Exenatide plus metformin compared with metformin alone on β-cell function in patients with Type 2 diabetes.
ABSTRACT Aim To quantify how much exenatide added to metformin improves β-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone. Methods A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation. Results Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment β-cell function index (HOMA-β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin. Conclusion Exenatide is effective not only on glycaemic control, but also in protecting β-cells and in reducing inflammation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
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ABSTRACT: Glucagon-like peptide-1 (GLP-1) has been evaluated for use in the treatment of type 2 diabetes mellitus (T2DM) due to its role in glucose regulation. Four GLP-1 receptor agonists (RAs) are currently indicated for T2DM in the USA. Exenatide and liraglutide are short-acting and require twice-daily and daily dosing, respectively. Two longer acting agents, exenatide long-acting release (LAR) and albiglutide, were formulated to allow for once-weekly dosing. All four GLP-1 RAs have demonstrated reductions in hemoglobin A1c, fasting blood glucose, and body weight both as monotherapy and in combination with first- and second-line diabetes agents including metformin, sulfonylureas, thiazolidinediones, and insulin. Greater glycemic control was seen with liraglutide compared with the other GLP-1 treatment options; however, the two long-acting agents were superior to exenatide twice daily. All agents were well tolerated with most adverse events being mild or moderate in nature. The most common adverse event was transient nausea which typically resolved 4-8 weeks after treatment initiation. Long-acting agents had lower rates of nausea but an increased incidence of injection site reactions. Trials have suggested GLP-1 RAs may improve cardiovascular risk factors including blood pressure, lipid parameters and inflammatory markers. Future trials are needed to confirm the clinical outcomes of these agents. Overall, GLP-1 RAs will provide benefit for patients with T2DM intolerable to or not reaching glycemic goals with first-line agents, especially in patients in need of weight loss.Therapeutic advances in endocrinology and metabolism 02/2015; 6(1):3-18. DOI:10.1177/2042018814558242
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ABSTRACT: Background The ability of interventions to affect declining β-cell function in screen-detected type 2 diabetes are poorly described. The Early Diabetes Intervention Program (EDIP; ClinicalTrials.gov NCT01470937) was a randomized study based on the hypothesis that improving postprandial glucose excursions with acarbose would slow the progression of fasting hyperglycemia in screen-detected type 2 diabetes. In EDIP, the effect of acarbose plus lifestyle advice on progression of fasting hyperglycemia over a 5 year period was not greater than that of placebo. However, there was an early glucose lowering effect of the trial. The objective of the current secondary analysis was to describe ß-cell function changes in response to glucose-lowering.Methods Participants were overweight adult subjects with screen-detected type 2 diabetes. ß-cell function was measured using hyperglycemic clamps and oral glucose tolerance testing. The primary outcome was the change in ß-cell function from baseline to Year 1, the time point where the maximal glucose-lowering effect was seen.ResultsAt baseline, participants exhibited markedly impaired first-phase insulin response. Despite significant reductions in weight, FPG, and 2-hr PG, there was no clinically significant improvement in first-phase insulin response. Late-phase insulin responses declined despite beneficial glycemic effects of interventions.Conclusions Insulin secretion is already severely impaired in early, screen-detected type 2 diabetes. Effective glucose-lowering intervention with acarbose was not sufficient to improve insulin secretion or halt the decline of β-cell function. This article is protected by copyright. All rights reserved.Diabetes/Metabolism Research and Reviews 11/2014; 30(8). DOI:10.1002/dmrr.2553 · 3.59 Impact Factor
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ABSTRACT: In recent years the treatment focus for type 2 diabetes has shifted to prevention by lifestyle change and to more aggressive reduction of blood sugars during the early stage of treatment. Weight reduction is an important goal for many people with type 2 diabetes. Bariatric surgery is no longer considered a last resort treatment. Glucagon-like peptide-1 agonists given by injection are emerging as a useful treatment since they not only lower blood sugar but are associated with a modest weight reduction. The role of the oral dipeptidyl peptidase 4 inhibitors is emerging as second line treatment ahead of sulphonylureas due to a possible beneficial effect on the beta cell and weight neutrality. Drugs which inhibit glucose re-absorption in the kidney, sodium/glucose co-transport 2 inhibitors, may have a role in the treatment of diabetes. Insulin treatment still remains the cornerstone of treatment in many patients with type 2 diabetes.10/2014; 5(5):636-50. DOI:10.4239/wjd.v5.i5.636