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Katsimardou A, Theofilis P, Vordoni A, Doumas M, Kalaitzidis RG. The Effects of SGLT2 Inhibitors on Blood Pressure and Other Cardiometabolic Risk Factors. Int J Mol Sci 2024; 25:12384. [PMID: 39596449 PMCID: PMC11594301 DOI: 10.3390/ijms252212384] [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: 10/12/2024] [Revised: 11/12/2024] [Accepted: 11/15/2024] [Indexed: 11/28/2024] Open
Abstract
Beyond their established hypoglycemic, cardioprotective, and nephroprotective properties, sodium-glucose cotransporters 2 (SGLT2) inhibitors exert other pleiotropic actions on blood pressure levels, body weight, and lipid metabolism. Blood pressure (BP) reduction varies based on the background history, including an effect on systolic, diastolic BP, and 24 h BP measurements. The reduction in body weight between 1 and 2 kg for the first months is caused by a reduction in visceral and subcutaneous fat due to glycosuria and loss of calories. Regarding lipid metabolism, a reduction in triglycerides and an increase in total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) have been reported, although these alterations are small and could provide additional cardiovascular protection. Various pathophysiologic mechanisms have been proposed to explain the above-mentioned pleiotropic actions of SGLT2 inhibitors. Natriuresis, osmotic diuresis, body weight reduction, amelioration of endothelial dysfunction and arterial stiffness, sympathetic tone decrease, and uric acid reduction are among those that have been suggested for BP reduction. Apart from glycosuria and calorie loss, other mechanisms seem to contribute to body weight reduction, such as the beiging of white adipose tissue, while the mechanisms involved in lipid metabolism alterations have not been clearly determined.
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Affiliation(s)
- Alexandra Katsimardou
- 2nd Department of Internal Medicine, 401 General Military Hospital of Athens, 11525 Athens, Greece; (A.K.); (M.D.)
- 2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, General Hospital “Hippokration”, 54642 Thessaloniki, Greece
| | - Panagiotis Theofilis
- Center for Nephrology “G. Papadakis”, General Hospital of Nikaia-Piraeus “Ag. Panteleimon”, 18454 Nikaia, Greece; (P.T.); (A.V.)
| | - Aikaterini Vordoni
- Center for Nephrology “G. Papadakis”, General Hospital of Nikaia-Piraeus “Ag. Panteleimon”, 18454 Nikaia, Greece; (P.T.); (A.V.)
| | - Michael Doumas
- 2nd Department of Internal Medicine, 401 General Military Hospital of Athens, 11525 Athens, Greece; (A.K.); (M.D.)
| | - Rigas G. Kalaitzidis
- Center for Nephrology “G. Papadakis”, General Hospital of Nikaia-Piraeus “Ag. Panteleimon”, 18454 Nikaia, Greece; (P.T.); (A.V.)
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Wang Y, Jiang C, Dong X, Chen M, Gu Q, Zhang L, Fu Y, Pan T, Bi Y, Song W, Xu J, Lu W, Sun X, Ye Z, Zhang D, Peng L, Lin X, Dai W, Wang Q, Yang W. Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial. Diabetes Obes Metab 2024; 26:2774-2786. [PMID: 38618970 DOI: 10.1111/dom.15596] [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: 12/25/2023] [Revised: 03/25/2024] [Accepted: 03/25/2024] [Indexed: 04/16/2024]
Abstract
AIM This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
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Affiliation(s)
- Yao Wang
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China
| | - Chengxia Jiang
- Department of Endocrinology, Yibin Second People's Hospital, Yibin, China
| | - Xiaolin Dong
- Department of Endocrinology, Jinan Central Hospital, Jinan, China
| | - Mingwei Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qin Gu
- Department of Endocrinology, Huadong Hospital affiliated to Fudan University, Shanghai, China
| | - Lihui Zhang
- Department of Endocrinology, Hebei Medical University Second Hospital, Shijiazhuang, China
| | - Yanqin Fu
- Department of Endocrinology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tianrong Pan
- Department of Endocrinology, The Second Hospital of Anhui Medical University, Hefei, China
| | - Yan Bi
- Department of Endocrinology, Nanjing Drum Tower Hospital, Nanjing, China
| | - Weihong Song
- Department of Endocrinology, Chenzhou First People's Hospital, Chenzhou, China
| | - Jing Xu
- Department of Endocrinology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - WeiPing Lu
- Department of Endocrinology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Xiaodong Sun
- Department of Endocrinology, Weifang Medical College Affiliated Hospital, Weifang, China
| | - Zi Ye
- Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
| | - Danli Zhang
- Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
| | - Liang Peng
- Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
| | - Xiang Lin
- Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
| | - Wei Dai
- Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
| | - Quanren Wang
- Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
| | - Wenying Yang
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China
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Longo M, Caruso P, Scappaticcio L, Maiorino MI, Bellastella G, Capuano A, Esposito K, Giugliano D. Two years with GIOIA 'Effects of gliflozins and gliptins on markers of cardiovascular damage in type 2 diabetes': A prospective, multicentre, quasi-experimental study on sodium-glucose cotransporter 2 and dipeptidyl peptidase-4 inhibitors in diabetes clinical practice. Diabetes Obes Metab 2024; 26:1492-1501. [PMID: 38234208 DOI: 10.1111/dom.15451] [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: 11/06/2023] [Revised: 12/13/2023] [Accepted: 12/21/2023] [Indexed: 01/19/2024]
Abstract
AIM To assess and compare the metabolic and vascular effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in the clinical practice of patients with type 2 diabetes in Italy. MATERIALS AND METHODS GIOIA is a 2-year prospective, multicentre, quasi-experimental study that enrolled patients with type 2 diabetes initiating SGLT-2i or DPP-4i for inadequate glycaemic control [glycated haemoglobin (HbA1c) >7%] between March 2018 and March 2021. The primary endpoints were changes in markers of organ damage [carotid intima-media thickness (CIMT), albuminuria, myocardial function] and HbA1c from baseline to year 2. RESULTS In total, 1150 patients were enrolled in the study (SGLT-2i n = 580, DPP-4i n = 570). Patients initiated on SGLT-2i were younger (about 6 years) and heavier (about 11 kg), had higher HbA1c level (1% more), more albuminuria and cardiovascular events (16% more) than patients initiated on DPP-4i. CIMT and echocardiographic parameters were not significantly different. Propensity score matching yielded two groups, each consisting of 155 patients with diabetes with similar baseline characteristics. Despite a significant similar reduction in HbA1c levels in both groups (-0.8%), more patients on SGLT-2i had regression of CIMT and albuminuria (22% and 10%, respectively, p < .001 vs. DPP-4i); more patients on DPP-4i had progression of CIMT and albuminuria (23% and 28%, respectively, p < .001 vs. SGLT-2i). Left ventricular ejection fraction improved slightly (3%, p = .043) on SGLT-2i only. CONCLUSIONS In a real-world setting, both SGLT-2i and DPP-4i improve glycaemic control persisting after 2 years of treatment, with a robust effect on both CIMT and albuminuria regression for SGLT-2i as compared with DPP-4i in the propensity score matching.
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Affiliation(s)
- Miriam Longo
- Department of Advanced Medical and Surgical Sciences, Division of Endocrinology and Diabetes, University of Campania 'Luigi Vanvitelli', Naples, Italy
| | - Paola Caruso
- Department of Advanced Medical and Surgical Sciences, Division of Endocrinology and Diabetes, University of Campania 'Luigi Vanvitelli', Naples, Italy
| | - Lorenzo Scappaticcio
- Department of Advanced Medical and Surgical Sciences, Division of Endocrinology and Diabetes, University of Campania 'Luigi Vanvitelli', Naples, Italy
| | - Maria Ida Maiorino
- Department of Advanced Medical and Surgical Sciences, Division of Endocrinology and Diabetes, University of Campania 'Luigi Vanvitelli', Naples, Italy
| | - Giuseppe Bellastella
- Department of Advanced Medical and Surgical Sciences, Division of Endocrinology and Diabetes, University of Campania 'Luigi Vanvitelli', Naples, Italy
| | - Annalisa Capuano
- Section of Pharmacology 'L. Donatelli', Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Katherine Esposito
- Department of Advanced Medical and Surgical Sciences, Division of Endocrinology and Diabetes, University of Campania 'Luigi Vanvitelli', Naples, Italy
| | - Dario Giugliano
- Department of Advanced Medical and Surgical Sciences, Division of Endocrinology and Diabetes, University of Campania 'Luigi Vanvitelli', Naples, Italy
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Huang ST, Bair PJ, Chang SS, Kao YN, Chen SN, Wang IK, Chiu CW, Chang CT, Shih YH, Li CY, Yu TM. Risk of Diabetic Retinopathy in Patients With Type 2 Diabetes After SGLT-2 Inhibitors: A Nationwide Population Cohort Study. Clin Pharmacol Ther 2024; 115:95-103. [PMID: 37804230 DOI: 10.1002/cpt.3074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 09/19/2023] [Indexed: 10/09/2023]
Abstract
Diabetic retinopathy (DR) accounts for 80% of cases of vision loss in patients with type 2 diabetes mellitus (T2DM). Interventional treatments are only indicated in advanced DR and are ineffective in some patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are used to attenuate T2DM-associated cardiovascular complications. We conducted the cohort study to investigate the effect of SGLT2is on DR development. Data (May 2016-December 2018) obtained from the Taiwan National Health Insurance Research Database were analyzed in this nationwide retrospective cohort study. After propensity score matching, a total of 31,764 patients receiving SGLT2is and another 31,764 patients receiving dipeptidyl peptidase 4 inhibitors (DPP4is) were included in this study. Multiple Cox proportional-hazards regression models were used to evaluate DR risk. Overall DR incidence among SGLT2i or DPP4i users was 10.9 or 15.6 per 10,000 patient-years, respectively. After covariate adjustment, DR (both early and late stage) risk was substantially lower in SGLT2i users (adjusted hazard ratio: 0.68, 95% confidence interval: 0.6-0.78) than in DPP4i users. DR risk appears to be considerably lower in SGLT2i users than in DPP4i users. Glycemic control measurement with HbA1C level was unavailable in this claim database.
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Affiliation(s)
- Shih-Ting Huang
- Division of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Pei-Jane Bair
- School of Medicine, China Medical University, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung, Taiwan
| | - Shih-Sheng Chang
- School of Medicine, China Medical University, Taichung, Taiwan
- Division of Cardiovascular Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yu-Nong Kao
- Division of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - San-Ni Chen
- Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan
| | - I-Kang Wang
- School of Medicine, China Medical University, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung, Taiwan
| | - Chih-Wei Chiu
- Division of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chi-Tzung Chang
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Ying-Hsiu Shih
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Chi-Yuan Li
- Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung, Taiwan
| | - Tung-Min Yu
- Division of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung, Taiwan
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Rastogi A, Januzzi JL. Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors in Cardiovascular Disease and Chronic Kidney Disease. J Clin Med 2023; 12:2824. [PMID: 37109162 PMCID: PMC10143176 DOI: 10.3390/jcm12082824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 03/20/2023] [Accepted: 04/03/2023] [Indexed: 04/29/2023] Open
Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular and renal outcomes in patients with established cardiovascular disease, chronic kidney disease (CKD), and heart failure (HF) with reduced or preserved ejection fraction. Clinical benefit has been substantiated in patients with and without type 2 diabetes (T2D). Consequently, SGLT2is have an increasingly important role in HF and CKD management that extends beyond T2D treatment. Their pleiotropic pharmacological effects underlying their cardiovascular and renal benefits are not completely understood but include significant effects beyond blood glucose reduction. SGLT2is inhibit the reabsorption of glucose and sodium in the proximal tubule which, in addition to lowering blood glucose, activates tubuloglomerular feedback, leading to reduced glomerular hydrostatic pressure and the mitigation of glomerular filtration rate loss. SGLT2is have diuretic and natriuretic effects, leading to decreased blood pressure, preload, and left ventricular (LV) filling pressure, and improvements in other surrogates of afterload. In HF, SGLT2is mitigate the risks of hyperkalemia and ventricular arrhythmia and improve LV dysfunction. SGLT2is also reduce sympathetic tone and uric acid levels, increase hemoglobin levels, and are postulated to have anti-inflammatory properties. This narrative review discusses the multifactorial and interrelated pharmacological mechanisms underlying the cardiovascular and renal benefits of SGLT2is.
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Affiliation(s)
- Anjay Rastogi
- David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
| | - James L. Januzzi
- Massachusetts General Hospital, Boston, MA 02114, USA;
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
- Baim Institute for Clinical Research, Boston, MA 02215, USA
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Estimation of marginal structural models under irregular visits and unmeasured confounder: calibrated inverse probability weights. BMC Med Res Methodol 2023; 23:4. [PMID: 36611135 PMCID: PMC9825036 DOI: 10.1186/s12874-022-01831-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 12/26/2022] [Indexed: 01/09/2023] Open
Abstract
Clinical information collected in electronic health records (EHRs) is becoming an essential source to emulate randomized experiments. Since patients do not interact with the healthcare system at random, the longitudinal information in large observational databases must account for irregular visits. Moreover, we need to also account for subject-specific unmeasured confounders which may act as a common cause for treatment assignment mechanism (e.g. glucose-lowering medications) while also influencing the outcome (e.g. Hemoglobin A1c). We used the calibration of longitudinal weights to improve the finite sample properties and to account for subject-specific unmeasured confounders. A Monte Carlo simulation study is conducted to evaluate the performance of calibrated inverse probability estimators using time-dependent treatment assignment and irregular visits with subject-specific unmeasured confounders. The simulation study showed that the longitudinal weights with calibrated restrictions improved the finite sample bias when compared to the stabilized weights. The application of the calibrated weights is demonstrated using the exposure of glucose lowering medications and the longitudinal outcome of Hemoglobin A1c. Our results support the effectiveness of glucose lowering medications in reducing Hemoglobin A1c among type II diabetes patients with elevated glycemic index ([Formula: see text]) using stabilized and calibrated weights.
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Wilson E, Jones A, Brandt NJ. Sodium-Glucose Cotransporter-2 Inhibitors: Risks vs. Rewards When Caring for Older Adults. J Gerontol Nurs 2022; 48:7-13. [PMID: 36169298 DOI: 10.3928/00989134-20220908-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Managing multiple comorbidities is common in older adults. Thus, when a medication class, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, can potentially treat multiple conditions and prevent progression of chronic kidney disease, multiple guidelines must be followed when using these agents. The current article discusses risks and benefits of SGLT2 inhibitors, especially in the context of new evidence, and presents a case example. [Journal of Gerontological Nursing, 48(10), 7-13.].
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Hejjaji V, Gorgojo-Martinez JJ, Tang F, Garnelo JB, Cooper A, Medina J, Mutiozabal MS, Khunti K, Nicolucci A, Shestakova MV, Ji L, Gomes MB, Watada H, Vora J, Malik AO, Kosiborod M, Arnold SV. Factors associated with weight loss in people with overweight or obesity living with type 2 diabetes mellitus: Insights from the global DISCOVER study. Diabetes Obes Metab 2022; 24:1734-1740. [PMID: 35546275 DOI: 10.1111/dom.14745] [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: 10/26/2021] [Revised: 04/12/2022] [Accepted: 04/26/2022] [Indexed: 11/27/2022]
Abstract
AIMS To estimate real-world change in weight over 3 years and the factors influencing it in participants who are overweight and live with type 2 diabetes. MATERIALS AND METHODS DISCOVER is a multinational prospective observational study that enrolled participants with type 2 diabetes between December 2014 and June 2016 at the time of initiation of a second-line glucose-lowering medication (GLM). Demographic, anthropometric, and quality-of-life data were collected at baseline, and after 6, 12, 24 and 36 months of follow-up. Using a hierarchical, repeated-measures linear regression model, we examined factors associated with weight change over time. RESULTS Of 10 675 participants with type 2 diabetes who were overweight/obese (mean age 57.1 ± 11.1 years, 46% women), 21% lost ≥5% weight over 3 years, which was associated with modestly improved physical and mental health. Advancing age, female sex, and higher baseline weight were associated with weight loss. Most importantly, the type of GLM prescribed at previous visit had the strongest impact on weight change over time independent of participant factors, with use of a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist associated with 1.0% weight loss versus a 0.6% weight gain with sulphonylureas, thiazolidinediones, meglitinides or insulin. CONCLUSION In this large contemporary prospective study, approximately one in five participants with early-stage type 2 diabetes and overweight/obesity lost ≥5% weight over 3 years. The type of GLM has the most impact on weight loss over time, highlighting the need for a careful selection of agents that takes baseline weight into consideration.
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Affiliation(s)
- Vittal Hejjaji
- Saint Luke's Mid America Heart Institute/University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Juan J Gorgojo-Martinez
- Unit of Endocrinology and Nutrition, Hospital Universitario Fundación Alcorcón Madrid, Madrid, Spain
| | - Fengming Tang
- Saint Luke's Mid America Heart Institute/University of Missouri-Kansas City, Kansas City, Missouri, USA
| | | | | | | | | | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Antonio Nicolucci
- Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy
| | - Marina V Shestakova
- Endocrinology Research Center, Diabetes Institute, Moscow, Russian Federation
| | - Linong Ji
- Peking University Subjects's Hospital, Beijing, China
| | | | - Hirotaka Watada
- Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | | | - Ali O Malik
- Saint Luke's Mid America Heart Institute/University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Mikhail Kosiborod
- Saint Luke's Mid America Heart Institute/University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Suzanne V Arnold
- Saint Luke's Mid America Heart Institute/University of Missouri-Kansas City, Kansas City, Missouri, USA
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Alqudah A, Oqal M, Al-Samdi A, Qnais E, Wedyan M, Abu Gneam M, Alnajjar R, Alajarmeh M, Yousef E, Gammoh O. Knowledge and practice of community pharmacists towards SGLT2 inhibitors. F1000Res 2022; 11:659. [PMID: 35811806 PMCID: PMC9237554 DOI: 10.12688/f1000research.122170.1] [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] [Accepted: 05/24/2022] [Indexed: 09/05/2024] Open
Abstract
Background: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs which improve glycaemic control in type 2 diabetes mellitus (T2DM) by preventing the kidney from reabsorbing glucose back to blood. Community pharmacists have long-term relationships with most of their chronic patients, so they play a key role in care for people with diabetes. Therefore, the objective of this study was to assess pharmacists' knowledge and practice towards SGLT2 inhibitors. Methods: A cross-sectional study was conducted to meet the study objectives. A convenience sample of 348 community pharmacists in Jordan was recruited. knowledge and practice were assessed using a self-administered questionnaire created for the purpose of this study. Results: A total of 400 community pharmacists were reached, of whom 348 answered the survey (response rate 87%). The results indicated that SGLT2 inhibitors knowledge score among community pharmacists in Jordan was 6.61 (out of 12). Factors like age, gender, location of the pharmacy, years of pharmacists' experience had no effect on knowledge score; however, pharmacists who attended training courses on diabetes had higher knowledge scores. Additionally, pharmacists' dispensing practice toward SGLT2 inhibitors had insufficient knowledge, such as lack of knowledge about the superiority of SGLT2 inhibitors over other anti-diabetics and inability to give the best advice to patients. Conclusions: Our findings reflect a moderate knowledge among community pharmacists about SGLT2 inhibitors which may negatively affect the patients' outcome; thus, continuous education for the pharmacists is essential.
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Affiliation(s)
- Abdelrahim Alqudah
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Muna Oqal
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, 13133, Jordan
| | - Ahmad Al-Samdi
- Department of Adult Health Nursing, Princess Salma Faculty of Nursing, Al al-Bayt University, Al-Mafraq, Zarqa, 13133, Jordan
| | - Esam Qnais
- Department of Biology and Biotechnology, Faculty of Science, Hashemite University, Zarqa, Zarqa, 13133, Jordan
| | - Mohammed Wedyan
- Department of Biology and Biotechnology, Faculty of Science, Hashemite University, Zarqa, Zarqa, 13133, Jordan
| | - Majd Abu Gneam
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Roaa Alnajjar
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Manar Alajarmeh
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Elaf Yousef
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Omar Gammoh
- Department of Clinical Pharmacy and Pharmacy Practice, Yarmouk University, Irbid, Zarqa, 13133, Jordan
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Alqudah A, Oqal M, Al-Samdi A, Qnais E, Wedyan M, Abu Gneam M, Alnajjar R, Alajarmeh M, Yousef E, Gammoh O. Knowledge and practice of community pharmacists towards SGLT2 inhibitors. F1000Res 2022; 11:659. [PMID: 35811806 PMCID: PMC9237554 DOI: 10.12688/f1000research.122170.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/28/2022] [Indexed: 11/20/2022] Open
Abstract
Background: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs which improve glycaemic control in type 2 diabetes mellitus (T2DM) by preventing the kidney from reabsorbing glucose back to blood. Community pharmacists have long-term relationships with most of their chronic patients, so they play a key role in care for people with diabetes. Therefore, the objective of this study was to assess pharmacists' knowledge and practice towards SGLT2 inhibitors. Thus, improving pharmacists' knowledge about this group of medications could improve the treatment outcome of people with diabetes. Methods: A cross-sectional study was conducted to meet the study objectives. A convenience sample of 348 community pharmacists in Jordan was recruited. knowledge and practice were assessed using a self-administered questionnaire created for the purpose of this study. Results: A total of 400 community pharmacists were reached, of whom 348 answered the survey (response rate 87%). The results indicated that SGLT2 inhibitors knowledge score among community pharmacists in Jordan was 6.61 (out of 12). Factors like age, gender, location of the pharmacy, years of pharmacists' experience had no effect on knowledge score; however, pharmacists who attended training courses on diabetes had higher knowledge scores. Additionally, pharmacists' dispensing practice toward SGLT2 inhibitors had insufficient knowledge, such as lack of knowledge about the superiority of SGLT2 inhibitors over other anti-diabetics and inability to give the best advice to patients. Conclusions: Our findings reflect a moderate knowledge among community pharmacists about SGLT2 inhibitors which may negatively affect the patients' outcome; thus, continuous education for the pharmacists is essential.
