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

OBJECTIVE: To investigate the efficacy and safety of once-daily semaglutide in comparison with once-daily liraglutide and placebo in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This 26-week, multicenter, double-blind trial involved patients diagnosed with type 2 diabetes with HbA_1c 7.0-10.0% (53-86 mmol/mol) and treated with diet and exercise with or without metformin. Patients were randomized 2:2:1 to once-daily semaglutide, liraglutide, or placebo in one of four volume-matched doses (semaglutide 0.05,0.1,0.2, or 0.3 mg and liraglutide 0.3,0.6, 1.2, or 1.8 mg, with both compared within each volume-matched dose group). Primary end point was change in HbA_1c from baseline to week 26. RESULTS: In total, 705 randomized patients were exposed to trial products. At week 26, a dose-dependent change in HbA_1c was observed with semaglutide from 21.1% (0.05 mg) to 21.9% (0.3 mg) and with liraglutide from 20.5% (0.3 mg) to 21.3% (1.8 mg) (all P < 0.001 in favor of volume-matched semaglutide dose). Change with pooled placebo was 20.02% (P < 0.0001 vs. semaglutide). Gastrointestinal (GI) disorders were the most common adverse events (AEs) with semaglutide and liraglutide, occurring in 32.8-54.0% and 21.9-41.5% of patients, respectively. CONCLUSIONS: Once-daily semaglutide at doses up to 0.3 mg/day resulted in greater reductions in HbA_1c compared with liraglutide or placebo but with a higher frequency of GI AEs.