations were not associated with failure in either included or excluded patients, supporting the generalizability of the PIRATE trial's findings.
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Showalter SL, Meneveau MO, Keim-Malpass J, Camacho TF, Squeo G, Anderson RT. Effects of Adjuvant Endocrine Therapy Adherence and Radiation on Recurrence and Survival Among Older Women with Early-Stage Breast Cancer. Ann Surg Oncol 2021; 28:7395-7403. [PMID: 33982163 DOI: 10.1245/s10434-021-10064-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 04/02/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND The Cancer and Leukemia Group-B 9343 (CALGB 9343) trial demonstrated that women aged ≥ 70 years with early-stage breast cancer can safely omit radiation therapy (RT) and be treated with breast-conserving surgery (BCS) and adjuvant endocrine therapy (AET) alone. AET adherence is low, leaving an undertreated cohort who may be at increased risk of recurrence and death. We hypothesized that AET adherence and adjuvant treatment choice impact recurrence and survival among CALGB 9343 eligible women. PATIENTS AND METHODS SEER-Medicare was used to identify CALGB 9343 eligible women who underwent BCS between 2007 and 2016. Medicare claims were used to identify AET use, and the proportion of days covered by AET was used to categorize adherent (PDC ≥ 0.80) versus nonadherent patients (PDC < 0.80). Recurrence-free, cancer-specific, and overall survival were assessed using Cox proportional hazards models. RESULTS In total, 10,719 women were identified, of whom 780 (7.3%) underwent BCS alone, 1490 (13.9%) underwent BCS + RT, 1663 (15.5%) underwent BCS + AET, and 6786 (63.3%) had BCS + RT + AET. Among women treated with BCS + AET, adherent patients had lower recurrence than did nonadherent patients (HR = 0.65, 95% CI: 0.50-0.85). With respect to adjuvant treatment combinations, there was no recurrence difference between the BCS + RT + AET group and BCS + AET group (HR = 0.81, 95% CI: 0.54-1.21). There was equivalent cancer-specific but worse overall survival in the BCS + AET group versus the BCS + AET + RT group. CONCLUSIONS While BCS + RT + AET may represent overtreatment for some, AET nonadherent women who omit RT are at risk for worse outcomes. Treatment decisions regarding RT omission should be tailored to the individual patient, taking into consideration the chances of AET nonadherence and the patients' own risk tolerance.
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Affiliation(s)
- Shayna L Showalter
- Department of Surgery, Division of Surgical Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA.
| | - Max O Meneveau
- Department of Surgery, Division of Surgical Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA
| | | | - T Fabian Camacho
- Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Gabriella Squeo
- Department of Surgery, Division of Surgical Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Roger T Anderson
- Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA
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Klotsman M, Adin CA, Anderson WH, Gilor C. Safety, Tolerability, and Proof-Of-Concept Study of OKV-119, a Novel Exenatide Long-Term Drug Delivery System, in Healthy Cats. Front Vet Sci 2021; 8:661546. [PMID: 34046446 PMCID: PMC8144329 DOI: 10.3389/fvets.2021.661546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 04/08/2021] [Indexed: 12/04/2022] Open
Abstract
Background: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in glucose homeostasis and food intake. In people, GLP-1 receptor agonists (GLP-1RAs) are commonly used for the treatment of type 2 diabetes mellitus (DM) and obesity; however, non-adherence to injectable medications is common. OKV-119 is an investigational drug delivery system intended for subdermal implantation and delivery of the GLP-1RA exenatide for up to 6 months. Hypothesis/Objectives: Develop protocols for the subcutaneous (SC) insertion and removal of OKV-119 and to evaluate its tolerability, in vivo drug-releasing characteristics, and weight-loss effects in cats. Animals: Two cadaveric and 19 purpose-bred cats. Methods: In cadavers, OKV-119 insertion protocol and imaging were performed at three SC locations. The safety and tolerability of OKV-119 implants were assessed in a small (n = 4 cats) 62-day study. Weekly plasma exenatide concentrations and body weight were measured in a 42-day proof-of-concept study designed to evaluate OKV-119 prototypes implanted in cats (n = 15). Results: In anesthetized cats, the duration of insertion and removal procedures was 1–2 min. OKV-119 was easily identified on radiographs, and well-tolerated without any apparent implant site reactions. Following implantation, exanatide plasma concentrations were observed for up to 35 days. Plasma exenatide concentrations were correlated to weight loss. Conclusion and clinical importance: Our findings suggest that OKV-119 could be easily inserted and removed during a routine clinic visit and can be used to safely and effectively deliver exenatide. Future studies of OKV-119, configured to release exenatide for a longer extended months-long duration, are warranted to determine whether the combination of metabolic improvements and beneficial weight-loss, coupled with minimal impact on pet-owner's lifestyle, lead to improved outcomes for obese cats and feline DM patients.
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Affiliation(s)
| | - Christopher A Adin
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States
| | - Wayne H Anderson
- Okava Pharmaceuticals, San Francisco, CA, United States.,Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Chen Gilor
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States
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Böhm AK, Schneider U, Aberle J, Stargardt T. Regimen simplification and medication adherence: Fixed-dose versus loose-dose combination therapy for type 2 diabetes. PLoS One 2021; 16:e0250993. [PMID: 33945556 PMCID: PMC8096115 DOI: 10.1371/journal.pone.0250993] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 04/16/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Suboptimal patient adherence to pharmacological therapy of type 2 diabetes may be due in part to pill burden. One way to reduce pill burden in patients who need multiple medications is to use fixed-dose combinations. Our study aimed to compare the effects of fixed-dose combination versus loose-dose combination therapy on medication adherence and persistence, health care utilization, therapeutic safety, morbidities, and treatment modification in patients with type 2 diabetes over three years. METHODS Using administrative data, we conducted a retrospective controlled cohort study comparing type 2 diabetes patients who switched from monotherapy to either a fixed-dose combination or a loose-dose combination. Adherence was assessed as the primary endpoint and calculated as the proportion of days covered with medication. After using entropy balancing to eliminate differences in observable baseline characteristics between the two groups, we applied difference-in-difference estimators for each outcome to account for time-invariant unobservable heterogeneity. RESULTS Of the 990 type 2 diabetes patients included in our analysis, 756 were taking a fixed-dose combination and 234 were taking a loose-dose combination. We observed a statistically significantly higher change in adherence (year one: 0.22, p<0.001, year two: 0.25, p<0.001, and year three: 0.29, p<0.001) as well as higher persistence and a smaller change in the number of drug prescriptions in each of the three years in the fixed-dose combination group compared to the loose-dose combination group. The differences were most pronounced in patients who were poorly adherent, had a high pill burden, or did not have a severe concomitant disease. CONCLUSION Our results indicate that taking a fixed-dose combination can lead to a significant improvement in adherence to pharmacological therapy of type 2 diabetes compared to a loose-dose combination. In particular, these findings suggest that reducing pill burden may improve disease management among patients with more complex medication demand and patients who have demonstrated poor medication adherence.
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Affiliation(s)
- Anna-Katharina Böhm
- Hamburg Center for Health Economics, University of Hamburg, Hamburg, Germany
| | | | - Jens Aberle
- Department Endocrinology and Diabetology, University Obesity Center Hamburg, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Tom Stargardt
- Hamburg Center for Health Economics, University of Hamburg, Hamburg, Germany
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