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SOURCE: Ahmann AJ, et al. Diabetes Care 2018;41:258-266.
There are more similarities than differences among the seven currently available glucagon-like peptide-1 (GLP-1) receptor agonists. The most recently FDA-approved GLP-1 receptor agonist, once-weekly semaglutide (Ozempic), was compared in a head-to-head trial to once-weekly exenatide-ER (Bydureon).
In this open-label trial, adult subjects with type 2 diabetes (n = 813) taking one or more oral agents were randomized to receive either 1 mg/week of semaglutide or 2 mg/week of exenatide-ER. Subjects taking semaglutide underwent a titration from 0.25 mg/week for four weeks, then 0.5 mg/week for four weeks, and then 1.0 mg/week for the remainder of the trial; exenatide-ER subjects were started on 2.0 mg/week and maintained that dose throughout the trial. Baseline A1c was 8.3% in the exenatide group and 8.4% in the semaglutide group.
At the conclusion of the trial (56 weeks), the clinically meaningful differences in outcomes were the following: A1c was reduced by 1.5% with semaglutide vs. 0.9% with exenatide; weight declined 5.6 kg with semaglutide vs. 1.9 kg with exenatide; the fraction of subjects attaining an A1c < 7.0% was significantly greater with semaglutide (67% vs. 40%). While gastrointestinal adverse events were more common in the semaglutide treatment arm, injection site reactions were more frequent with exenatide. The efficacy advantages of semaglutide over exenatide-ER were both clinically meaningful and statistically significant. Generally, liraglutide has been regarded as the most potent GLP-1 receptor agonist. It will be interesting to see if semaglutide ultimately bests liraglutide, since both agents have demonstrated favorable cardiovascular outcomes in cardiovascular safety trials.
Financial Disclosure: To reveal any potential bias in this publication, and in accordance with Accreditation Council for Continuing Medical Education guidelines, Dr. Brunton reports he is a retained consultant for Abbott Diabetes, Becton Dickinson, Boehringer Ingelheim, Janssen, Lilly, Merck, Novo Nordisk, and Sanofi; he serves on the speakers bureau of AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, and Novo Nordisk. Dr. Kuritzky (author) is a consultant for and on the speakers bureau of Amgen, Boehringer Ingelheim, and Shire. Ms. Coplin, Mr. Springston, and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.