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Affiliation(s)
- Abdelrahim Alqudah
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Muna Oqal
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, 13133, Jordan
| | - Ahmad Al-Samdi
- Department of Adult Health Nursing, Princess Salma Faculty of Nursing, Al al-Bayt University, Al-Mafraq, Zarqa, 13133, Jordan
| | - Esam Qnais
- Department of Biology and Biotechnology, Faculty of Science, Hashemite University, Zarqa, Zarqa, 13133, Jordan
| | - Mohammed Wedyan
- Department of Biology and Biotechnology, Faculty of Science, Hashemite University, Zarqa, Zarqa, 13133, Jordan
| | - Majd Abu Gneam
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Roaa Alnajjar
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Manar Alajarmeh
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Elaf Yousef
- Department of clinical pharmacy and pharmacy practice, Faculty of pharmaceutical sciences, The Hashemite University, Zarqa, Zarqa, P.O box 330127, Zarqa 13133, Jordan, Jordan
| | - Omar Gammoh
- Department of Clinical Pharmacy and Pharmacy Practice, Yarmouk University, Irbid, Zarqa, 13133, Jordan
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11
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Singh AK, Singh R. Relook at DPP-4 inhibitors in the era of SGLT-2 inhibitors. World J Diabetes 2022; 13:466-470. [PMID: 35800411 PMCID: PMC9210541 DOI: 10.4239/wjd.v13.i6.466] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/19/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
SGLT-2 inhibitors (SGLT-2Is) have significantly improved cardio-renal outcomes and are preferred agents in people with cardiovascular diseases, heart failure, and diabetic kidney disease. Similarly, GLP-1 receptor agonists (GLP-1RAs) have significantly improved atherosclerotic cardiovascular outcomes. To this end, DPP-4 inhibitors (DPP-4Is) are cardiac-neutral drugs. While long-acting GLP-1RAs have shown a favorable HbA1c lowering compared to DPP-4Is, there is no clinically meaningful HbA1c lowering difference between SGLT-2Is vs DPP-4Is. Moreover, the glucose-lowering potential of SGLT-2Is gets compromised with a progressive decline in renal functions, unlike DPP-4Is. Furthermore, the HbA1c lowering potential of DPP-4Is is favorable in people with T2DM having a modest baseline HbA1c (8.0%-8.5%) compared with SGLT-2Is which lowers HbA1c larger in a background of higher baseline HbA1c (> 8.5%-9.0%). These findings suggest that the role of DPP-4Is in the management of type 2 diabetes mellitus cannot be completely ignored even in the era of SGLT-2Is.
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Affiliation(s)
- Awadhesh Kumar Singh
- Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, Kolkata 700013, West Bengal, India
| | - Ritu Singh
- Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, Kolkata 700013, West Bengal, India
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12
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Real-world evaluation of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors for managing type 2 diabetes mellitus: a retrospective multi-ethnic cohort study. J Diabetes Metab Disord 2022; 21:521-555. [PMID: 35673518 PMCID: PMC9167339 DOI: 10.1007/s40200-022-01004-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 02/07/2022] [Indexed: 11/29/2022]
Abstract
Abstract Purpose Sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors are increasingly used as second-line therapies in patients with type 2 diabetes. The aim of this study was to assess the real-world effects of SGLT2 inhibitors in a multi-ethnic population in Singapore. Methods This retrospective cohort study examined patients diagnosed with and treated for diabetes from the Ministry of Health’s administrative database. Differences in outcomes between treatment groups were assessed using Poisson regression. Demographics, clinical characteristics, previous diagnoses and hospitalisations, and diabetes medication history were used for propensity score matching. Subgroup analyses by ethnicity were performed. Effect size was estimated using risk ratios (RRs) with 95% confidence intervals (CIs). Results Patients initiating SGLT2 inhibitors were more likely to achieve glycaemic control target than DPP4 inhibitor-treated patients (RR 1.09; 95% CI 1.04, 1.14). This was observed only in patients of Chinese ethnicity. A higher risk of diabetic ketoacidosis in SGLT2 inhibitor initiators was not observed. SGLT2 inhibitors were associated with reduced risk of hypoglycaemia (RR 0.69; 95% CI 0.59, 0.82) and urinary tract infection (RR 0.52; 95% CI 0.43, 0.63) but was not statistically significant for hypoglycaemia in Malay patients. Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with 12% and 34% reduction in any-cause hospitalisation and all-cause mortality, respectively, potentially resulting in more than $50 million savings over 10 years. Conclusion SGLT2 inhibitors were associated with improvements in glycaemic control, reduced risk of complications, and was well tolerated. Ethnicity also plays a role and should be considered in future studies.
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Oh S, Purja S, Shin H, Kim M, Kim E. Hypoglycemic agents and glycemic variability in individuals with type 2 diabetes: A systematic review and network meta-analysis. Diab Vasc Dis Res 2022; 19:14791641221106866. [PMID: 35686694 PMCID: PMC9189550 DOI: 10.1177/14791641221106866] [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] [Indexed: 11/23/2022] Open
Abstract
While hemoglobin A1c (HbA1c) is commonly used to monitor therapy response in type 2 diabetes (T2D), GV is emerging as an essential additional metric for optimizing glycemic control. Our goal was to learn more about the impact of hypoglycemic agents on HbA1c levels and GV in patients with T2D. A systematic review and network meta-analysis (NMA) of randomized controlled trials were performed to assess the effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter (SGLT)-2 inhibitors, dipeptidyl peptidase (DPP)-4 inhibitors, sulfonylurea and thiazolidinediones on Mean Amplitude of Glycemic Excursions (MAGE) and HbA1c. Searches were performed using PubMed and EMBASE. A random-effect model was used in the NMA, and the surface under the cumulative ranking was used to rank comparisons. All studies were checked for quality according to their design and also for heterogeneity before inclusion in this NMA. The highest reduction in MAGE was achieved by GLP-1 RAs (SUCRA 0.83), followed by DPP-4 inhibitors (SUCRA: 0.72), and thiazolidinediones (SUCRA: 0.69). In terms of HbA1c reduction, GLP-1 RAs were the most effective (SUCRA 0.81), followed by DPP-4 inhibitors (SUCRA 0.72) and sulfonylurea (SUCRA 0.65). Our findings indicated that GLP-1 RAs have relatively high efficacy in terms of HbA1c and MAGE reduction when compared with other hypoglycemic agents and can thus have clinical application. Future studies with a larger sample size and appropriate subgroup analyses are warranted to completely understand the glycemic effects of these agents in various patients with T2D. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42021256363).
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Affiliation(s)
- SuA Oh
- Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
| | - Sujata Purja
- Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
- EunYoung Kim, Data science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
| | - Hocheol Shin
- Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
| | - Minji Kim
- Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
| | - Eunyoung Kim
- Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
- EunYoung Kim, Data science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
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Costa Gil JE, Garnica Cuéllar JC, Perez Terns P, Ferreira-Hermosillo A, Cetina Canto JA, Garduño Perez ÁA, Mendoza Martínez P, Rista L, Sosa-Caballero A, Vázquez-Mendez E, Tejado Gallegos LF, Chen H, Elizalde A, Tomatis VB. Patients' Preference Between DPP4i and SGLT2i for Type 2 Diabetes Treatment: A Cross-Sectional Evaluation. Patient Prefer Adherence 2022; 16:1201-1211. [PMID: 35592774 PMCID: PMC9112794 DOI: 10.2147/ppa.s355638] [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: 01/19/2022] [Accepted: 04/06/2022] [Indexed: 12/02/2022] Open
Abstract
PURPOSE Despite newer type 2 diabetes (T2D) medications, patients do not always achieve metabolic targets, remaining at risk for cardiorenal complications. Therapeutic decisions are generally made by the healthcare team without considering patients' preferences. We aimed to evaluate patients' T2D treatment preference in two Latin-American countries between two different oral medication profiles, one resembling dipeptidyl peptidase-4 inhibitors (DPP4i) and another resembling sodium-glucose cotransporter-2 inhibitors (SGLT2i). PATIENTS AND METHODS In this cross-sectional, multicenter study from June to September 2020, patients with T2D from Argentina and Mexico (n = 390) completed a discrete choice experiment questionnaire to identify preferences between DPP4i (medication profile A) and SGLT2i (medication profile B). The reason behind patients' choice, and the association between their baseline characteristics and their preference were evaluated using logistic regression methods. RESULTS Most participants (88.2%) preferred SGLT2i's profile. Participants with older age (p = 0.0346), overweight or obesity (p < 0.0001), high blood pressure (BP; p < 0.0001), high total cholesterol (p = 0.0360), and glycosylated hemoglobin (HbA1c) <7% (p = 0.0001) were more likely to choose SGLT2i compared with DPP4i's profile. The most and least important reasons to choose either drug profile were HbA1c reduction and genital infection risk, respectively. The likelihood of selecting the SGLT2i's profile significantly increased in participants with increased body mass index (BMI; odds ratio [OR] = 8.9, 95% confidence interval [CI]: 3.5-22.5, p < 0.05), high BP (OR = 4.9, 95% CI: 1.9-12.4, p < 0.05), and lower education level (OR = 3.6, 95% CI: 1.0-12.6, p < 0.05). CONCLUSION Latin-American patients with T2D preferred medication with a profile resembling SGLT2i over one resembling DPP4i as a treatment option. A patient-centered approach may aid the healthcare team in decision-making for improved outcomes.
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Affiliation(s)
- José Esteban Costa Gil
- Departamento de Endocrinología, Instituto de Cardiología La Plata, La Plata, Buenos Aires, Argentina
- Correspondence: José Esteban Costa Gil, Costa Gil Departamento de Endocrinología, Instituto de Cardiología La Plata, Calle 6, número 212, La Plata, 1900, Buenos Aires, Argentina, Tel +54 9 2214 20-7359, Email
| | - Juan Carlos Garnica Cuéllar
- Departamento de Endocrinología del Centro Médico Nacional “20 de Noviembre”, ISSSTE, Ciudad de México, México
| | - Paula Perez Terns
- Dirección Médica, Cardiología Palermo - Centro de Investigaciones Clínicas, Buenos Aires, Argentina
| | - Aldo Ferreira-Hermosillo
- Unidad de Investigación Médica en Enfermedades Endócrinas. Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | | | - Ángel Alfonso Garduño Perez
- Departamento de Endocrinología del Centro Médico Nacional “20 de Noviembre”, ISSSTE, Ciudad de México, México
| | | | - Lucas Rista
- Diabetes, Innovación e Investigación, Centro de Diabetes y Nutrición - Investigaciones Clínicas (CEDyN), Rosario, Santa Fé, Argentina
| | | | | | | | - Hungta Chen
- Global Medical & Payer Evidence Statistics, AstraZeneca, Gaithersburg, Maryland, USA
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15
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Scheen AJ. Efficacy / safety balance of DPP-4 inhibitors versus SGLT2 inhibitors in elderly patients with type 2 diabetes. DIABETES & METABOLISM 2021; 47:101275. [PMID: 34481962 DOI: 10.1016/j.diabet.2021.101275] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 08/07/2021] [Indexed: 12/14/2022]
Abstract
Dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) offer new options for the oral management of type 2 diabetes mellitus (T2DM), with the advantage in the elderly population to be devoid of a high risk of hypoglycaemia. SGLT2is have also shown benefits regarding cardiovascular (heart failure) and renal protection, including in patients with T2DM aged ≥ 65 years while DPP-4is have only proved cardiovascular and renal safety without superiority compared with placebo. The glucose-lowering efficacy of the two pharmacological classes is almost similar including in older patients with T2DM. However, the tolerance and safety profile may be highly different and overall more favourable with DPP-4is than with SGLT2is. Some adverse events have been reported with SGLT2is which may be more prevalent or severe in older patients than in younger patients. The present comprehensive review focuses on the benefit/risk balance in the elderly population with T2DM by comparing the profile of DPP-4is and SGLT2is regarding the following potential issues: metabolic disorders (hypoglycaemia and diabetic ketoacidosis); cardiac and vascular issues (atheromatous cardiovascular disease, heart failure, volume reduction hypotension, and lower limb amputations); renal endpoints including acute renal injury; risk of infections; digestive disorders; bone and skin adverse events; and cancer risk. Both DPP-4is and SGLT2is have their own advantages and disadvantages. Personalised treatment is recommended based upon the efficacy/safety profile of each drug class and individual patient characteristics that may be markedly different among the heterogeneous population of older individuals with T2DM.
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Affiliation(s)
- André J Scheen
- Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium; Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium.
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Obaya Rebollar JC, Miravet Jiménez S, Aranbarri Osoro I, Carramiñana Barrera FC, García Soidán FJ, Cebrián Cuenca AM. [Management of patient profiles with type2 diabetes mellitus in Primary Care in Spain: CONTROVERTI2 Program]. Semergen 2021; 48:23-37. [PMID: 34452834 DOI: 10.1016/j.semerg.2021.07.009] [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: 04/27/2021] [Revised: 07/16/2021] [Accepted: 07/26/2021] [Indexed: 01/14/2023]
Abstract
AIM To identify existing controversies in the routine management of patients with T2D and to contrast them with the latest scientific evidence and clinical guidelines, in order to help optimize and homogenize the treatment of patients with T2D in Primary Care (PC) in Spain. MATERIAL AND METHODS 240 family doctors responded to an online questionnaire about the management of 6 patient profiles with T2D of increasing complexity. RESULTS The main drivers for the antihyperglycemic treatment choice are an HbA1c>10% and the presence of cardiovascular disease (CVD), although in evolved patients, the estimated glomerular filtration rate and the risk of hypoglycemia become more relevant. In newly diagnosed patients with an HbA1c>9%, treatment is still initiated with monotherapy (24%). In patients not controlled with metformin, dipeptidyl peptidase 4 inhibitors (DPP4-I, 54%) or sodium-glucose cotransporter 2 inhibitors (SGLT2-I, 39%) are usually added. On the other hand, type1 glucagon-like peptide receptor agonists (GLP1-RA) are mainly associated with obese patients with T2D. In patients not controlled with metformin+sulfonylurea (SU), SU replacement is preferred to adding a third antihyperglycemic agent to background therapy (77% vs. 23%). CONCLUSIONS T2D treatment in PC is still focused on HbA1c reduction and treatment safety. Thus, DPP4-I are widely used. SGLT2-I are usually preferred for patients with T2D and CVD and GLP1-RA for patients with T2D and obesity, although their use in PC is low.
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17
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Singh AK, Singh R, Chakraborty PP. Diabetes Monotherapies versus Metformin-Based Combination Therapy for the Treatment of Type 2 Diabetes. Int J Gen Med 2021; 14:3833-3848. [PMID: 34335049 PMCID: PMC8318007 DOI: 10.2147/ijgm.s295459] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 07/13/2021] [Indexed: 02/05/2023] Open
Abstract
Step-wise addition of antihyperglycemic agents (AHA) after the initiation of metformin monotherapy has been the traditional approach for the treatment of type 2 diabetes mellitus (T2DM) world-wide. Emerging evidence increasingly suggests that metformin-based combination therapy, especially with the newer AHA that lowers HbA1c glucose-dependently and do not potentiate hypoglycemia, could be a potentially better option for durable glycemic control with good tolerability compared to diabetes monotherapy. In this review, we descriptively analyzed the evidence available from the systematic reviews and meta-analyses of randomized head-to-head trials that reported the efficacy and safety outcomes of diabetes monotherapy, metformin-based combination therapies, and monotherapy versus metformin-based combination therapies.
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Affiliation(s)
- Awadhesh K Singh
- Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, Kolkata, India
| | - Ritu Singh
- Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, Kolkata, India
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18
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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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Hu C, Wang P, Yang Y, Li J, Jiao X, Yu H, Wei Y, Li J, Qin Y. Chronic Intermittent Hypoxia Participates in the Pathogenesis of Atherosclerosis and Perturbs the Formation of Intestinal Microbiota. Front Cell Infect Microbiol 2021; 11:560201. [PMID: 34277461 PMCID: PMC8281814 DOI: 10.3389/fcimb.2021.560201] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 04/21/2021] [Indexed: 11/13/2022] Open
Abstract
Chronic intermittent hypoxia (CIH) is the prominent signature of highly prevalent obstructive sleep apnea (OSA) pathophysiology, which leads to increased risk and aggravation of atherosclerotic cardiovascular diseases. However, whether intestinal microbiota is implicated in the mechanisms linking CIH to arteriosclerosis (AS) pathogenesis remains unclear. The association of CIH with the development of altered gut microbiota (GM) may provide the opportunity to develop preventive strategies for atherosclerotic cardiovascular risk reduction. Animal models of apolipoprotein E-deficient (apoE-/-) mice treated with high-fat diet (HFD) and subjected to CIH conditions was applied to mimic the AS observed in patients with OSA. The physiological status and atherosclerotic lesion formation were confirmed by histological analysis. 16S rDNA sequencing of fecal samples was conducted to determine the changes in gut microbial composition. Morphometric analysis demonstrated that CIH caused aggravated atherosclerotic lesions and facilitated AS in apoE-/- mice treated with HFD. The gut bacteria was significantly varied in AS and AS+CIH mice compared with that in the control mice. Significantly perturbed GM profiles were detected in AS mice with and without CIH, with altered microbial α- and β- diversity and shifts in bacterial compositions at phylum and genus levels. While the difference between AS and AS+CIH was observed at different bacteria taxa levels. Aggravation of reduced Sutterella and increased Halomonas, Halomonadaceae and Oceanospirillales was noted in CIH-treated AS mice. The correlation of intestinal bacterial parameters with pathological changes in artery indicated complicated interactions under CIH-induced GM dysbiosis. Furthermore, the gut microbial functions in the potential ability of replication recombination and repair proteins, glycan biosynthesis and metabolism, as well as metabolism of cofactors and vitamins were identified to be further suppressed by CIH. Our findings demonstrated a causal effect of CIH on GM alterations in AS mice and suggested that the disordered GM features in AS development were deteriorated by CIH, which may be associated with AS aggravation. Preventative strategies targeting gut microbiome are highly recommended for intervention of OSA-related AS.
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Affiliation(s)
- Chaowei Hu
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
| | - Pan Wang
- Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yunyun Yang
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.,Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
| | - Juan Li
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.,Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
| | - Xiaolu Jiao
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.,Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
| | - Huahui Yu
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.,Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
| | - Yongxiang Wei
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.,Otolaryngological Department of Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jing Li
- Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yanwen Qin
- Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.,Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
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20
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Bae JH, Park EG, Kim S, Kim SG, Hahn S, Kim NH. Comparative Renal Effects of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter 2 Inhibitors on Individual Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis. Endocrinol Metab (Seoul) 2021; 36:388-400. [PMID: 33789035 PMCID: PMC8090474 DOI: 10.3803/enm.2020.912] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 01/14/2021] [Accepted: 02/15/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND To compare the renal effects of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual outcomes in patients with type 2 diabetes. METHODS We searched electronic databases (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) from inception to June 2019 to identity eligible randomized controlled trials of DPP-4 inhibitors or SGLT2 inhibitors that reported at least one kidney outcome in patients with type 2 diabetes. Outcomes of interest were microalbuminuria, macroalbuminuria, worsening nephropathy, and end-stage kidney disease (ESKD). We performed an arm-based network meta-analysis using Bayesian methods and calculated absolute risks and rank probabilities of each treatment for the outcomes. RESULTS Seventeen studies with 87,263 patients were included. SGLT2 inhibitors significantly lowered the risks of individual kidney outcomes, including microalbuminuria (odds ratio [OR], 0.64; 95% credible interval [CrI], 0.41 to 0.93), macroalbuminuria (OR, 0.48; 95% CrI, 0.24 to 0.72), worsening nephropathy (OR, 0.65; 95% CrI, 0.44 to 0.91), and ESKD (OR, 0.65; 95% CrI, 0.46 to 0.98) as compared with placebo. However, DPP-4 inhibitors did not lower the risks. SGLT2 inhibitors were considerably associated with higher absolute risk reductions in all kidney outcomes than DPP-4 inhibitors, although the benefits were statistically insignificant. The rank probabilities showed that SGLT2 inhibitors were better treatments for lowering the risk of albuminuria and ESKD than placebo or DPP-4 inhibitors. CONCLUSION SGLT2 inhibitors were superior to DPP-4 inhibitors in reducing the risk of albuminuria and ESKD in patients with type 2 diabetes.
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Affiliation(s)
- Jae Hyun Bae
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul,
Korea
| | - Eun-Gee Park
- Interdisciplinary Program in Medical Informatics, Seoul National University College of Medicine, Seoul,
Korea
| | - Sunhee Kim
- Interdisciplinary Program in Medical Informatics, Seoul National University College of Medicine, Seoul,
Korea
| | - Sin Gon Kim
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul,
Korea
| | - Seokyung Hahn
- Division of Medical Statistics, Medical Research Collaborating Center, Seoul National University Hospital, Seoul,
Korea
- Department of Human Systems Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Institute of Health Policy and Management, Medical Research Center, Seoul National University, Seoul,
Korea
| | - Nam Hoon Kim
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul,
Korea
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21
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Zhou G, Liu L, Li X, Hou X, Wang L, Sun R, Huang H, Li Z, Li W, Wang C, Ba Y. ESRα Promoter Methylation May Modify the Association Between Lipid Metabolism and Type 2 Diabetes in Chinese Farmers. Front Public Health 2021; 9:578134. [PMID: 33748055 PMCID: PMC7969800 DOI: 10.3389/fpubh.2021.578134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 02/08/2021] [Indexed: 11/13/2022] Open
Abstract
Objective: This study is aimed to explore the potential association among the estrogen receptor alpha (ESRα) promoter methylation, lipid metabolism and the risk of type 2 diabetes mellitus (T2DM). Methods: A total of 1143 rural residents were recruited randomly from Henan Province, China. The circulating methylation levels in ESRα promoter region were determined by quantitative methylation-specific polymerase chain reaction. Serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting plasma-glucose (FPG) were measured. Results: The ESRα promoter methylation levels were negatively associated with HDL-C levels whether gender stratification was performed (P < 0.05) and positively correlated with LDL-C in men (P < 0.05). Each unit standard deviation (SD) increment in TG was associated with a 43% increase (95% CI: 1.25, 1.64) in the risks of T2DM in all participants, a 36% increase (95% CI: 1.13, 1.64) in the risks of T2DM in men and a 49% increase (95% CI: 1.21, 1.83) in the risks of T2DM in women. Furthermore, each SD increment in HDL-C was associated with a reduction of 25% (OR = 0.75, 95% CI: 0.58, 0.97) in the risks of T2DM in men, and the risk of T2DM in men may be more susceptible to HDL-C than that in women (P for interaction < 0.05). Additionally, we found that the risk of T2DM in participants with lower methylation levels (≤4.07%) were more susceptible to HDL-C (P for interaction < 0.05). Conclusions: These findings suggested that lipid metabolism was associated with ESRα promoter methylation levels and the risk of T2DM. Besides, the levels of ESRα promoter methylation and gender can modify the association of HDL-C and T2DM.
