The landscape of weight management medications has evolved, presenting clinicians and patients with more options than ever before. Among these, glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide and liraglutide have emerged as effective treatments for obesity. Despite both being available for weight management, direct comparisons from phase 3 trials were lacking. This study addresses this gap by directly comparing the efficacy and safety profiles of once-weekly subcutaneous semaglutide 2.4 mg versus once-daily subcutaneous liraglutide 3.0 mg in individuals with overweight or obesity.
This 68-week, phase 3b, randomized, open-label trial enrolled 338 adults with a body mass index (BMI) of 30 or greater, or 27 or greater with at least one weight-related comorbidity, excluding those with diabetes. Participants were randomly assigned to receive either once-weekly semaglutide 2.4 mg, once-daily liraglutide 3.0 mg, or placebo, alongside diet and physical activity counseling. The primary endpoint was the percentage change in body weight at week 68, with secondary endpoints including achieving weight loss of 10%, 15%, and 20% or more.
The results demonstrated a significant difference in weight loss between the two active treatments. Participants treated with semaglutide experienced a mean weight loss of -15.8% from baseline, compared to -6.4% with liraglutide. This translates to a notable difference of -9.4 percentage points (95% CI, -12.0 to -6.8; P < .001), highlighting a considerably greater weight reduction with semaglutide. When we look at these percentages roughly, the weight loss with semaglutide is almost in the range of 5 to 8 while with liraglutide it’s closer to 5 to 3 in terms of simplified ratios, showcasing a clear advantage for semaglutide.
Furthermore, semaglutide was significantly more effective in helping patients achieve clinically meaningful weight loss thresholds. A striking 70.9% of participants on semaglutide achieved 10% or more weight loss, compared to only 25.6% on liraglutide (odds ratio, 6.3 [95% CI, 3.5 to 11.2]). Even more pronounced differences were observed for higher weight loss targets: 55.6% vs 12.0% for 15% or more weight loss (odds ratio, 7.9 [95% CI, 4.1 to 15.4]), and 38.5% vs 6.0% for 20% or more weight loss (odds ratio, 8.2 [95% CI, 3.5 to 19.1]), all with P < .001.
While both medications had similar rates of gastrointestinal adverse events (84.1% with semaglutide and 82.7% with liraglutide), a notable difference was seen in treatment discontinuation rates. The proportion of participants discontinuing treatment for any reason was lower with semaglutide (13.5%) compared to liraglutide (27.6%).
In conclusion, this direct comparison trial provides robust evidence that in adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide 2.4 mg is significantly more effective for weight loss than once-daily subcutaneous liraglutide 3.0 mg when combined with diet and physical activity counseling. The magnitude of weight loss achieved with semaglutide, reflected in the approximate 5 8 Compared To 5 3 weight loss ratio against liraglutide, along with higher rates of achieving significant weight loss thresholds, underscores its potential as a superior treatment option for individuals seeking substantial weight reduction.
