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.