A Review of the Long-Term Efficacy, Tolerability, and Safety of Exenatide Once Weekly for Type 2 Diabetes.

Stefano Genovese,Edoardo Mannucci,Antonio Ceriello

doi:10.1007/s12325-017-0499-6

Abstract

IntroductionExenatide once weekly (ExeOW, Bydureon®, Astra Zeneca), a drug belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists, is the first agent approved for treatment of type 2 diabetes (T2D) that can be administered on a weekly basis.MethodsData concerning treatment of T2D with ExeOW are reviewed with special reference to its long-term efficacy, tolerability, and safety. Relevant literature was identified through the PubMed database from inception to January 2015.ResultsIn randomized clinical trials ExeOW, as add-on to oral antidiabetics, achieved significantly improved glycemic control compared to maximum recommended doses of exenatide twice daily, sitagliptin, pioglitazone, and insulin glargine, as measured by HbA1c. In drug-naïve patients ExeOW was superior to sitagliptin and non-inferior to metformin, whereas non-inferiority to pioglitazone and liraglutide was not proven. In different trials reductions in HbA1c ranged from −1.1% to −2.0%. ExeOW therapy over 6 months was also associated with a mean weight loss of −2 to −4 kg, improved systolic blood pressure and lipid profile, and no hypoglycemia unless associated to sulfonylurea. ExeOW long-term therapy up to 3–6 years allowed persistent glycemic control (HbA1c −1.6%), sustained decreases in blood pressure (−2 mmHg), and improvements of lipid profile. ExeOW tolerability was comparable to that of the other GLP-1 receptor agonists, with better gastrointestinal tolerability when direct comparison was done (namely liraglutide and exenatide BID), but higher incidence of injection site reactions and few treatment discontinuations mainly due to gastrointestinal events.ConclusionExeOW is a well-tolerated and convenient option for long-term treatment of T2D allowing significant and persistent glycemic control with moderate weight loss and low risk of hypoglycemia unless associated with sulfonylureas.

Highlights

Exenatide once weekly (ExeOW, BydureonÒ, Astra Zeneca), a drug belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists, is the first agent approved for treatment of type 2 diabetes (T2D) that can be administered on a weekly basis
Studies for this review were identified through PubMed database searches from inception until January 2015; search terms included GLP-1 receptor agonist, exenatide, slow release, long acting, once week, onceweekly, QW, OW—and other terms that could have been related to individual sections of this review
Additional references were identified manually either from references listed in the studies selected through PubMed or from abstracts presented at 2014 American Diabetes Association (ADA) and European Association of the Studies of Diabetes (EASD) conferences

Summary

INTRODUCTION

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone produced by the intestinal epithelial endocrine L cells through differential processing of proglucagon. GLP-1 is responsible for 50–70% of the total postprandial insulin secretion in a glucose-dependent manner [1]; its action on the pancreatic endocrine system includes stimulation of insulin biosynthesis, reduction of glucagon secretion, modulation of insulin sensitivity of beta cells and, at least in animal models, a positive action on beta cell mass itself [2]. ExeOW is an extended release formulation of exenatide. Exenatide twice daily (ExeBID, ByettaÒ, Astra Zeneca) was the first GLP-1 receptor agonist approved for management of T2D. ExeOW requires only a once-weekly injection as compared to twice-daily injections of the ExeBID formulation. We reviewed data concerning treatment of T2D with ExeOW with special reference to its long-term efficacy, tolerability, and safety

METHODS

Study design

11 NR 5 NR

Findings

CONCLUSION