Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes
Authors: Domenica M. Rubino, Frank L. Greenway, Usman Khalid, Patrick M. O’Neil, Julio Rosenstock, Rasmus Sørrig, Thomas A. Wadden, Alicja Wizert, W. Timothy Garvey, Carlos Arauz-Pacheco, Kevin Cannon, H. Jackson Downey, David Fitz-Patrick, Jeffrey Geohas, Gregg Gerety, John Gilbert, Priscilla Hollander, Eric Klein, Karen Laufer, Philip O'Donnell, Paul Rosenblit, Phillip Toth
Journal: JAMA (2022)

InvestigatorsIMPORTANCE Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management.OBJECTIVE To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity.DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without diabetes (N = 338).INTERVENTIONS Participants were randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity.Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the 4-week titration.Placebo groups were pooled (n = 85). MAIN OUTCOMES AND MEASURESThe primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68.Semaglutide vs liraglutide comparisons were open-label, with active treatment groups double-blinded against matched placebo groups.Comparisons of active treatments vs pooled placebo were supportive secondary end points. RESULTSOf 338 randomized participants (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean [SD] body weight, 104.5 [23.8] kg; mean [SD] body mass index, 37.5 [6.8]), 319 (94.4%) completed the trial, and 271 (80.2%) completed treatment.The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide (difference, -9.4 percentage points [95% CI, -12.0 to -6.8]; P < .001);weight change with pooled placebo was -1.9%.Participants had significantly greater odds of achieving 10% or more, 15% or more, and 20% or more weight loss with semaglutide vs liraglutide (70.9% of participants vs 25.6% [odds ratio, 6.3 {95% CI, 3.5 to 11.2}], 55.6% vs 12.0% [odds ratio, 7.9 {95% CI, 4.1 to 15.4}], and 38.5% vs 6.0% [odds ratio, 8.2 {95% CI, 3.5 to 19.1}], respectively; all P < .001).Proportions of participants discontinuing treatment for any reason were 13.5% with semaglutide and 27.6% with liraglutide.Gastrointestinal adverse events were reported by 84.1% with semaglutide and 82.7% with liraglutide.CONCLUSIONS AND RELEVANCE Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks.