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Glycaemic variabilities: Key questions in pursuit of clarity. DIABETES & METABOLISM 2021; 47:101283. [PMID: 34547451 DOI: 10.1016/j.diabet.2021.101283] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 09/05/2021] [Indexed: 12/12/2022]
Abstract
After years of intensive investigation, the definition of glycaemic variability remains unclear and the term variability in glucose homoeostasis might be more appropriate covering both short and long-term glycaemic variability. For the latter, we remain in the search of an accurate definition and related targets. Recent work leads us to consider that the within-subject variability of HbA1c calculated from consecutive determinations of HbA1c at regular time-intervals could be the most relevant index for assessing the long-term variability with a threshold value of 5% (%CV = SD of HbA1c/mean HbA1c) to separate stability from lability of HbA1c. Presently, no one can deny that short- and long-term glucose variability should be maintained within their lower ranges to limit the incidence of hypoglycaemia. Usually, therapeutic strategies aimed at reducing post-meal glucose excursions, i.e. the major contributor to daily glucose fluctuations, exert a beneficial effect on the short-term glucose variability. This explains the effectiveness of adjunct therapies with either GLP- receptor agonists or SGLT inhibitors in type 2 diabetes. In type 1 diabetes, the application of a CGM device alone reduces the short-term glycaemic variability. In contrast, sophisticated insulin delivery does not necessarily lead to such reductions despite marked downward shifts of 24-hour glycaemic profiles. Such contrasting observations raise the question as to whether the prolonged wear of CGM devices is or not the major causative factor for improvement in glucose variability among intensively insulin-treated persons with type 1 diabetes.
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Kress S, Borck A, Zisman A, Bramlage P, Siegmund T. A Difference Between Bedtime and Pre-Breakfast Plasma Glucose Levels Indicates the Need for Prandial Insulin in Basal Insulin-Treated Type 2 Diabetic Patients with Normal Fasting Glucose. Diabetes Metab Syndr Obes 2021; 14:1215-1222. [PMID: 33776458 PMCID: PMC7987255 DOI: 10.2147/dmso.s267882] [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: 11/24/2020] [Accepted: 03/04/2021] [Indexed: 11/23/2022] Open
Abstract
AIM In the present analysis, we characterised the efficacy and safety of adding a single daily injection of insulin glulisine to optimised basal-supported oral therapy (BOT) in patients with a high BeAM value, defined as a more than 50 mg/dl difference between bedtime and pre-breakfast blood glucose. METHODS The BeAM value was retrospectively calculated for patients pooled from two clinical trials that supplemented BOT with glulisine. Data regarding changes in HbA1c, fasting plasma glucose (FPG), and postprandial glucose (PPG) levels from observation periods of 3 to 6 months were assessed. RESULTS Out of 358 patients that received BOT/glulisine, 182 had a high BeAM value. Patients with a high BeAM value were older and had a longer diabetes duration than patients with a medium BeAM value. Significant reductions in HbA1c (7.5% to 7.2% [59 to 55 mmol/mol], p<0.0001) and PPG (202 to 143 mg/dl, p<0.0001) levels were documented. The proportion of patients with a high BeAM value achieving an HbA1c <7% [53 mmol/mol], alone or in combination with no hypoglycaemia, was lower than that of patients with a medium BeAM value. CONCLUSION The analysis indicates that the supplementation of BOT with a single daily injection of prandial insulin is safe and effective for reducing HbA1c and PPG levels in patients with a high BeAM value (more than 50 mg/dl). However, patients with a medium BeAM value also responded well, which suggests that they should also be considered candidates for this change in therapy.
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Affiliation(s)
- Stephan Kress
- Diabeteszentrum, Vinzentius-Krankenhaus, Landau, Germany
- Correspondence: Stephan Kress Diabeteszentrum, Vinzentius Krankenhaus, Cornichonstr. 4, Landau, 76829, GermanyTel +49 6341 172208 Email
| | - Anja Borck
- Medical Department, Sanofi, Berlin, Germany
| | - Ariel Zisman
- The Endocrine Center of Aventura, Aventura, FL, USA
| | - Peter Bramlage
- Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany
- Department for Angiology, Brandenburg Medical School, Campus Brandenburg/Havel, Brandenburg, Germany
| | - Thorsten Siegmund
- Diabetes- Hormon- Und Stoffwechselzentrum Am Isar Klinikum München, München, Germany
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Siegmund T, Borck A, Zisman A, Bramlage P, Kress S. A higher blood glucose level pre-breakfast in comparison to bedtime is a contraindication for intensification of prandial insulin therapy in patients with type 2 diabetes - The impact of a negative BeAM value. J Clin Transl Endocrinol 2018; 14:34-38. [PMID: 30416973 PMCID: PMC6214867 DOI: 10.1016/j.jcte.2018.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 09/27/2018] [Accepted: 10/22/2018] [Indexed: 01/21/2023] Open
Abstract
Aims The BeAM value refers to the difference between a patient’s blood glucose level at bedtime (Be) and the following morning before breakfast (AM). The clinical impact of a negative BeAM value (AM blood glucose reading compared to that taken at bedtime) is unknown. Methods T2DM patients of the OPAL and POC trials were pooled and their BeAM values calculated. Results From a total of 358 patients, 31 were calculated as having a negative BeAM value at baseline, while 182 had a high value. Patients in the negative BeAM group were younger, had shorter diabetes duration, and lower HbA1c levels. Fasting blood glucose levels were higher in the negative BeAM group, and these increased to a greater extent during the trial periods. No significant differences in hypoglycaemia occurrence were observed. Multivariate adjusted analysis indicated no association between a negative BeAM value and achievement of HbA1c < 7%, or composite endpoints that additionally included no hypoglycaemia and no weight gain. Conclusions Supplementation of BOT with prandial insulin is not beneficial for patients who have a higher blood glucose reading before breakfast in comparison to before bedtime. Further investigation into the cause of the high morning reading in these patients is indicated.
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Affiliation(s)
- Thorsten Siegmund
- Städt. Klinikum München GmbH, Klinikum Bogenhausen, Germany
- Corresponding author at: Klinik für Endokrinologie, Diabetologie und Angiologie, Klinikum München Bogenhausen, Städt. Klinikum München GmbH, Englschalkinger Straße 77, 81925 München, Germany.
| | - Anja Borck
- Sanofi-Aventis Deutschland GmbH, Berlin, Germany
| | - Ariel Zisman
- The Endocrine Center of Aventura, Aventura, FL, USA
| | - Peter Bramlage
- Institut für Pharmakologie und Präventive Medizin, Cloppenburg, Germany
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The Insulin Regimen That Works. J Dr Nurs Pract 2018; 11:165-168. [PMID: 32745025 DOI: 10.1891/2380-9418.11.2.165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Type 2 diabetes mellitus requires monitoring patients' glycemic control. Treatment must be escalated if glucose levels remain above the recommended goal in patients who are adherent to their current treatment. If glycosylated hemoglobin (HbA1c) levels remain unmet with maximum doses as recommended by the American Diabetes Association (ADA) after adding basal insulin, but fasting blood glucose is at goal, one to three injections daily of rapid-acting insulin are typically added to the treatment plan to be injected prior to meals while continuing all other antihyperglycemic medications. OBJECTIVE To describe an effective method of intensifying insulin therapy based on patients' needs and abilities to self-manage their medications. METHODS We retrospectively reviewed the case of a patient who was referred to the Endocrinology Specialty Clinic for diabetes management. RESULTS Diabetes control was improved after intensifying insulin therapy by adding once-daily rapid-acting insulin injections. CONCLUSIONS Intensifying insulin therapy by adding one dose of rapid-acting insulin prior to meals can improve HbA1c to < 7% in patients on maximum doses of basal insulin whose fasting blood glucose is at goal but whose HbA1c is above goal. IMPLICATIONS FOR NURSING Nurse practitioners must use current care guidelines supported by evidence-based literature to improve patients' outcomes. This case study supports ADA recommendations on early intensification of antihyperglycemic therapy in diabetic patients to decrease the risk of complications by achieving and maintaining HbA1c goals early.
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Ilany J, Bhandari H, Nabriski D, Toledano Y, Konvalina N, Cohen O. Effect of prandial treatment timing adjustment, based on continuous glucose monitoring, in patients with type 2 diabetes uncontrolled with once-daily basal insulin: A randomized, phase IV study. Diabetes Obes Metab 2018; 20:1186-1192. [PMID: 29316176 PMCID: PMC5947685 DOI: 10.1111/dom.13214] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 12/25/2017] [Accepted: 12/25/2017] [Indexed: 12/16/2022]
Abstract
AIMS To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily basal insulin glargine. MATERIALS AND METHODS This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG < 130 mg/dL were randomized (1:1) to either arm A (no sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage. RESULTS A total of 121 patients were randomized to arm A (n = 61) or arm B (n = 60). There was no difference in mean HbA1c at week 24 between arms A and B (8.5% ± 1.2% vs 8.4% ± 1.0%; P = .66). The prandial insulin glulisine dosage for arm A and arm B was 9.3 and 10.1 units, respectively (P = .39). The frequency of hypoglycaemic events did not differ between study arms (36.1% vs 51.7%; P = .08). CONCLUSION Using a CGM sensor to identify the meal with the highest glucose excursion and adjusting the timing of prandial insulin treatment did not show any advantage in terms of glycaemic control or safety in our patients.
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Affiliation(s)
- Jacob Ilany
- Institute of Endocrinology, Sheba MCRamat‐GannIsrael
| | | | - Dan Nabriski
- Endocrine Unit, Meir MC, Clalit Health FundKfar‐SabaIsrael
| | | | - Noa Konvalina
- Institute of Endocrinology, Sheba MCRamat‐GannIsrael
| | - Ohad Cohen
- Institute of Endocrinology, Sheba MCRamat‐GannIsrael
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Johnson EL, Frias JP, Trujillo JM. Anticipatory guidance in type 2 diabetes to improve disease management; next steps after basal insulin. Postgrad Med 2018; 130:365-374. [PMID: 29569978 DOI: 10.1080/00325481.2018.1452515] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The alarming rise in the number of people living with type 2 diabetes (T2D) presents primary care physicians with increasing challenges associated with long-term chronic disease care. Studies have shown that the majority of patients are not achieving or maintaining glycemic goals, putting them at risk of a wide range of diabetes-related complications. Disease- and self-management programs have been shown to help patients improve their glycemic control, and are likely to be of particular benefit for patients with diabetes dealing with these issues. Anticipatory guidance is an individualized, proactive approach to patient education and counseling by a health-care professional to support patients in better coping with problems before they arise. It has been shown to improve disease outcomes in a variety of chronic conditions, including diabetes. While important at all stages, anticipatory guidance may be of particular importance during changes in treatment regimens, and especially during transition to, and escalation of, insulin-based regimens. The aim of this article is to provide advice to physicians on anticipatory guidance for basal-insulin dosing, focusing on appropriate basal-insulin-dose increase and prevention of potentially deleterious basal-insulin doses, so called overbasalization. It also provides an overview of new treatment options for patients with T2D who are not well controlled on basal-insulin therapy, fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists, and advice on the type of anticipatory guidance needed to ensure safe and appropriate switching to these therapies.
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Affiliation(s)
- Eric L Johnson
- a Department of Family and Community Medicine , University of North Dakota , Grand Forks , ND , USA
| | - Juan P Frias
- b National Research Institute , Los Angeles , CA , USA
| | - Jennifer M Trujillo
- c Skaggs School of Pharmacy and Pharmaceutical Sciences , University of Colorado , Aurora , CO , USA
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Linjawi S, Lee BW, Tabak Ö, Lövdahl S, Werther S, Abusnana S. A 32-Week Randomized Comparison of Stepwise Insulin Intensification of Biphasic Insulin Aspart (BIAsp 30) Versus Basal-Bolus Therapy in Insulin-Naïve Patients with Type 2 Diabetes. Diabetes Ther 2018; 9:1-11. [PMID: 29129018 PMCID: PMC5801220 DOI: 10.1007/s13300-017-0334-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Indexed: 01/17/2023] Open
Abstract
INTRODUCTION This 32-week, open-label, randomized, parallel-group, multinational trial aimed to compare the efficacy and safety of stepwise insulin intensification of biphasic insulin aspart 30 (BIAsp 30) relative to stepwise intensification of a basal-bolus regimen in insulin-naïve adults with type 2 diabetes (T2D) who continued pretrial treatment with metformin and sulfonylurea. METHODS Adults with T2D were randomized into one of two treatment arms for 32 weeks: (1) BIAsp 30 once daily (OD), with the possibility of stepwise treatment intensification up to BIAsp 30 three times daily (TID); (2) insulin glargine OD, with the possibility of stepwise treatment intensification with insulin aspart up to TID. The primary endpoint was change from baseline in HbA1c after 32 weeks. RESULTS After 32 weeks, the estimated mean change in HbA1c from baseline was statistically significantly lower in the BIAsp 30 arm (- 1.18%) versus basal-bolus (- 1.36%) [estimated treatment difference 0.18%; 95% confidence interval (95% CI) 0.01; 0.36; p < 0.05]. The proportion of patients with HbA1c below 7.0% was statistically significantly lower with BIAsp 30 (42.9%) compared with basal-bolus (56.9%) (odds ratio 0.58; 95% CI 0.37; 0.89; p = 0.01). The overall rate of severe or blood glucose (BG)-confirmed hypoglycemic events was numerically lower for BIAsp 30 compared with basal-bolus, and a statistically significantly lower rate in nocturnal severe or BG-confirmed hypoglycemia in the BIAsp 30 arm relative to basal-bolus was observed: estimated rate ratio 0.32 (95% CI 0.13; 0.79), p = 0.0131. The proportion of patients with adverse events was similar in both treatment arms. CONCLUSION Insulin intensification with BIAsp 30 and basal-bolus showed an improvement in glycemic control; the change in HbA1c was statistically significantly lower for BIAsp 30 compared to basal-bolus. Basal-bolus treatment was accompanied by a numerically, and statistically significantly, higher rate of overall and nocturnal severe or BG-confirmed hypoglycemia, respectively, compared with BIAsp 30. FUNDING Novo Nordisk A/S. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT02453685.
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Affiliation(s)
- Sultan Linjawi
- Coffs Endocrine and Diabetes Service, Coffs Harbour, NSW, Australia.
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Ömür Tabak
- Internal Medicine Clinic, Ministry of Health Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
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Ghosh S, Unnikrishnan AG, Saboo B, Kesavadev J, Aravind SR, Bajaj S, Rajput R, Seshadri K, Verma N, Gupta A, Makkar BM, Saikia M, Kale S, Damodaran S, Dengra A, Eashwar TKM, Maheshwari A, Pendsey S, Phatak SR, Sharma SK, Singh SK, Ramachandran A, Zargar AH, Joshi SR, Sadikot SM. Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes. Diabetes Metab Syndr 2017; 11 Suppl 1:S507-S521. [PMID: 28433618 DOI: 10.1016/j.dsx.2017.03.045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Indexed: 01/27/2023]
Abstract
Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy.
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Affiliation(s)
- Sujoy Ghosh
- Department of Endocrinology and Metabolism, Institute of Post-Graduate Medical Education and Research, Kolkata, India.
| | | | | | | | | | - Sarita Bajaj
- Department of Medicine, Motilal Nehru Medical College, Allahabad, India
| | - Rajesh Rajput
- Department of Endocrinology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, India
| | - Krishna Seshadri
- Department of Endocrinology and Metabolism, Shri Rama Chandra University, Chennai, India
| | | | | | | | | | | | | | - Ashish Dengra
- Mahi Diabetes & Thyroid Care and Research Center, Jabalpur, India
| | | | - Anuj Maheshwari
- Department of Medicine, Babu Banarasi Das University, Lucknow, India
| | | | | | | | - Surya Kumar Singh
- Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | | | - Abdul H Zargar
- Advanced Center for Diabetes and Endocrine Care, Srinagar, India
| | - Shashank R Joshi
- Lilavati and Bhatia Hospital and Grant Medical College, Mumbai, India
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Rodbard HW, Tripathy D, Vidrio Velázquez M, Demissie M, Tamer SC, Piletič M. Adding fast-acting insulin aspart to basal insulin significantly improved glycaemic control in patients with type 2 diabetes: A randomized, 18-week, open-label, phase 3 trial (onset 3). Diabetes Obes Metab 2017; 19:1389-1396. [PMID: 28345792 PMCID: PMC5637905 DOI: 10.1111/dom.12955] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 03/13/2017] [Accepted: 03/22/2017] [Indexed: 11/26/2022]
Abstract
AIM To confirm glycaemic control superiority of mealtime fast-acting insulin aspart (faster aspart) in a basal-bolus (BB) regimen vs basal-only insulin. MATERIALS AND METHODS In this open-label, randomized, 18-week trial (51 sites; 6 countries), adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c] ± SD: 7.9% ± 0.7% [63.1 ± 7.5 mmol/mol]) receiving basal insulin and oral antidiabetic drugs underwent 8-week optimization of prior once-daily basal insulin followed by randomization 1:1 to either a BB regimen with faster aspart (n = 116) or continuation of once-daily basal insulin (n = 120), both with metformin. Primary endpoint was HbA1c change from baseline after 18 weeks of treatment. Secondary endpoints included: postprandial plasma glucose (PPG) change and overall PPG increment (all meals); weight; treatment-emergent adverse events; hypoglycaemic episodes. RESULTS HbA1c decreased from 7.9% (63.2 mmol/mol) to 6.8% (50.7 mmol/mol; BB group) and from 7.9% (63.2 mmol/mol) to 7.7% (60.7 mmol/mol; basal-only group); estimated treatment difference [95% confidence interval] -0.94% [-1.17; -0.72]; -10.3 mmol/mol [-12.8; -7.8]; P < .0001. Reductions from baseline in overall mean 2-hour PPG and overall PPG increment for all meals (self-measured plasma glucose profiles) were statistically significant in favour of BB treatment ( P < .0001). Severe/blood glucose confirmed hypoglycaemia rate (12.8 vs 2.0 episodes per patient-years of exposure), total daily insulin (1.2 vs 0.6 U/kg) and weight gain (1.8 vs 0.2 kg) were greater with BB than with basal-only treatment. CONCLUSIONS In T2D, faster aspart in a BB regimen provided superior glycaemic control as compared with basal-only insulin, but with an increase in the frequency of hypoglycaemia and modest weight gain.
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Affiliation(s)
| | - Devjit Tripathy
- University of Texas Health Science CenterSan AntonioTexas
- Audie L Murphy VA HospitalSan AntonioTexas
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Downie M, Kilov G, Wong J. Initiation and Intensification Strategies in Type 2 Diabetes Management: A Comparison of Basal Plus and Premix Regimens. Diabetes Ther 2016; 7:641-657. [PMID: 27658921 PMCID: PMC5118237 DOI: 10.1007/s13300-016-0199-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Indexed: 12/17/2022] Open
Abstract
The progressive nature of type 2 diabetes (T2D) often results in the need for initiation and subsequent intensification of insulin treatment to achieve glycemic control. The aim of this review is to examine published clinical evidence that has directly compared two recommended treatment approaches in patients with T2D: (1) a 'basal plus' regimen, whereby 1-2 injections of prandial insulin are added to basal insulin; or (2) the use of once- or twice-daily premix insulin analogs, which contain both basal and prandial insulin in a single injection. Broadly, the available evidence suggests that both basal plus and premix regimens are comparable in terms of efficacy and safety when used for insulin initiation in insulin-naïve patients and intensification in patients who have failed on basal insulin; instances of greater glycemic control are observed with premix insulin; however, these are often accompanied by increases in hypoglycemia and/or weight relative to basal plus treatment, and results should be interpreted within the context of total insulin doses used. Relatively low numbers of patients achieved glycemic control when both regimens were used for insulin intensification following failure of basal insulin, suggesting that a full basal-bolus regimen and/or the use of different treatments is clinically indicated in certain patients. In summary, the current review argues that both basal plus and premix insulin regimens are relatively efficacious and safe options for patients with T2D during both insulin initiation in insulin-naïve patients and intensification in patients who have failed on basal insulin. This emphasizes the important role of patient-centered factors in clinical decision-making. FUNDING Novo Nordisk.
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Affiliation(s)
- Michelle Downie
- Department of Endocrinology, Southland Hospital, Invercargill, New Zealand.
| | - Gary Kilov
- Seaport Diabetes Practice, Launceston, Australia
| | - Jencia Wong
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia
- Discipline of Medicine, University of Sydney, Sydney, Australia
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Giugliano D, Sieradzki J, Stefanski A, Gentilella R. Personalized intensification of insulin therapy in type 2 diabetes - does a basal-bolus regimen suit all patients? Curr Med Res Opin 2016; 32:1425-34. [PMID: 27126277 DOI: 10.1080/03007995.2016.1181051] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful.
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Affiliation(s)
- D Giugliano
- a Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging , Second University of Naples , Naples , Italy
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12
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Gross JL, Rojas A, Shah S, Tinahones FJ, Cleall S, Rodríguez A. Efficacy and safety of a premixed versus a basal-plus insulin regimen as intensification for type 2 diabetes by timing of the main meal. Curr Med Res Opin 2016; 32:1109-16. [PMID: 26934128 DOI: 10.1185/03007995.2016.1161609] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To describe the efficacy and safety of premixed insulin lispro protamine suspension 75%/insulin lispro solution 25% (LM25) twice daily (bid) versus basal insulin glargine plus prandial insulin lispro (IGL), both once daily, according to main meal timing. METHODS Data were obtained post hoc from a 24 week, randomized, open-label study comparing LM25 and IGL as insulin intensification in patients with type 2 diabetes inadequately controlled with once daily basal insulin glargine plus metformin and/or pioglitazone (ClinicalTrials.gov identifier: NCT01175824). Patients administered LM25 bid before breakfast and the evening meal, insulin glargine at bedtime and insulin lispro before the day's main meal (meal with the highest 2 hour postprandial glucose level during screening). Patients were grouped by main meal. Changes in glycosylated hemoglobin (HbA1c) and bodyweight were summarized using likelihood-based mixed models; hypoglycemia incidence was compared between treatments using Fisher's exact test. RESULTS Overall, 476 patients (LM25, n = 236; IGL, n = 240) were randomized. In all main meal groups, with both insulin regimens, mean HbA1c significantly decreased from baseline to 24 weeks (p < 0.0001). Patients whose main meal was in the evening had a greater bodyweight increase with LM25 than with IGL (p = 0.015), and a smaller proportion of these patients experienced total (p = 0.027) and nocturnal (p = 0.006) hypoglycemia with LM25 compared with IGL. Patients whose main meal was lunch experienced more nocturnal hypoglycemia with LM25 than with IGL (p = 0.030). Study limitations include that this was a post hoc analysis and no assessments ensured that: SMBG results determined timing of the main meal, each patient's main meal remained unchanged throughout the study, or patients administered insulin lispro with that meal. CONCLUSIONS Glycemic control improved in patients receiving either LM25 or IGL, irrespective of main meal timing. Both regimens can be used in patients with inadequate glycemic control who are in need of insulin intensification.
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Affiliation(s)
- Jorge L Gross
- a Centro de Pesquisas em Diabetes , Porto Alegre , Rio Grande do Sul , Brazil
| | - Arturo Rojas
- b Centro de Diabetes de Coatzacoalcos , Veracruz , México
| | | | - Francisco J Tinahones
- d Hospital Universitario Virgen de la Victoria , Málaga , Spain
- e IBIMA, CIBER Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III , Málaga , Spain
| | - Simon Cleall
- f Eli Lilly and Company , Windlesham , United Kingdom
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LUO XIAOLI, YAN QINGKAI, WANG YAN, FANG HUI, WANG HONGYONG, BAI YUN, ZENG CHUNYU, WANG XUKAI. Association between insulin dosage and insulin usage time, and coronary artery lesions in patients with type 2 diabetes and coronary heart disease. Exp Ther Med 2016; 11:1767-1771. [PMID: 27168800 PMCID: PMC4840504 DOI: 10.3892/etm.2016.3117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Accepted: 02/29/2016] [Indexed: 11/06/2022] Open
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Rodbard HW, Cariou B, Pieber TR, Endahl LA, Zacho J, Cooper JG. Treatment intensification with an insulin degludec (IDeg)/insulin aspart (IAsp) co-formulation twice daily compared with basal IDeg and prandial IAsp in type 2 diabetes: a randomized, controlled phase III trial. Diabetes Obes Metab 2016; 18:274-80. [PMID: 26592732 PMCID: PMC5066701 DOI: 10.1111/dom.12609] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 11/13/2015] [Accepted: 11/16/2015] [Indexed: 01/12/2023]
Abstract
AIMS To evaluate the efficacy and safety of two insulin intensification strategies for patients with type 2 diabetes previously treated with basal insulin--insulin degludec (IDeg) and insulin aspart (IAsp)--administered as a co-formulation (IDegAsp) or as a basal-bolus regimen (IDeg and IAsp in separate injections). METHODS This 26-week, open-label, treat-to-target, phase IIIb, non-inferiority trial randomized patients (1 : 1) to IDegAsp twice daily with main meals (n = 138; IDegAsp group) or IDeg once daily and IAsp 2-4 times daily (n = 136; IDeg+IAsp group). RESULTS After 26 weeks, the mean glycated haemoglobin (HbA1c) level was 7.0% (53 mmol/mol) for the IDegAsp group and 6.8% (51 mmol/mol) for the IDeg+IAsp group (Δ%HbA1c from baseline -1.31 and -1.50%, respectively). The non-inferiority of IDegAsp versus IDeg+IAsp was not confirmed for mean change in HbA1c [estimated treatment difference (ETD) 0.18, 95% confidence interval (CI) -0.04, 0.41; p = non-significant]. No significant differences were observed in the proportion of patients achieving HbA1c <7.0% (56.5 and 59.6%, respectively). IDegAsp treatment resulted in a significantly lower total daily insulin dose, a smaller change in body weight, numerically lower rates of confirmed hypoglycaemia (self-reported plasma glucose <3.1 mmol/l; rate ratio 0.81; p = non-significant), and nocturnal confirmed hypoglycaemic episodes (rate ratio 0.80; p = non-significant) versus IDeg+IAsp. Patient-reported outcome scores for social functioning were significantly higher for IDegAsp versus IDeg+IAsp (ETD 2.2; 95% CI 0.3, 4.1; p < 0.05). CONCLUSIONS Both intensification strategies effectively improved glycaemic control. Although non-inferiority was not confirmed, there were no significant differences between the groups that could affect clinical utility.
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Affiliation(s)
- H W Rodbard
- Endocrine and Metabolic Consultants, Rockville, MD, USA
| | - B Cariou
- Department of Endocrinology, l'Institut du Thorax, Nantes University Hospital, Nantes, France
| | - T R Pieber
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
| | | | - J Zacho
- Novo Nordisk A/S, Søborg, Denmark
| | - J G Cooper
- Department of Medicine, Stavanger University Hospital, Stavanger, Norway
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Landgraf W, Sandow J. Recombinant Human Insulins - Clinical Efficacy and Safety in Diabetes Therapy. EUROPEAN ENDOCRINOLOGY 2016; 12:12-17. [PMID: 29632581 PMCID: PMC5813452 DOI: 10.17925/ee.2016.12.01.12] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 09/02/2015] [Indexed: 01/26/2023]
Abstract
Insulin replacement therapy is the standard of care for patients with type 1 and advanced type 2 diabetes mellitus. Porcine and bovine pancreatic tissue was the source of the hormone for many years, followed by semisynthetic human insulin obtained by modification of animal insulin. With the development of recombinant DNA technology, recombinant (biosynthetic) human insulin became available in large amounts by biosynthesis in microorganisms (Escherichia coli, yeast) providing reliable supplies of the hormone worldwide at affordable costs. The purity and pharmaceutical quality of recombinant human insulin was demonstrated to be superior to animal and semisynthetic insulin and patients with diabetes could be safely and effectively transferred from animal or semisynthetic human insulin to recombinant human insulin with no change expected in insulin dose. The decision for change remains a clinical objective, follow-up after any change of insulin product is recommended to confirm clinical efficacy. This review provides a summary and retrospective assessment of early clinical studies with recombinant insulins (Insuman®, Humulin®, Novolin®).
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Affiliation(s)
- Wolfgang Landgraf
- Medical Affairs Diabetes Division, Sanofi-Aventis Frankfurt, Germany
| | - Juergen Sandow
- Professor, Centre of Pharmacology, Johann-Wolfgang-Goethe University, Frankfurt/Main, Germany
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Lajara R, Davidson JA, Nikkel CC, Morris TL. CLINICAL AND COST-EFFECTIVENESS OF INSULIN DELIVERY WITH V-GO(®) DISPOSABLE INSULIN DELIVERY DEVICE VERSUS MULTIPLE DAILY INJECTIONS IN PATIENTS WITH TYPE 2 DIABETES INADEQUATELY CONTROLLED ON BASAL INSULIN. Endocr Pract 2016; 22:726-35. [PMID: 26866702 DOI: 10.4158/ep151182.or] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To compare two methods of delivering intensified insulin therapy (IIT) in patients with type 2 diabetes inadequately controlled on basal insulin ± concomitant antihyperglycemic agents in a real-world clinical setting. METHODS Data for this retrospective study were obtained using electronic medical records from a large multicenter diabetes system. Records were queried to identify patients transitioned to V-Go(®) disposable insulin delivery device (V-Go) or multiple daily injections (MDI) using an insulin pen to add prandial insulin when A1C was >7% on basal insulin therapy. The primary endpoint was the difference in A1C change using follow-up A1C results. RESULTS A total of 116 patients were evaluated (56 V-Go, 60 MDI). Both groups experienced significant glycemic improvement from similar mean baselines. By 27 weeks, A1C least squares mean change from baseline was -1.98% (-21.6 mmol/mol) with V-Go and -1.34% (-14.6 mmol/mol) with MDI, for a treatment difference of -0.64% (-7.0 mmol/mol; P = .020). Patients using V-Go administered less mean ± SD insulin compared to patients using MDI, 56 ± 17 units/day versus 78 ± 40 units/day (P<.001), respectively. Diabetes-related direct pharmacy costs were lower with V-Go, and the cost inferential from baseline per 1% reduction in A1C was significantly less with V-Go ($118.84 ± $158.55 per patient/month compared to $217.16 ± $251.66 per patient/month with MDI; P = .013). CONCLUSION Progression to IIT resulted in significant glycemic improvement. Insulin delivery with V-Go was associated with a greater reduction in A1C, required less insulin, and proved more cost-effective than administering IIT with MDI. ABBREVIATIONS A1C = glycated hemoglobin ANCOVA = analysis of covariance CI = confidence interval CSII = continuous subcutaneous insulin infusion FPG = fasting plasma glucose IIT = intensified insulin therapy LSM = least squares mean MDI = multiple daily injections T2DM = type 2 diabetes mellitus TDD = total daily dose.
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Rojas A, Sposetti G, Gross JL, Barbieri DE, Duan R, Linetzky B, De Lana JM, Stempa O, Rodriguez A. Insulin lispro low mixture twice daily vs basal insulin glargine once daily and prandial insulin lispro once daily as insulin intensification strategies in patients with type 2 diabetes: Latin American subpopulation analysis of a randomized trial. Diabetol Metab Syndr 2016; 8:69. [PMID: 27660663 PMCID: PMC5027076 DOI: 10.1186/s13098-016-0163-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 07/10/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This post hoc analysis examined the efficacy and safety of twice-daily insulin lispro low mixture (LM25) and once-daily basal insulin glargine plus once-daily prandial insulin lispro (IGL) in a Latin American subpopulation with type 2 diabetes mellitus (T2DM). METHODS A phase 4, randomized, open-label, parallel-arm trial included participants aged 18-75 years with T2DM taking once-daily insulin glargine and stable doses of metformin and/or pioglitazone with glycated hemoglobin (HbA1c) 7.5-10.5 % and fasting plasma glucose ≤121 mg/dL. Participants were randomized 1:1 to receive their stable dose of metformin and/or pioglitazone plus twice-daily LM25 or IGL for 24 weeks. The primary efficacy outcome was change in HbA1c after 24 weeks of treatment. Results from participants in Argentina, Brazil, and Mexico are presented here. RESULTS 162 participants (80 LM25; 82 IGL) with mean ± standard deviation (SD) age = 57.3 ± 9.0 years and body mass index = 31.3 ± 5.2 kg/m(2) were included. Mean ± SD change in HbA1c from baseline to week 24 was -1.5 ± 1.0 % (LM25) and -1.1 ± 1.2 % (IGL). At week 24, 35.1 % (LM25) and 31.6 % (IGL) of participants achieved HbA1c <7.0 %. Mean ± SD weight gain from baseline to week 24 was 2.4 ± 2.9 kg in the LM25 group and 1.0 ± 3.1 kg in the IGL group. The mean ± SD rates of total hypoglycemia per year were 18.9 ± 27.3 (LM25) and 21.6 ± 31.1 (IGL). Rates of treatment-emergent adverse events were 46 % (LM25) and 39 % (IGL). CONCLUSIONS Our results suggest that both LM25 and IGL are viable treatment options for insulin intensification in Latin American patients with T2DM with suboptimal glycemic control on basal insulin glargine. The safety and tolerability profiles of LM25 and IGL are consistent between this Latin American population and the global trial-level population. Trial registration NCT01175824.