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Affiliation(s)
- Guoyu Zhou
- Department of Environment Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, China.,Yellow River Institute for Ecological Protection & Regional Coordinated Development, Zhengzhou University, Zhengzhou, China
| | - Lihua Liu
- Department of Environment Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xing Li
- Department of Nutrition and Food Health, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xiangbo Hou
- Department of Environment Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Ling Wang
- Department of Nutrition and Food Health, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Renjie Sun
- Department of Environment Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Hui Huang
- Department of Environment Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Zhiyuan Li
- Department of Environment Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Wenjie Li
- Department of Nutrition and Food Health, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Chongjian Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Yue Ba
- Department of Environment Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, China.,Yellow River Institute for Ecological Protection & Regional Coordinated Development, Zhengzhou University, Zhengzhou, China
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22
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Jia S, Wang Z, Han R, Zhang Z, Li Y, Qin X, Zhao M, Xiang R, Yang J. Incretin mimetics and sodium-glucose co-transporter 2 inhibitors as monotherapy or add-on to metformin for treatment of type 2 diabetes: a systematic review and network meta-analysis. Acta Diabetol 2021; 58:5-18. [PMID: 32514989 DOI: 10.1007/s00592-020-01542-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 04/27/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Although there are many different methods of treating type 2 diabetes (T2D), it is still difficult to draw coincident conclusions concerning the efficacy and safety of different classes of new drugs, and the recommendation level of them has still kept uncertain as second anti-diabetic agents. Therefore, the aim of this study was to summarize evidence on the efficacy and safety of DPP-4is, GLP-1RAs and SGLT-2is as monotherapy or add-on to metformin (Met) for treatment of T2D. MATERIALS AND METHODS We searched PubMed, Embase, Cochrane library and ClinicalTrials.gov for relevant articles in keeping with established methods using terms associated with anti-diabetic agents up to February, 2020, with no start date restriction. Weighted mean difference and risk ratios with 95% confidence intervals were calculated within traditional and network meta-analysis. Primary outcomes were the mean change in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) change and the frequency of hypoglycemic events from baseline after 12 weeks of treatment. RESULTS In total, 64 eligible studies comprising 37,780 patients and 7 treatment strategies were included. The results of primary outcomes showed that GLP-1RAs were significantly more effective than DPP-4is or SGLT-2is in reducing HbA1c when add-on to Met. For FPG, both GLP-1RAs and SGLT-2is significantly reduced FPG compared with DPP-4is whether add-on to Met or not. For hypoglycemia, monotherapy has a lower risk than combination therapy except for SGLT-2is. Ranking probability analysis indicated that GLP-1RAs and SGLT-2is, respectively, reduced HbA1c and FPG most when add-on to Met. Meanwhile, GLP-1RAs took the lowest risk to induce the hypoglycemia, whereas GLP-1RAs plus Met the highest. CONCLUSIONS Both GLP-1RAs and SGLT-2is have their own advantages in efficacy and safety. Monotherapy is beneficial for reducing the risk of hypoglycemia. The recommendation should be a patient-centered approach when selecting treatment choices.
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Affiliation(s)
- Shubing Jia
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Zhiying Wang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Ruobing Han
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Zinv Zhang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Yuping Li
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Xiaotong Qin
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Mingyi Zhao
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Rongwu Xiang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Jingyu Yang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
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Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors. Chronic Dis Transl Med 2020; 6:239-245. [PMID: 33336169 PMCID: PMC7729105 DOI: 10.1016/j.cdtm.2020.07.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Indexed: 02/06/2023] Open
Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are a new type of drug for the treatment of diabetes, and they have been proven to have a good hypoglycemic effect. Several lines of clinical evidence have shown that SGLT2 inhibitors can significantly reduce the risks of atherosclerosis, hospitalization for heart failure, cardiovascular death, and all-cause mortality and delay the progression of chronic kidney disease. Because of the protective effects of SGLT2 inhibitors on the heart and kidney, they are being studied for the treatment of heart failure and chronic kidney disease in patients without diabetes. Therefore, it is necessary for cardiologists, patients with diabetes, and nephrologists to fully understand this type of drug. In this review, we summarize the following three aspects of SGLT2 inhibitors: the recent clinical evidence of their cardiovascular benefits, their mechanisms of action, and their safety.
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24
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Napoli R, Formoso G, Piro S, Targher G, Consoli A, Purrello F. Management of type 2 diabetes for prevention of cardiovascular disease. An expert opinion of the Italian Diabetes Society. Nutr Metab Cardiovasc Dis 2020; 30:1926-1936. [PMID: 32928628 DOI: 10.1016/j.numecd.2020.07.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/07/2020] [Accepted: 07/10/2020] [Indexed: 12/28/2022]
Abstract
AIMS Type 2 diabetes mellitus is characterized by an increased risk of developing long-term cardiovascular complications. Several underlying mechanisms have been proposed for the diabetes-related increase in cardiovascular risk, i.e. chronic hyperglycemia, duration of the disease, drug-induced hypoglycemia, coexistence of multiple cardiovascular risk factors, etc. In the last few years, new pharmacological approaches capable of treating chronic hyperglycemia without increasing the risk of hypoglycemia have emerged for the treatment of diabetes. DATA SYNTHESIS With data mainly obtained from randomized controlled trials recruiting patients with type 2 diabetes in secondary prevention of cardiovascular disease, some of these newer antihyperglycemic drugs have shown to significantly reduce the risk of cardiovascular disease. In addition, the combined control of traditional cardiovascular risk factors, e.g. dyslipidemia, hypertension, etc., has demonstrated to be effective in reducing the burden of cardiovascular diseases in patients with type 2 diabetes. CONCLUSIONS In this document written by some experts of the Italian diabetes society (SID), we will focus our attention on oral antihyperglycemic agents for people with type 2 diabetes in primary or secondary prevention of cardiovascular disease, excluding for brevity the injection therapies for diabetes, such as insulin and glucagon-like peptide-1 receptor agonists.
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Affiliation(s)
- Raffaele Napoli
- Department of Translational Medical Sciences, Internal Medicine and Diabetes, Federico II University School of Medicine, Napoli, Italy.
| | - Gloria Formoso
- Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST, ex CeSI-Met), G. d'Annunzio University, Chieti-Pescara, Italy
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Agostino Consoli
- Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST, ex CeSI-Met), G. d'Annunzio University, Chieti-Pescara, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy
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25
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Scheen AJ. Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 2020; 16:556-577. [PMID: 32855502 DOI: 10.1038/s41574-020-0392-2] [Citation(s) in RCA: 168] [Impact Index Per Article: 33.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/03/2020] [Indexed: 02/07/2023]
Abstract
The management of type 2 diabetes mellitus (T2DM) is becoming increasingly complex. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are the newest antidiabetic agents for T2DM. By targeting the kidney, they have a unique mechanism of action, which results in enhanced glucosuria, osmotic diuresis and natriuresis, thereby improving glucose control with a limited risk of hypoglycaemia and exerting additional positive effects such as weight loss and the lowering of blood pressure. Several outcome studies with canagliflozin, dapagliflozin or empagliflozin reported a statistically significant reduction in major cardiovascular events, hospitalization for heart failure and progression to advanced renal disease in patients with T2DM who have established atherosclerotic cardiovascular disease, several cardiovascular risk factors, albuminuric mild to moderate chronic kidney disease or heart failure. Current guidelines proposed a new paradigm in the management of T2DM, with a preferential place for SGLT2is, after metformin, in patients with atherosclerotic cardiovascular disease, heart failure and progressive kidney disease. Ongoing trials might extend the therapeutic potential of SGLT2is in patients with, but also without, T2DM. This Review provides an update of the current knowledge on SGLT2is, moving from their use as glucose-lowering medications to their new positioning as cardiovascular and renal protective agents.
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Affiliation(s)
- André J Scheen
- Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium.
- Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.
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26
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Effects of Secretome from Fat Tissues on Ion Currents of Cardiomyocyte Modulated by Sodium-Glucose Transporter 2 Inhibitor. Molecules 2020; 25:molecules25163606. [PMID: 32784369 PMCID: PMC7465695 DOI: 10.3390/molecules25163606] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 08/03/2020] [Accepted: 08/06/2020] [Indexed: 12/14/2022] Open
Abstract
Sodium-glucose transporter 2 (SGLT2) inhibitors were shown to decrease mortality from cardiovascular diseases in the EMPA-REG trial. However, the effects of empagliflozin (EMPA) for cardiac arrhythmia are not yet clarified. A total of 20 C57BL/6J mice were divided into four groups: (1) The control group were fed standard chow, (2) the metabolic syndrome (MS) group were fed a high-fat diet, (3) the empagliflozin (EMPA) group were fed a high-fat diet and empagliflozin 10 mg/kg daily, and (4) the glibenclamide (GLI) group were fed a high-fat diet and glibenclamide 0.6 mg/kg daily. All mice were sacrificed after 16 weeks of feeding. H9c2 cells were treated with adipocytokines from the pericardial and peripheral fat from the study groups. The delayed-rectifier potassium current (IK) and L-type calcium channel current (ICa,L) were measured by the whole-cell patch clamp techniques. Adipocytokines from the peripheral and pericardial fat tissues of mice with MS could decrease the IK and increase the ICa,L of cardiomyocytes. After treating adipocytokines from pericardial fat, the IK in the EMPA and GLI groups were significantly higher than that in the MS group. The IK of the EMPA group was also significantly higher than the GLI group. The ICa,L of the EMPA and GLI groups were significantly decreased overload compared with that of the MS group. However, there was no significant difference of IK and ICa,L among study groups after treating adipocytokines from peripheral fat. Adipocytokines from pericardial fat but not peripheral fat tissues after EMPA therapy attenuated the effects of IK decreasing and ICa,L increasing in the MS cardiomyocytes, which may contribute to anti-arrhythmic mechanisms of sodium-glucose transporter 2 (SGLT2) inhibitors.
