Once-Weekly Semaglutide in Adults with Overweight or Obesity.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 33567185 · doi:10.1056/NEJMoa2032183
What was done
In a double-blind trial, 1961 adults without diabetes with a BMI of 30 or greater (or 27 or greater with at least one weight-related condition) were randomized 2:1 to 68 weeks of once-weekly subcutaneous semaglutide (2.4 mg) or placebo, both alongside lifestyle intervention. The coprimary endpoints were percentage change in body weight and the proportion of participants achieving at least a 5% reduction in body weight at week 68.
What was found
Mean weight change at week 68 was -14.9% (-15.3 kg) with semaglutide versus -2.4% (-2.6 kg) with placebo (treatment difference: -12.4 percentage points [95% CI, -13.4 to -11.5; P<0.001] and -12.7 kg [95% CI, -13.7 to -11.7]). Weight loss thresholds were met more frequently with semaglutide than placebo: >=5% weight loss was achieved by 86.4% (1047 participants) vs 31.5% (182 participants), >=10% by 69.1% (838) vs 12.0% (69), and >=15% by 50.5% (612) vs 4.9% (28) (P<0.001 for all). Gastrointestinal adverse events (nausea, diarrhea) were the most common side effects; treatment discontinuation due to gastrointestinal events occurred in 4.5% (59 participants) on semaglutide versus 0.8% (5 participants) on placebo.
Why it matters
Once-weekly semaglutide at 2.4 mg provides clinically meaningful, high-magnitude weight reduction and cardiometabolic improvements over 68 weeks as an adjunct to lifestyle intervention.
Limits
Adults with diabetes were excluded, limiting generalizability to that group. The trial was funded by the manufacturer (Novo Nordisk), assessed outcomes only up to 68 weeks without reporting post-treatment weight maintenance in the abstract, and semaglutide caused higher rates of gastrointestinal adverse events leading to discontinuation.
Cited by
- contradicts Participants adhering to lifestyle and behavioral weight management programs achieved superior results compared to those using weight-loss medications alone.