“Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial”, 2022-01-11 (; similar):
Question: Among adults with overweight or obesity without diabetes, what is the effect of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg, on weight loss when each is added to counseling for diet and physical activity?
Results: In this randomized clinical trial that included 338 participants, mean body weight change from baseline to 68 weeks was −15.8% with semaglutide vs −6.4% with liraglutide, a statistically-significant difference.
Meaning: 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 statistically-significantly greater weight loss at 68 weeks.
Importance: 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, & 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 & Measures: The 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.
Results: Of 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 < 0.001); weight change with pooled placebo was −1.9%. Participants had statistically-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 < 0.001). 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 & 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 statistically-significantly greater weight loss at 68 weeks.
Trial Registration: ClinicalTrials.gov Identifier: NCT04074161.