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27
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Scheen AJ. SGLT2 Inhibitors as Add-On Therapy to Metformin for People with Type 2 Diabetes: A Review of Placebo-Controlled Trials in Asian versus Non-Asian Patients. Diabetes Metab Syndr Obes 2020; 13:2765-2779. [PMID: 32821142 PMCID: PMC7417649 DOI: 10.2147/dmso.s193528] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 07/08/2020] [Indexed: 12/13/2022] Open
Abstract
Metformin remains the first pharmacological choice for treating hyperglycemia in type 2 diabetes (T2DM) in most international guidelines. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are increasingly used as add-on therapy. T2DM pathophysiology is different in Asian and non-Asian (mainly Caucasian) patients. The aim of this systematic review is to compare the efficacy of SGLT2is vs placebo added to metformin in randomized controlled trials (RCTs: range 12-52 weeks) in Asian versus non-Asian patients with T2DM. The primary endpoint is the reduction in glycated hemoglobin (HbA1c) from baseline and key secondary endpoints are reductions in fasting plasma glucose (FPG), body weight (BW) and systolic blood pressure (SBP). Systematic literature search collected 7 RCTs (3 with 2 doses) in Asian patients (10 analyses, n=1164, iSGLT2: canagliflozin, dapagliflozin, ertugliflozin, ipragliflozin, tofogliflozin)) and 10 RCTs (6 with two doses) in non-Asian patients (16 analyses, n=2482, iSGLT2: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin). Baseline values of HbA1c (7.98±0.19 vs 7.89±0.27%), FPG (8.80 ±0.46 vs 9.11±0.49 mmol/l) and SBP (128.4±1.6 vs 130.2±3.1 mmHg) were not significantly different in Asian vs non-Asian patients, but BW was lower in Asian patients (71.6±4.8 vs 88.0±2.5 kg, p<0.001). The placebo-adjusted weighed mean differences (WMD, 95% CI) were similar in Asian versus non-Asian patients regarding the reductions in HbA1c -0.60 (-0.68, -0.53) % versus -0.54 (-0.59, -0.49) % (p=0.568), FPG -1.37 (-1.53, -1.22) mmol/l vs -1.37 (-1.47, -1.27) mmol/l (p=0.627), BW when expressed in percentage of baseline BW -2.23 (-2.55, -1.90) % vs -2.16 (-2.37, -1.96) % (p=0.324), and SBP -4.53 (-5.53, -3.53) mmHg vs -4.06 (-4.83, -3.29) mmHg) (p=0.223). In conclusion, clinical efficacy of SGLT2i, as an add-on treatment to metformin monotherapy in patients with T2DM, is similar in Asian versus non-Asian patients, despite known ethnic differences in phenotype and pathophysiology of T2DM.
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Affiliation(s)
- André J Scheen
- Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège University, Liège, Belgium
- Clinical Pharmacology Unit, CHU Liège, Center for Interdisciplinary Research on Medicines (CIRM), Liège University, Liège, Belgium
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28
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Patel PM, Vaidya V. Health expenditure and health services utilization comparison of patients with type 2 diabetes on sodium–glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors: evidence from 2015 to 2016 medical expenditure panel survey. JOURNAL OF PHARMACEUTICAL HEALTH SERVICES RESEARCH 2020. [DOI: 10.1111/jphs.12373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Abstract
Objectives
Primary objective of this study was to compare the overall health expenditures of patients with type 2 diabetes on sodium–glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors.
Methods
Two cohorts of type 2 diabetes patients receiving either SGLT2 inhibitor with metformin or DPP4 inhibitor with metformin were identified from 2015 to 2016 Medical Expenditure Panel Survey (MEPS) data. Propensity score matching was used to balance cohorts based on socio-economic status, insulin utilization status, and the Charlson comorbidity score. Patients in SGLT2 inhibitor cohort were matched with patients in DPP4 inhibitor cohort using 1 : 2 ratio on the logit of propensity score using caliper width of 0.1 of the standard deviation of the logit of the propensity score. Expenditure variables were analysed using a generalized linear model with log link function and gamma distribution and adjusted for socio-economic variables. Unadjusted means were obtained using bootstrap.
Results
After propensity score matching, 240 patients were left in the sample with 80 patients in SGLT2 inhibitor cohort and 160 patients in DPP4 inhibitor cohort. Unadjusted average annual total health expenditure was significantly higher in the SGLT2 inhibitor cohort versus DPP4 inhibitor cohort ($17,325 versus $15,702; P value <0.0001). After adjusting for socio-economic factors, overall health expenditure (β = −0.3516; P = 0.0038) was significantly lower in DPP4 inhibitor cohort compared to SGLT2 inhibitor.
Conclusion
SGLT2 inhibitors were associated with significantly higher overall and prescription expenditures compared to DPP4 inhibitors during the study period evaluated. Future studies need to utilize administrative claims data to assess current comparativeness effectiveness trends.
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Affiliation(s)
- Pranav M Patel
- University of Toledo College of Pharmacy – Health Outcomes and Socioeconomic Sciences, Toledo, OH, USA
| | - Varun Vaidya
- University of Toledo College of Pharmacy – Health Outcomes and Socioeconomic Sciences, Toledo, OH, USA
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Wu P, Liu Z, Jiang X, Fang H. An Overview of Prospective Drugs for Type 1 and Type 2 Diabetes. Curr Drug Targets 2020; 21:445-457. [PMID: 31670620 DOI: 10.2174/1389450120666191031104653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 10/07/2019] [Accepted: 10/16/2019] [Indexed: 12/14/2022]
Abstract
Aims:
The aim of this study is to provide an overview of several emerging anti-diabetic
molecules.
Background:
Diabetes is a complex metabolic disorder involving the dysregulation of glucose homeostasis
at various levels. Insulin, which is produced by β-pancreatic cells, is a chief regulator of glucose
metabolism, regulating its consumption within cells, which leads to energy generation or storage as glycogen.
Abnormally low insulin secretion from β-cells, insulin insensitivity, and insulin tolerance lead to
higher plasma glucose levels, resulting in metabolic complications. The last century has witnessed extraordinary
efforts by the scientific community to develop anti-diabetic drugs, and these efforts have resulted
in the discovery of exogenous insulin and various classes of oral anti-diabetic drugs.
Objective:
Despite these exhaustive anti-diabetic pharmaceutical and therapeutic efforts, long-term
glycemic control, hypoglycemic crisis, safety issues, large-scale economic burden and side effects remain
the core problems.
Method:
The last decade has witnessed the development of various new classes of anti-diabetic drugs
with different pharmacokinetic and pharmacodynamic profiles. Details of their FDA approvals and
advantages/disadvantages are summarized in this review.
Results:
The salient features of insulin degludec, sodium-glucose co-transporter 2 inhibitors, glucokinase
activators, fibroblast growth factor 21 receptor agonists, and GLP-1 agonists are discussed.
Conclusion :
In the future, these new anti-diabetic drugs may have broad clinical applicability. Additional
multicenter clinical studies on these new drugs should be conducted.
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Affiliation(s)
- Ping Wu
- Department of Pharmacology, 3rd Affiliated Hospital, Soochow University, Changzhou, Jiangsu Province, China
| | - Zhenyu Liu
- Department of Endocrinology, 3rd Affiliated Hospital, Soochow University, Changzhou, Jiangsu Province, China
| | - Xiaohong Jiang
- Department of Endocrinology, 3rd Affiliated Hospital, Soochow University, Changzhou, Jiangsu Province, China
| | - Hao Fang
- Department of Pharmacology, 3rd Affiliated Hospital, Soochow University, Changzhou, Jiangsu Province, China
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Shao SC, Chang KC, Lin SJ, Chien RN, Hung MJ, Chan YY, Kao Yang YH, Lai ECC. Favorable pleiotropic effects of sodium glucose cotransporter 2 inhibitors: head-to-head comparisons with dipeptidyl peptidase-4 inhibitors in type 2 diabetes patients. Cardiovasc Diabetol 2020; 19:17. [PMID: 32050968 PMCID: PMC7014757 DOI: 10.1186/s12933-020-0990-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 01/16/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Sodium glucose cotransporter 2 (SGLT2) inhibitors have shown greater reductions of cardiovascular event risks than dipeptidyl peptidase-4 (DPP4) inhibitors, whereby possible mechanisms may involve the better pleiotropic effects of SGLT2 inhibitors. However, no published data are currently available to directly compare glycemic and pleiotropic effects in real-world type 2 diabetes patients initiating SGLT2 inhibitors or DPP4 inhibitors. METHOD We conducted a retrospective cohort study by analyzing the Chang Gung Research Database, the largest multi-institutional electronic medical records database in Taiwan. We included patients newly receiving SGLT2 inhibitor or DPP4 inhibitor intensification therapy for type 2 diabetes from 2016 to 2017. We matched SGLT2 inhibitor users to DPP4 inhibitor users (1:4) by propensity scores to ensure comparable characteristics between the groups. We primarily evaluated 1-year post-treatment changes of hemoglobin A1c (HbA1c) after SGLT2 inhibitor or DPP4 inhibitor initiation, using two-tailed independent t-test. We also evaluated post-treatment changes in body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values, associated with SGLT2 inhibitors and DPP4 inhibitors. RESULTS We identified a cohort of 2028 SGLT2 inhibitors and 8112 matched DPP4 inhibitors new users. SGLT2 inhibitors and DPP4 inhibitors showed similar HbA1c reductions (- 1.0 vs. - 1.1%; P = 0.076), but patients receiving SGLT2 inhibitors had greater improvements in body weight (- 1.5 vs. - 1.0 kg; P = 0.008), SBP (- 2.5 vs. - 0.7 mmHg; P < 0.001) and ALT values (- 4.1 vs. - 0.0 U/l; P < 0.001) and smaller declines in eGFR values (- 2.0 vs. - 3.5 ml/min/1.73 m2; P < 0.001) when compared to DPP4 inhibitors. CONCLUSION SGLT2 inhibitors had glucose-lowering effects comparable to those of DPP4 inhibitors but more favorable pleiotropic effects on body weight, ALT and eGFR changes, potentially improving type 2 diabetes patients' cardio-metabolic disease risks.
