Semaglutide once per day (up to 0.3 mg) led to more optimal decreases in HbA1c when compared with liraglutide or placebo, but there was a higher rate of gastrointestinal adverse events with use, according to findings from a study published in Diabetes Care.
The action performed by glucagon-like peptide 1 (GLP-1) to restrain gastric emptying and decrease body weight has made it a popular early therapy in the treatment of type 2 diabetes. Because semaglutide is a new GLP-1 analog for people with type 2 diabetes, investigators evaluated its safety and efficacy using wider dose ranges. They also compared its effects to those of liraglutide and placebo.
Using a multicenter, double-blind design, investigators conducted a 26-week trial focused on individuals with type 2 diabetes and HbA1c levels between 7.0-10.0%. Each participant was also “treated with diet and exercise with or without metformin.” The study participants were randomly assigned to once-daily doses of semaglutide, liraglutide, or placebo. Study investigators also used volume-matched doses in the group comparisons. Semaglutide doses were 0.05, 0.1, 0.2, or 0.3 mg per day. Liraglutide doses were 0.3, 0.6, 1.2, or 1.8 mg per day. The primary and secondary study end points were change in HbA1c from baseline to week 26 for semaglutide vs placebo and semaglutide vs liraglutide, respectively.
A total of 705 individuals participated in the trial. For all dose groups, approximately 63 to 65 people were enrolled in each arm with a pooled placebo grouping of 129 participants. The change in baseline HbA1c at 26 weeks was significant for all doses of semaglutide compared with placebo (P <.0001). Researchers also reported significant baseline changes for all volume-matched doses of semaglutide vs liraglutide (P <.001). At week 26, HbA1c target ≤ 6.5% was achieved by 43-73% participants in the semaglutide group, and 6% in the placebo group. There was a dose-dependent mean change in weight observed at week 26 in the semaglutide groups ranging from -2.8 kg (0.05 mg group) to -8.2 kg (0.3 mg group) and in the liraglutide groups ranging from -1.5 kg (0.3 mg group) to -3.7 kg (1.8 mg group).
Adverse events that led to treatment discontinuation were higher in the pooled placebo group (10.9%) than in the semaglutide (6.3-7.9%) and liraglutide (3.1-7.8%) groups. However, gastrointestinal adverse events (nausea, diarrhea, and vomiting) resulted in treatment discontinuations for more semaglutide (1.6-4.7%) than liraglutide (1.6-3.1%) participants.
Study limitations included the short duration of the trial, small treatment arms, and self-reporting of adverse events. Additionally, in this trial, liraglutide was “titrated at a slower rate than label” and this could have an impact on its tolerability and the lower rates of gastrointestinal events observed with its use.
The study authors note that, “semaglutide administered subcutaneously once daily led to significantly greater glycemic control compared with placebo or liraglutide.” However, they caution, “this trial only enrolled individuals who were either treatment naive or treated with metformin; therefore, results should not be extrapolated to patients with more advanced disease.”
This trial was supported by Novo Nordisk. Please refer to reference for a complete list of authors’ disclosures.
Lingvay I, Desouza CV, Lalic KS, et al. A 26-week randomized controlled trial of semaglutide once daily versus liraglutide and placebo in patients with type 2 diabetes suboptimally controlled on diet and exercise with or without metformin [published online July 19, 2018]. Diabetes Care. doi: 10.2337/dc17-2381