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For non-diabetic adults seeking pharmacologic support for weight management, weekly semaglutide achieves markedly superior weight reduction compared with daily liraglutide over 68 weeks, without new safety concerns.
A randomized phase 3b clinical trial comparing two widely used glucagon-like peptide-1 receptor agonists (GLP-1 RAs) shows that once-weekly subcutaneous semaglutide leads to substantially greater and more durable weight loss than once-daily subcutaneous liraglutide in adults with overweight or obesity who do not have diabetes.
The 68-week, open-label study, conducted across 19 sites in the United States, enrolled 338 adults with a body mass index (BMI) of 30 or more, or 27 or more with at least one weight-linked comorbidity. All the volunteers received structured counseling on diet and physical activity alongside pharmacologic treatment. Participants were randomized in a 3:1:3:1 ratio to one of four groups:
Those unable to tolerate the full semaglutide dose could remain on 1.7 mg, while those who could not tolerate liraglutide 3.0 mg discontinued treatment with the option to restart titration. Placebo groups were pooled for analysis (n = 85). The study’s key measure was the percentage difference in body weight between baseline and week 68. Key confirmatory secondary endpoints included the proportion of participants attaining ≥10%, ≥15%, and ≥20% weight loss with semaglutide compared with liraglutide.
Of the 338 randomized volunteers (mean age 49 years; 78.4% women; mean body weight 104.5 kg; mean BMI 37.5), 94.4% completed the trial and 80.2% completed treatment.
(a) Mean weight loss at 68 weeks
(b) Attainment of clinically meaningful weight loss
All comparisons were statistically significant. Treatment discontinuation for any reason occurred less frequently with semaglutide than with liraglutide (13.5% vs 27.6%). Gastrointestinal adverse events were common in both groups and occurred at similar rates (84.1% with semaglutide and 82.7% with liraglutide), consistent with the known safety profiles of GLP-1 RAs.
To sum up, once-weekly semaglutide offers markedly greater weight loss and better treatment persistence than once-daily liraglutide when both are used alongside lifestyle counseling in adults with overweight or obesity without diabetes.
JAMA
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
Domenica Rubino et al.
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