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Affiliation(s)
- Shih-Chieh Shao
- Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 701 Taiwan
| | - Kai-Cheng Chang
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 701 Taiwan
- Department of Pharmacy, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Swu-Jane Lin
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL USA
| | - Rong-Nan Chien
- Liver Research Unit, Linkou Chang Gung Memorial Hospital and University, Taoyuan, Taiwan
| | - Ming-Jui Hung
- Section of Cardiology, Department of Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yuk-Ying Chan
- Department of Pharmaceutical Materials Management, Chang Gung Medical Foundation, Taoyuan, Taiwan
| | - Yea-Huei Kao Yang
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 701 Taiwan
| | - Edward Chia-Cheng Lai
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 701 Taiwan
- Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan
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31
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Scheen AJ. Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials. DIABETES & METABOLISM 2020; 46:186-196. [PMID: 32007623 DOI: 10.1016/j.diabet.2020.01.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 01/13/2020] [Accepted: 01/18/2020] [Indexed: 12/18/2022]
Abstract
AIMS This study compared the reduction of glycated haemoglobin (HbA1c) with sodium-glucose cotransporter type-2 inhibitors (SGLT2is) vs. dipeptidyl peptidase-4 inhibitors (DPP-4is) as add-ons to metformin in patients with type 2 diabetes mellitus (T2DM), with a specific focus on HbA1c changes according to baseline HbA1c. MATERIALS AND METHODS Electronic databases were scrutinized for randomized controlled trials (RCTs) evaluating the reduction of HbA1c from baseline (Δ HbA1c) with an SGLT2i or DPP-4i in patients with T2DM not well controlled by metformin monotherapy. The endpoint was Δ HbA1c using both indirect and direct comparisons. RESULTS Overall, Δ HbA1c was slightly greater with SGLT2is (-0.80±0.20% from 8.03±0.35%; 44 analyses, 29 RCTs, 15 with two doses, n=9321) than with DPP-4is (-0.71±0.23% from 8.05±0.43%; 61 analyses, 59 RCTs, n=17,914; P=0.0354). When the mean baseline HbA1c was<8% ([64mmol/mol] 7.79±0.15% vs. 7.71±0.23%), Δ HbA1c averaged -0.735±0.17% vs. -0.62±0.16% (P=0.0117) with SGLT2is vs. DPP-4is, respectively. However, this difference vanished when the mean baseline HbA1c was≥8% (-0.87±0.22% from 8.27±0.32% with SGLT2is vs. -0.80±0.24% from 8.35±0.33% with DPP-4is; P=0.2756). The relationship between Δ HbA1c and baseline HbA1c was only slightly stronger with SGLT2is (slope: -0.39, r2=-0.43; P<0.0001) than with DPP-4is (slope: -0.26, r2=-0.25; P<0.0001). CONCLUSION Because of the small difference in Δ HbA1c whatever the baseline HbA1c level with SGLT2is vs. DPP-4is as add-ons to metformin, choosing between these glucose-lowering agents in clinical practice should be based on other efficacy criteria (such as weight and blood pressure changes, cardiovascular and renal protection) or on safety profiles rather than on HbA1c levels.
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Affiliation(s)
- A J Scheen
- Division of diabetes, nutrition and metabolic disorders, department of medicine, CHU Liège, Liège University, Liège, Belgium; Clinical pharmacology unit, Centre for interdisciplinary research on medicines (CIRM), CHU Liège, Liège University, Liège, Belgium.
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32
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McGill JB, Subramanian S. Safety of Sodium-Glucose Co-Transporter 2 Inhibitors. Am J Cardiol 2019; 124 Suppl 1:S45-S52. [PMID: 31741440 DOI: 10.1016/j.amjcard.2019.10.029] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 08/06/2019] [Indexed: 12/17/2022]
Abstract
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have a well-defined safety profile based on data obtained from numerous clinical trials, including cardiovascular outcomes trials (CVOTs) and postmarketing pharmacovigilance reporting. Adverse events including risk of genital mycotic infection and volume depletion-related events are consistent with the mechanism of action of this drug class. However, several emergent (albeit infrequent) serious safety issues have also been reported. In their respective CVOTs, the proportion of patients with reported diabetic ketoacidosis was similar in empagliflozin or canagliflozin compared with their placebo groups, but it was higher for dapagliflozin. Canagliflozin may be associated with an increased risk of bone fracture and lower limb amputation; however, data are inconclusive. There is no evidence linking SGLT2 inhibitors with an increased risk of cancer, but these agents, particularly dapagliflozin, should be used with caution in patients with hematuria or a history of bladder cancer. Postmarketing reports of acute kidney injury have occurred in patients receiving SGLT2 inhibitors, and cases identified in recent CVOTs occurred with similar frequency in SGLT2 inhibitor and placebo groups. Common adverse events associated with SGLT2 inhibitors (such as genital infections or volume depletion) are generally mild and manageable by patients or by primary care physicians, and the risk of rare events (such as ketoacidosis) can be minimized by appropriate patient selection and early recognition of symptoms. When selecting treatment, it is important that clinicians weigh the known risks of SGLT2 inhibitors against their proven benefits, including the reduction of adverse cardiovascular and renal outcomes.
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Affiliation(s)
- Janet B McGill
- Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Mo.
| | - Savitha Subramanian
- Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle
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33
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Seferović PM, Coats AJS, Ponikowski P, Filippatos G, Huelsmann M, Jhund PS, Polovina MM, Komajda M, Seferović J, Sari I, Cosentino F, Ambrosio G, Metra M, Piepoli M, Chioncel O, Lund LH, Thum T, De Boer RA, Mullens W, Lopatin Y, Volterrani M, Hill L, Bauersachs J, Lyon A, Petrie MC, Anker S, Rosano GMC. European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure. Eur J Heart Fail 2019; 22:196-213. [PMID: 31816162 DOI: 10.1002/ejhf.1673] [Citation(s) in RCA: 128] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 10/09/2019] [Accepted: 10/16/2019] [Indexed: 12/26/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose-lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose co-transporter type 2 (SGLT-2) inhibitors]. Regarding safety of DPP-4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP-4 inhibitors. GLP-1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT-2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT-2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose-lowering therapies in patients with HF.
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Affiliation(s)
- Petar M Seferović
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia.,Serbian Academy of Sciences and Arts, Belgrade, Serbia
| | - Andrew J S Coats
- Pharmacology, Centre of Clinical and Experimental Medicine, IRCCS San Raffaele Pisana, Rome, Italy
| | - Piotr Ponikowski
- Centre for Heart Diseases, Wrocław Medical University, Wrocław, Poland
| | - Gerasimos Filippatos
- University of Cyprus Medical School, Nicosia, Cyprus.,Athens University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece
| | - Martin Huelsmann
- Division of Cardiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Pardeep S Jhund
- British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Marija M Polovina
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia.,Department of Cardiology, Clinical Centre of Serbia, Belgrade, Serbia
| | - Michel Komajda
- Institute of Cardiometabolism and Nutrition (ICAN), Pierre et Marie Curie University, Paris VI, La Pitié-Salpétrière Hospital, Paris, France
| | - Jelena Seferović
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia.,Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre, Belgrade, Serbia
| | - Ibrahim Sari
- Department of Cardiology, Faculty of Medicine, Marmara University, Istanbul, Turkey
| | - Francesco Cosentino
- Cardiology Unit, Department of Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
| | | | - Marco Metra
- Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
| | - Massimo Piepoli
- Heart Failure Unit, Cardiology, G. da Saliceto Hospital, Piacenza, Italy
| | - Ovidiu Chioncel
- University of Medicine Carol Davila, Bucharest, Romania.,Emergency Institute for Cardiovascular Diseases, Bucharest, Romania
| | - Lars H Lund
- Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden
| | - Thomas Thum
- Hannover Medical School, Institute of Molecular and Translational Therapeutic Strategies, Hannover, Germany
| | - Rudolf A De Boer
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Wilfried Mullens
- Faculty of Medicine and Life Sciences, BIOMED - Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.,Department of Cardiology, Ziekenhuis Oost, Genk, Belgium
| | - Yuri Lopatin
- Regional Cardiology Centre Volgograd, Volgograd State Medical University, Volgograd, Russia
| | | | - Loreena Hill
- School of Nursing and Midwifery, Queen's University Belfast, Belfast, UK
| | - Johann Bauersachs
- Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany
| | - Alexander Lyon
- National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK
| | - Mark C Petrie
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Stefan Anker
- Department of Cardiology (CVK), Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany
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Chung YR, Ha KH, Lee K, Kim DJ. Effects of sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on diabetic retinopathy and its progression: A real-world Korean study. PLoS One 2019; 14:e0224549. [PMID: 31658289 PMCID: PMC6816558 DOI: 10.1371/journal.pone.0224549] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 10/16/2019] [Indexed: 12/14/2022] Open
Abstract
The sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce the incidence of macrovascular complications of diabetes, while their effect on diabetic retinopathy has not been clarified. We compared the effects of SGLT2is with those of dipeptidyl peptidase-4 inhibitors (DPP4is) on the risk of diabetic retinopathy and its progression in people with type 2 diabetes. We performed a retrospective cohort study among people with type 2 diabetes who started on a SGLT2i or DPP4i from 2014 to 2016 according to the Korean National Health Insurance Service database. Subjects initiated on a SGLT2i or DPP4i were matched on a 1:1 basis according to their propensity scores, and Cox proportional hazards regression models were used to calculate the hazard ratios for the risk of diabetic retinopathy and its progression. After propensity score-matching, 41,430 patients without a history of diabetic retinopathy were identified as new users of a SGLT2i (n = 20,175) or DPP4i (n = 20,175). The hazard ratio (95% CI) for diabetic retinopathy was 0.89 (0.83–0.97) for SGLT2i initiators compared with DPP4i initiators. In patients with a history of diabetic retinopathy (n = 4,663 pairs), there was no significant difference in diabetic retinopathy progression between SGLT2i initiators and DPP4i initiators (hazard ratio 0.94, 95% CI 0.78–1.13). This real-world cohort study showed that SGLT2is might be associated with lower risk of diabetic retinopathy compared with DPP4is. Randomized controlled trials are needed to investigate the long-term effect of SGLT2is in diabetic retinopathy in people with diabetes.
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Affiliation(s)
- Yoo-Ri Chung
- Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea
| | - Kyoung Hwa Ha
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
- Cardiovascular and Metabolic Disease Etiology Research Center, Ajou University School of Medicine, Suwon, Korea
| | - Kihwang Lee
- Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea
- * E-mail: (KL); (DJK)
| | - Dae Jung Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
- Cardiovascular and Metabolic Disease Etiology Research Center, Ajou University School of Medicine, Suwon, Korea
- * E-mail: (KL); (DJK)
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35
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Seo JA. An Age of Sodium-Glucose Cotransporter-2 Inhibitor Priority: Are We Ready? Diabetes Metab J 2019; 43:578-581. [PMID: 31694080 PMCID: PMC6834841 DOI: 10.4093/dmj.2019.0173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
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36
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Esposito K, Longo M, Maiorino MI, Petrizzo M, Gicchino M, Bellastella G, Giugliano D. Metabolic effectiveness of gliflozins and gliptins in the routine clinical practice of patients with type 2 diabetes: preliminary results from GIOIA, a prospective multicentre study. Diabetes Res Clin Pract 2019; 155:107787. [PMID: 31326454 DOI: 10.1016/j.diabres.2019.107787] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/04/2019] [Accepted: 07/09/2019] [Indexed: 02/06/2023]
Abstract
AIMS GIOIA is an ongoing prospective multicentre study aiming to assess the vascular and metabolic effects of SGLT-2 inhibitors (gliflozins) and DPP-4 inhibitors (gliptins) in the routine clinical practice of patients with type 2 diabetes (T2D). Herein we describe the preliminary effectiveness data at 6 months. METHODS SGLT-2i and DPP-4i-naïve adult patients with T2D (N = 301 and 260, respectively), with glycated haemoglobin A1c (A1C) >7%, an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2, on background therapy with metformin, insulin or both, are being followed to evaluate markers of vascular (carotid intima-media thickness), myocardial (myocardial diastolic function) and renal (urinary albumin/creatinine ratio) damage during treatment with SGLT-2i or DPP-4i for a period of 24 months. RESULT At baseline, patients initiated on SGLT-2i are younger (about 6 years) and more heavy (about 7.5 kg), have higher A1C level (0.5% more), a longer diabetes duration and more CV events (20% more) than patients initiated on DPP-4i. At 6 months, patients on SGLT-2i (N = 298) and DPP-4i (N = 258) exhibit significant ameliorations in A1C (-1.% and -0.7%, respectively), which were greater (-1.2% and -0.81%) in those on a background metformin treatment only. The composite endpoint (A1C ≤ 7.0% + weight loss ≥ 3 kg) was achieved by 24% and 16% of patients receiving SGLT-2i or DPP-4i, respectively. No unexpected adverse events were reported. CONCLUSIONS Both SGLT-2i and DPP-4i provide substantial improvements in metabolic parameters in the usual clinical practice of T2D, especially when used as second-line treatment.
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Affiliation(s)
- Katherine Esposito
- Diabetes Division, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Miriam Longo
- Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Ida Maiorino
- Diabetes Division, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Michela Petrizzo
- Diabetes Division, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maurizio Gicchino
- Diabetes Division, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giuseppe Bellastella
- Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Dario Giugliano
- Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
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Lamos EM, Hedrington M, Davis SN. An update on the safety and efficacy of oral antidiabetic drugs: DPP-4 inhibitors and SGLT-2 inhibitors. Expert Opin Drug Saf 2019; 18:691-701. [DOI: 10.1080/14740338.2019.1626823] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Elizabeth Mary Lamos
- Division of Endocrinology, Diabetes and Metabolism, University of Maryland School of Medicine, Baltimore,
MD, USA
| | - Maka Hedrington
- Division of Endocrinology, Diabetes and Metabolism, University of Maryland School of Medicine, Baltimore,
MD, USA
| | - Stephen N Davis
- Department of Medicine, University of Maryland Medical Center, Baltimore,
MD, USA
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38
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Singh AK, Unnikrishnan AG, Zargar AH, Kumar A, Das AK, Saboo B, Sinha B, Gangopadhyay KK, Talwalkar PG, Ghosal S, Kalra S, Joshi S, Sharma SK, Sriram U, Mohan V. Evidence-Based Consensus on Positioning of SGLT2i in Type 2 Diabetes Mellitus in Indians. Diabetes Ther 2019; 10:393-428. [PMID: 30706366 PMCID: PMC6437257 DOI: 10.1007/s13300-019-0562-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Indexed: 02/05/2023] Open
Abstract
The current diabetes management strategies not only aim at controlling glycaemic parameters but also necessitate continuous medical care along with multifactorial risk reduction through a comprehensive management concept. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of evolving antidiabetic agents that have the potential to play a pivotal role in the comprehensive management of patients with diabetes due to their diverse beneficial effects. SGLT2i provide moderate glycaemic control, considerable body weight and blood pressure reduction, and thus have the ability to lower the risk of macrovascular and microvascular complications. Some of the unique characteristics associated with SGLT2i, such as reduction in body weight (more visceral fat mass loss than subcutaneous fat loss), reduction in insulin resistance and improvement in β-cell function, as measured by homeostatic model assessment-β (HOMA-β) could be potentially beneficial and help in overcoming some of the challenges faced by Indian patients with diabetes. In addition, a patient-centric approach with individualised treatment during SGLT2i therapy is inevitable in order to reduce diabetic complications and improve quality of life. Despite their broad benefits profile, the risk of genital tract infections, volume depletion, amputations and diabetic ketoacidosis associated with SGLT2i should be carefully monitored. In this compendium, we systematically reviewed the literature from Medline, Cochrane Library, and other relevant databases and attempted to provide evidence-based recommendations for the positioning of SGLT2i in the management of diabetes in the Indian population.Funding: AstraZeneca Pharma India Limited.
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Affiliation(s)
| | | | - Abdul H Zargar
- Advanced Centre for Diabetes and Endocrine Care, Srinagar, Jammu and Kashmir, India
| | - Ajay Kumar
- Diabetes Care and Research Centre, Patna, Bihar, India
| | - Ashok K Das
- Pondicherry Institute of Medical Sciences, Pondicherry, India
| | - Banshi Saboo
- Diacare-Diabetes Care & Hormone Clinic, Ahmedabad, Gujarat, India
| | | | | | | | - Samit Ghosal
- Nightingale Hospital, Kolkata, West Bengal, India
| | - Sanjay Kalra
- Bharti Hospital & B.R.I.D.E, Karnal, Haryana, India
| | - Shashank Joshi
- Lilavati Hospital and Research Centre, Mumbai, Maharashtra, India
| | | | - Usha Sriram
- Clinical Endocrinology Education and Research (ACEER), Chennai, Tamil Nadu, India
| | - Viswanathan Mohan
- Dr Mohan's Diabetes Specialities Centre and Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India
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Dawwas GK, Smith SM, Park H. Cardiovascular outcomes of sodium glucose cotransporter-2 inhibitors in patients with type 2 diabetes. Diabetes Obes Metab 2019; 21:28-36. [PMID: 30039524 DOI: 10.1111/dom.13477] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 07/11/2018] [Accepted: 07/15/2018] [Indexed: 12/27/2022]
Abstract
AIMS To determine the association between cardiovascular diseases (CVD) and SGLT2 inhibitors compared to sulfonylureas and dipeptidyl peptidase-4 (DPP4) inhibitors and to examine within-class effects of SGLT2 inhibitors. METHODS A retrospective cohort analysis was conducted using Truven Health MarketScan. New users of SGLT2 inhibitors, sulfonylureas or DPP-4 inhibitors were included. Primary outcome was incident CVD, defined as non-fatal myocardial infarction or non-fatal stroke; secondary outcomes were hospitalization because of heart failure and lower extremity amputation. Proportional hazards models, after propensity score matching, were used to obtain hazard ratios (HR) and 95% confidence intervals (CI). RESULTS In fully adjusted models, use of SGLT2 inhibitors was associated with a decreased risk of developing CVD compared with use of sulfonylureas (HR, 0.50; 95% CI, 0.45, 0.55) and DPP-4 inhibitors (HR, 0.57; 95% CI, 0.52, 0.62), respectively. Analyses revealed no evidence of within-class effects: dapagliflozin vs sulfonylureas (HR, 0.55; 95% CI, 0.43, 0.70) or DPP-4 inhibitors (HR, 0.57; 95% CI, 0.46, 0.70); and canagliflozin vs sulfonylureas (HR, 0.61; 95% CI, 0.54, 0.69) or DPP-4 inhibitors (HR, 0.66; 95% CI, 0.54, 0.71). Additionally, SGLT2 inhibitors were associated with lower risk of hospitalization because of heart failure compared to both sulfonylureas and DPP-4 inhibitors, as well as lower risk of lower extremity amputation compared to sulfonylureas. CONCLUSION Using population-based data, incident use of SGLT-2 inhibitors was associated with a decreased incidence of CVD compared to use of sulfonylureas and DPP-4 inhibitors. These findings were consistent between dapagliflozin and canagliflozin, suggesting that CVD reduction is a class effect for SGLT2 inhibitors. In addition, SGLT2 inhibitors portended lower risk of hospitalization because of heart failure (vs sulfonylureas and DPP-4 inhibitors) and lower risk of lower extremity amputation (vs sulfonylureas).
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Affiliation(s)
- Ghadeer K Dawwas
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida
| | - Steven M Smith
- Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida
- Department of Community Health and Family Medicine, College of Medicine, University of Florida, Gainesville, Florida
| | - Haesuk Park
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida
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40
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Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2018; 61:2461-2498. [PMID: 30288571 DOI: 10.1007/s00125-018-4729-5] [Citation(s) in RCA: 786] [Impact Index Per Article: 112.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.
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Affiliation(s)
- Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, UK.
- Leicester Diabetes Centre, Leicester General Hospital, Leicester,, LE5 4PW, UK.
| | - David A D'Alessio
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Judith Fradkin
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Walter N Kernan
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Geltrude Mingrone
- Department of Internal Medicine, Catholic University, Rome, Italy
- Diabetes and Nutritional Sciences, King's College London, London, UK
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- University of Copenhagen, Copenhagen, Denmark
| | - Apostolos Tsapas
- Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Deborah J Wexler
- Department of Medicine and Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - John B Buse
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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41
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Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41:2669-2701. [PMID: 30291106 PMCID: PMC6245208 DOI: 10.2337/dci18-0033] [Citation(s) in RCA: 1791] [Impact Index Per Article: 255.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.
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Affiliation(s)
- Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, U.K.,Leicester Diabetes Centre, Leicester General Hospital, Leicester, U.K
| | - David A D'Alessio
- Department of Medicine, Duke University School of Medicine, Durham, NC
| | - Judith Fradkin
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | - Walter N Kernan
- Department of Medicine, Yale School of Medicine, New Haven, CT
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Geltrude Mingrone
- Department of Internal Medicine, Catholic University, Rome, Italy.,Diabetes and Nutritional Sciences, King's College London, London, U.K
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark.,University of Copenhagen, Copenhagen, Denmark
| | - Apostolos Tsapas
- Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Deborah J Wexler
- Department of Medicine and Diabetes Unit, Massachusetts General Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - John B Buse
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
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42
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Lupsa BC, Inzucchi SE. Use of SGLT2 inhibitors in type 2 diabetes: weighing the risks and benefits. Diabetologia 2018; 61:2118-2125. [PMID: 30132031 DOI: 10.1007/s00125-018-4663-6] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 05/08/2018] [Indexed: 12/15/2022]
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors belong to a novel class of glucose-lowering medications that reduce plasma glucose concentrations by inhibiting glucose reabsorption by the kidney, inducing glucosuria. Their actions encompass reductions in HbA1c, fasting and postprandial blood glucose levels, body weight and BP. To date, empagliflozin and canagliflozin have additionally been shown to improve cardiovascular outcomes in high-risk individuals and to slow the progression of diabetic kidney disease. Adverse effects associated with this class include urinary frequency, dehydration, genitourinary tract infections and, rarely, euglycaemic diabetic ketoacidosis. Of the SGLT2 inhibitors, only canagliflozin has been linked to a higher risk of lower-extremity amputations and bone fractures compared with placebo. Optimal prescribing of agents within this relatively new drug category requires a full understanding of their risks in addition to their benefits.
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Affiliation(s)
- Beatrice C Lupsa
- Section of Endocrinology, Yale University School of Medicine, Yale-New Haven Hospital, 333 Cedar Street, FMP 106, P.O. Box 208020, New Haven, CT, 06520, USA
| | - Silvio E Inzucchi
- Section of Endocrinology, Yale University School of Medicine, Yale-New Haven Hospital, 333 Cedar Street, FMP 106, P.O. Box 208020, New Haven, CT, 06520, USA.
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