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Affiliation(s)
- Arturo Rojas
- Direccion-investigacion, Servicio Medico Nutricional S.C. (Centro de Diabetes de Coatzacoalcos), Revolucion # 522, 96400 Coatzacoalcos, VER México
| | - Georgina Sposetti
- Diabetes and Metabolism Research Department, Head en Instituto de Investigaciones Clínicas, Mar del Plata, Argentina
| | - Jorge L. Gross
- Centro de Pesquisas em Diabetes, Porto Alegre, Rio Grande do Sul Brazil
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Lajara R, Fetchick DA, Morris TL, Nikkel C. Use of V-Go ® Insulin Delivery Device in Patients with Sub-optimally Controlled Diabetes Mellitus: A Retrospective Analysis from a Large Specialized Diabetes System. Diabetes Ther 2015; 6:531-545. [PMID: 26470692 PMCID: PMC4674471 DOI: 10.1007/s13300-015-0138-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Tight glycemic control and timely treatment can improve outcomes in patients with diabetes yet many remain sub-optimally controlled. The objective of the current study was to evaluate the effect of switching patients with sub-optimally controlled diabetes to the V-Go® (Valeritas Inc., Bridgewater, NJ, USA) Disposable Insulin Delivery device. METHODS A retrospective analysis of electronic medical records was conducted to assess patients with sub-optimal glycemic control defined as a glycated hemoglobin (HbA1c) >7%, switched to V-Go. Blood glucose control defined as change from baseline in HbA1c, prescribed insulin doses, body weight, concomitant anti-hyperglycemic agents, and reported hypoglycemia were collected prior to switching to V-Go and during V-Go use. RESULTS Two-hundred and four patients were evaluated during the study period. Overall, there was a significant decrease in HbA1c after switching to V-Go at the 14- and 27-week follow-up visits. The least-squares mean (LSM) change in HbA1c (95% confidence interval) from baseline to 14 weeks was -1.53% (-1.69% to -1.37%; P < 0.001), and from baseline to 27 weeks was -1.79% (-1.97% to -1.61%; P < 0.001). Significant reductions in mean HbA1c were achieved at both visits in all patient subsets: Patients with type 2 and type 1/latent autoimmune diabetes in adults (LADA); patients using insulin at baseline and patients naïve to insulin at baseline. Patients administering insulin at baseline required significantly less insulin on V-Go (86-99 LSM units/day at baseline to 58 LSM units/day at 27 weeks; P < 0.001). Across all patients, reported hypoglycemic events were no more frequent on V-Go than on previous therapy. CONCLUSION V-Go is safe and effective in patients with sub-optimally controlled diabetes requiring insulin therapy. Glycemic control improved significantly, less insulin was required, and hypoglycemic events were similar after patients switched to insulin delivery by V-Go. FUNDING Valeritas, Inc.
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Affiliation(s)
| | | | - Tracy L Morris
- Department of Mathematics and Statistics, University of Central Oklahoma, Edmond, OK, USA
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Prasanna Kumar KM, Shah S, Shah P, Cleall S, Chen S, Uppal S. Insulin lispro low mixture twice daily versus basal insulin glargine once daily and prandial insulin lispro once daily in patients with type 2 diabetes mellitus requiring insulin intensification—a randomized phase IV trial: Indian subpopulation analyses. Int J Diabetes Dev Ctries 2015. [DOI: 10.1007/s13410-015-0387-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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Monnier L, El Azrak A, Lessan N, Rochd D, Colette C, Bonnet F. Ramadan and diabetes: What we see, learn and understand from continuous glucose monitoring. DIABETES & METABOLISM 2015; 41:456-62. [PMID: 26476619 DOI: 10.1016/j.diabet.2015.09.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 09/08/2015] [Accepted: 09/09/2015] [Indexed: 11/29/2022]
Abstract
Abstinence from eating and drinking from dawn to sunset characterizes the holy month of Ramadan. For the 50 million Muslims worldwide with diabetes who adhere to this religious fast, the practice results in marked changes in glucose homoeostasis. The sunset meal (Iftar) that breaks the fasting state is followed by exaggerated surges in blood glucose and sustained overnight hyperglycaemia in cases of nocturnal overfeeding. The predawn meal (Suhoor) frequently results in prolonged glucose decay over the daylight hours. These glycaemic disturbances are particularly marked in insulin-treated patients, in those with unsatisfactory diabetes control during the pre-Ramadan period and in patients who are poorly compliant with lifestyle recommendations. Whether such patients should be exempt from the Islamic fast remains an open debate, which might be partially resolved by long-term controlled studies using the technology of continuous glucose monitoring in large populations of patients with diabetes.
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Affiliation(s)
- L Monnier
- Institute of Clinical Research, University of Montpellier, 641, avenue du Doyen-Giraud, 34093 Montpellier cedex 5, France.
| | - A El Azrak
- Association for Medical Formation G11, 89, boulevard Anfa, 20000 Casablanca, Morocco
| | - N Lessan
- Imperial College London Diabetes Centre, PO Box 48338, Abu Dhabi, United Arab Emirates
| | - D Rochd
- Association for Medical Formation G11, 89, boulevard Anfa, 20000 Casablanca, Morocco
| | - C Colette
- Institute of Clinical Research, University of Montpellier, 641, avenue du Doyen-Giraud, 34093 Montpellier cedex 5, France
| | - F Bonnet
- Department of Endocrinology, University Hospital, 16, boulevard de Bulgarie, 35200 Rennes, France
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Cahn A, Miccoli R, Dardano A, Del Prato S. New forms of insulin and insulin therapies for the treatment of type 2 diabetes. Lancet Diabetes Endocrinol 2015; 3:638-52. [PMID: 26051044 DOI: 10.1016/s2213-8587(15)00097-2] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Revised: 03/18/2015] [Accepted: 03/30/2015] [Indexed: 12/17/2022]
Abstract
Insulin is a common treatment option for many patients with type 2 diabetes, and is generally used late in the natural history of the disease. Its injectable delivery mode, propensity for weight gain and hypoglycaemia, and the paucity of trials assessing the risk-to-safety ratio of early insulin use are major shortcomings associated with its use in patients with type 2 diabetes. Development of new insulins-such as insulin analogues, including long-acting and short-acting insulins-now provide alternative treatment options to human insulin. These novel insulin formulations and innovative insulin delivery methods, such as oral or inhaled insulin, have been developed with the aim to reduce insulin-associated hypoglycaemia, lower intraindividual pharmacokinetic and pharmacodynamic variability, and improve imitation of physiological insulin release. Availability of newer glucose-lowering drugs (such as glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose co-transporter-2 inhibitors) also offers the opportunity for combination treatment; the results of the first trials in this area of research suggest that such treatment might lead to use of reduced insulin doses, less weight gain, and fewer hypoglycaemic episodes than insulin treatment alone. These and future developments will hopefully offer better opportunities for individualisation of insulin treatment for patients with type 2 diabetes.
