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

Diabetes Care. 2018 Sep;41(9):1926-1937. doi: 10.2337/dc17-2381. Epub 2018 Jul 19.

Abstract

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 HbA1c 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 HbA1c from baseline to week 26.

Results: In total, 705 randomized patients were exposed to trial products. At week 26, a dose-dependent change in HbA1c was observed with semaglutide from -1.1% (0.05 mg) to -1.9% (0.3 mg) and with liraglutide from -0.5% (0.3 mg) to -1.3% (1.8 mg) (all P < 0.001 in favor of volume-matched semaglutide dose). Change with pooled placebo was -0.02% (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 HbA1c compared with liraglutide or placebo but with a higher frequency of GI AEs.

Trial registration: ClinicalTrials.gov NCT02461589.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / therapy
  • Diet*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Exercise / physiology*
  • Female
  • Glucagon-Like Peptides / administration & dosage*
  • Glucagon-Like Peptides / adverse effects
  • Glycated Hemoglobin / analysis
  • Humans
  • Liraglutide / administration & dosage*
  • Liraglutide / adverse effects
  • Male
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Middle Aged
  • Placebos
  • Treatment Outcome

Substances

  • Glycated Hemoglobin A
  • Placebos
  • semaglutide
  • Glucagon-Like Peptides
  • Liraglutide
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT02461589