Efficacy and safety of exenatide once weekly: an overview of the DURATION trials

Abstract

Diabetes management involves controlling glycemia and cardiometabolic risk factors. In the DURATION trials, the efficacy and safety of exenatide (EX) once weekly (q.w.), a new long-acting glucagon-like-peptide-1 receptor agonist, was studied as monotherapy or as add-on to metformin with or without sulfonylurea, and compared with oral (metformin, pioglitazone or sitagliptin) and injectable antidiabetic drugs (EX twice daily [EX b.i.d.], liraglutide and insulin glargine). EX q.w. reduced HbA_1c by 1.3–1.9% and showed better overall glycemic control compared with EX b.i.d., sitagliptin, pioglitazone and insulin glargine, but not liraglutide. Fasting plasma glucose was reduced more by EX q.w. than by EX b.i.d. or sitagliptin, whereas postprandial glycemia was better controlled by EX b.i.d. Weight loss was achieved by EX q.w. and EX b.i.d., in contrast to pioglitazone and insulin glargine. EX q.w. improved systolic blood pressure, lipids and cardiovascular risk markers. EX q.w. was well tolerated without safety issues. The most common adverse events were nausea, vomiting and constipation. Injection-site reactions were present in 5–13%. The risk of hypoglycemia of EX q.w. was similar to EX b.i.d., sitagliptin and pioglitazone. Hypoglycemia risk was not increased when EX q.w. was not combined with sulfonylurea.

Keywords::

• diabetes
• DURATION trial
• exenatide
• GLP-1
• incretin

Financial & competing interests disclosure

Literature search was carried out by CEM De Block and LF Van Gaal; the first draft was written by CEM De Block and the critical review resulting in the final manuscript was carried out by both the authors. CEM De Block has served on advisory panels for Abbott, A. Menarini Diagnostics, Eli Lilly and Company, and Novo Nordisk. He has received honoraria as a member of the speaker’s bureau of Abbott, A. Menarini Diagnostics, Eli Lilly and Company, and Sanofi. LF Van Gaal has served on advisory panels and has received honoraria as a member of the speaker’s bureau for Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Janssen Pharma, Merck Sharp and Dohme, Novo Nordisk and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.