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Affiliation(s)
- Avivit Cahn
- Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Roberto Miccoli
- Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa, Italy
| | - Angela Dardano
- Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa, Italy
| | - Stefano Del Prato
- Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa, Italy.
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Monnier L, Colette C. Using the respective contributions of postprandial and basal glucose for tailoring treatments in type 2 diabetes. DIABETES & METABOLISM 2015; 41:179-82. [DOI: 10.1016/j.diabet.2015.03.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Accepted: 03/17/2015] [Indexed: 12/27/2022]
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Tran L, Zielinski A, Roach AH, Jende JA, Householder AM, Cole EE, Atway SA, Amornyard M, Accursi ML, Shieh SW, Thompson EE. Pharmacologic Treatment of Type 2 Diabetes. Ann Pharmacother 2015; 49:700-14. [DOI: 10.1177/1060028015573010] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective: To review the oral and injectable pharmacologic treatment options for type 2 diabetes. Data Sources: A literature search was conducted using PubMed electronic database for studies published in English between 1993 and September 2014. Search terms included diabetes mellitus, type 2 diabetes, and the individual name for each antidiabetic medication reviewed. In addition, manual searches were performed for cross-references from publications. Package inserts, United States Food and Drug Administration (FDA) Web site, Institute for Safe Medication Practices Web site, American Diabetes Association Web site and scientific session poster presentations, and individual drug company Web pages were also reviewed. Study Selection and Data Extraction: This review focused on information elucidated over the past 10 years to assist prescribers in choosing optimal therapy based on individual patient characteristics. Studies leading to the approval of or raising safety concerns for the antidiabetic medications reviewed in this article were included. Data Synthesis: In the past 10 years, there have been 4 novel oral antidiabetic medication classes and 10 new injectable agents and insulin products approved by the FDA for the treatment of type 2 diabetes as well as new information regarding the safety and use of several older antidiabetic medication classes. The distinctions were reviewed for each individual agent, and a comparison was completed if there was more than one agent in a particular therapeutic class. Using current information available, select investigational agents in phase III trials or with a pending new drug application were highlighted. Conclusion: There are now 9 distinct oral pharmacologic classes and a variety of insulin and noninsulin injectable medications available for the treatment of type 2 diabetes. Metformin remains the first-line treatment option for most patients. When considering options for alternative or additional treatment, prescribers must weigh the benefits and risks using individual patient characteristics.
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Affiliation(s)
- Linda Tran
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | - Angela Zielinski
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | - Arpi H. Roach
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | - Jennifer A. Jende
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | | | - Emily E. Cole
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | - Shuruq A. Atway
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | - Melinda Amornyard
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | - Mallory L. Accursi
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | - Suzanna W. Shieh
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
| | - Erin E. Thompson
- Chalmers P. Wylie Veterans Affairs Ambulatory Care Center, Columbus, OH, USA
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Similar glucose control with basal-bolus regimen of insulin detemir plus insulin aspart and thrice-daily biphasic insulin aspart 30 in insulin-naive patients with type 2 diabetes: Results of a 50-week randomized clinical trial of stepwise insulin intensification. DIABETES & METABOLISM 2014; 41:223-30. [PMID: 25483023 DOI: 10.1016/j.diabet.2014.11.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 10/31/2014] [Accepted: 11/07/2014] [Indexed: 11/20/2022]
Abstract
OBJECTIVE This study aimed to demonstrate the non-inferiority of 50-week treatment with stepwise insulin intensification of basal-bolus insulin analogues [insulin detemir (IDet) and aspart (IAsp)] versus biphasic insulin aspart 30 (BIAsp30) in insulin-naive type 2 diabetes mellitus (T2DM) patients not controlled by oral glucose-lowering drugs (OGLDs). RESEARCH DESIGN AND METHODS In this open-label multicentre, multinational, randomized, parallel-arm treat-to-target trial, 403 insulin-naive patients with T2DM in four African countries were randomized to either an IDet+IAsp (n = 200) or BIAsp1-2-3 (n = 203) treatment group. Stepwise insulin intensification was performed at the end of 14, 26 and 38 weeks, depending on HbA1c values. The primary endpoint was change in HbA1c after 50 weeks of treatment. Safety variables were hypoglycaemia incidence, occurrence of adverse events and weight gain. RESULTS Non-inferiority of the IDet+IAsp versus BIAsp1-2-3 treatment regimen was demonstrated by their similar HbA1c levels at the end of trial (IDet+IAsp: baseline 8.6%, 50 weeks 7.4%; BIAsp1-2-3: baseline 8.7%, 50 weeks 7.3%; full analysis set difference: 0.1% [95% CI: -0.1, 0.3]; per protocol: 0.2% [95% CI: -0.1, 0.4]). At week 50, 40.3 and 44.9% of patients achieved HbA1c <7.0% with IDet+IAsp and BIAsp1-2-3, respectively. The rate of overall hypoglycaemia during the trial was also similar in both groups (IDet+IAsp: 9.4 events/patient-year; BIAsp1-2-3: 9.8 events/patient-year). CONCLUSION Insulin initiation and intensification using IDet+IAsp was not inferior to BIAsp1-2-3 in insulin-naive patients with T2DM not controlled by OGLDs. Both regimens led to similar reductions in HbA1c values after 50 weeks of treatment.
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Helena WR, Karolicki B. Management of Type 2 Diabetes - Methods for Addition of Prandial to Basal Insulin. EUROPEAN ENDOCRINOLOGY 2014; 10:124-130. [PMID: 29872476 DOI: 10.17925/ee.2014.10.02.124] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Accepted: 08/08/2014] [Indexed: 11/24/2022]
Abstract
As glycaemic control deteriorates with the progression of type 2 diabetes, treatment guidelines advocate starting basal insulin therapy, and then progressing to a basal-bolus regimen as needed. Nevertheless, although timely intensification of therapy is important to minimise the risk of diabetic complications, considerable clinical inertia exists, not only in the initiation of insulin but also in the progression to multiple-dose insulin regimens. One barrier has been the lack of guidance about how to make the transition from basal-only to basal-bolus insulin therapy. In this review, we discuss how data from the recent FullSTEP study, along with other randomised studies, will help to bridge this gap. Prandial boluses can be added to basal insulin in a stepwise manner, using a straightforward, patient-led dose titration approach and simple estimation of which meal to add the initial prandial bolus to. Reducing the complexity of progression to multiple-dose insulin regimens and empowering patients will lessen the burden on clinicians, improve treatment satisfaction and facilitate timely implementation of treatment guidelines.
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Affiliation(s)
- W Rodbard Helena
- Medical Director, Endocrine and Metabolic Consultants, Rockville, Maryland, US
| | - Boris Karolicki
- Medical Director, Novo Nordisk Inc., Princeton, New Jersey, US
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Abstract
BACKGROUND Insulin and incretin agents (dipeptidyl peptidase-4 inhibitors [DPP4is] and glucagon-like peptide-1 receptor agonists [GLP1 RAs]) are second-line treatment options in patients with type 2 diabetes (T2D) not achieving glycemic targets with metformin. Combinations of insulin with incretin agents have been explored in randomized controlled trials (RCTs) and retrospective studies. However, the optimal approach is still elusive; numerous combination regimens can be envisioned, differing in composition and in order of addition. SCOPE A systematic survey was conducted of RCTs testing insulin/DPP4i or insulin/GLP1 RA regimens. PubMed and other online databases were queried using 'insulin' and the names of all incretin agents available in Canada, along with 'combination', 'concomitant', 'concurrent', and 'add-on'. Web of Science and clinicaltrials.gov were searched to identify unpublished trials. FINDINGS Fifteen placebo-controlled or active-comparator RCTs were identified, reporting outcomes for regimens combining insulins and incretin agents available in Canada. DPP4i add-on to insulin therapy (six trials) leads to modest A1c lowering, with weight neutrality. GLP1 RA and insulin combination therapy (GLP1 RA add-on, five trials; insulin add-on, two trials) is associated with significant A1c lowering, with beneficial effects on body weight. A single proof-of-concept trial compared GLP1 RA to DPP4i add-on to insulin, and only one RCT examined simultaneous introduction of an incretin agent with insulin. Adding an incretin agent to established basal insulin therapy may represent a useful alternative to insulin intensification with prandial or premixed insulin. Initial introduction of an incretin agent, with subsequent introduction of insulin, offers potential practical advantages. No study directly comparing order of addition has yet been reported. CONCLUSIONS Insulin/incretin combination therapy comprises a variety of efficacious, weight-sparing regimens and may be considered for many patients who do not achieve glycemic targets when treated with insulin or an incretin agent.
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Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DHW. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol 2014; 2:30-7. [PMID: 24622667 DOI: 10.1016/s2213-8587(13)70090-1] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND We compared stepwise addition of bolus insulin with a full basal-bolus regimen in patients with type 2 diabetes inadequately controlled on basal insulin plus oral antidiabetic drugs. METHODS The FullSTEP study was a phase 4, 32-week, randomised, open-label, two-arm, parallel-group, multinational, treat-to-target, non-inferiority trial done at 150 sites across seven countries to assess the effectiveness of a stepwise dosing approach versus a basal-bolus regimen. In this trial, 401 patients (mean age 59·8 years [SD 9·3]; HbA1c 7·9% [63 mmol/mol]; mean diabetes duration 12·6 years [SD 8·0]) were block randomised (ratio 1:1) to receive either stepwise treatment or full basal-bolus treatment. Patients in the basal-bolus group received insulin aspart before every meal throughout the trial. Patients in the stepwise group received one bolus dose with the largest meal, with additional insulin aspart doses before the next largest meal added to their regimen at 11 weeks and 22 weeks if HbA1c remained at 7% or higher. The primary outcome was non-inferiority of stepwise addition of bolus insulin versus complete basal-bolus therapy, as assessed by change in HbA1c from baseline to 32 weeks (non-inferiority margin of 0·4%). This trial is registered with ClinicalTrials.gov, number NCT01165684. FINDINGS The study was started on Oct 27, 2010, and completed on April 25, 2012. After 32 weeks, HbA1c change from baseline was -0·98% (95% CI -1·09 to -0·87) for the stepwise group and -1·12% (-1·23 to -1·00) for the basal-bolus group; mean treatment difference 0·14 (95% CI -0·02 to 0·30), non-significant (p=0·0876). Fewer hypoglycaemic episodes occurred in the stepwise group than in the basal-bolus group (rate ratio 0·58 [95% CI 0·45 to 0·75]; p<0·0001). Treatment-emergent adverse events did not differ between the two treatment groups. The most frequently reported treatment-emergent adverse event were nasopharyngitis, influenza, diarrhoea, headache, peripheral oedema, and wrong drug given. Three participants died: two before randomisation and one in the basal-bolus group (due to severe acute myocardial infarction and respiratory tract inflammation). INTERPRETATION Stepwise prandial insulin intensification provides glycaemic control non-inferior to a full basal-bolus regimen after 32 weeks, with significantly lower hypoglycaemia risk and better patient satisfaction. FUNDING Novo Nordisk.
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Affiliation(s)
| | | | | | | | - David H W Shu
- Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada
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Hagen SE, Wright DW, Finch R, Talamonti WJ, Edington DW. Impact of compliance to oral hypoglycemic agents on short-term disability costs in an employer population. Popul Health Manag 2013; 17:35-41. [PMID: 23869539 DOI: 10.1089/pop.2013.0009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
This study evaluated the relationships between compliance with oral hypoglycemic agents and health care/short-term disability costs in a large manufacturing company. The retrospective analysis used an observational cohort drawn from active employees of Ford Motor Company. The study population consisted of 4978 individuals who were continuously eligible for 3 years (between 2001-2007) and who received a prescription for an oral hypoglycemic agent during that time. Medical, pharmacy, and short-term disability claims data were obtained from the University of Michigan Health Management Research Center data warehouse. Pharmacy claims/refill data were used to calculate the proportion of days covered (PDC); an individual was classified as compliant if his/her PDC was ≥80%. Model covariates included age, sex, work type, and Charlson comorbidity scores. The impact of compliance on disability and health care costs was measured by comparing the costs of the compliant with those of the noncompliant during a 1-year follow-up. Among these employees, compliant patients had lower medical, higher pharmacy, and lower short-term disability costs than did the noncompliant. After adjusting for demographics and comorbidity, noncompliance was associated with statistically higher short-term disability costs ($1840 vs. $1161, P<0.0001), longer short-term disability duration, and an increase in short-term disability incidence (21.5% of the noncompliant had a claim compared to 16.0% of the compliant, P<0.0001). These results suggest that medication compliance may be important in curtailing the rise of health care/disability costs in the workplace. Employers concerned with the total costs associated with diabetes should not overlook the impact of compliance on short-term disability.
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Affiliation(s)
- Susan E Hagen
- 1 Health Management Research Center, University of Michigan , Ann Arbor, Michigan
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Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice. Gene Ther 2013; 20:1077-84. [DOI: 10.1038/gt.2013.33] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 04/10/2013] [Accepted: 05/15/2013] [Indexed: 12/25/2022]
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