BACKGROUND AND PURPOSE:

• Semaglutide is an approved treatment for type 2 diabetes and reduces the risk of cardiovascular events in this population
• Wilding et al. (NEJM, 2021) examined whether adults with obesity can achieve weight loss with this medication, along with lifestyle intervention

METHODS:

• Randomized, double-blind, placebo-controlled trial
• Participants
  • BMI ≥30 or ≥27 (in addition to ≥1 weight-related coexisting condition)
  • Non-diabetic
• Interventions (randomized 2:1)
  • Semaglutide and lifestyle intervention | 68 weeks of treatment with once-weekly subcutaneous semaglutide 2.4 mg
  • Placebo and lifestyle intervention
• Primary outcomes
  • Percentage change in body weight
  • Weight reduction of at least 5%

RESULTS:

• 1306 participants in semaglutide | 655 participants in placebo
• Participants in the semaglutide group experienced a significantly greater change in body weight from baseline to week 68 (P < 0.001)
  • Semaglutide: −14.9%
  • Placebo: −2.4%
  • Estimated treatment difference: −12.4 percentage points (95% CI, −13.4 to −11.5)
• More participants in the semaglutide group achieved weight reduction at 68 weeks
  • 5% or more
    • Semaglutide: 86.4%
    • Placebo: 31.5%
  • 10% or more
    • Semaglutide: 69.1%
    • Placebo: 12.0%
  • 15% or more
    • Semaglutide: 50.5%
    • Placebo: 4.9%
  • P <0.001 for all three comparisons of odds
• Change in body weight from baseline to week 68
  • Semaglutide: −15.3 kg
  • Placebo: −2.6 kg
  • Estimated treatment difference: −12.7 kg (95% CI, −13.7 to −11.7)
• Participants who received semaglutide had
  • Greater improvement with respect to cardiometabolic risk factors
  • Greater increase in participant-reported physical functioning from baseline
• Side effects of Semaglutide
  • Primarily nausea and diarrhea
  • Typically transient and mild-to-moderate in severity and subsided with time
  • More participants in the semaglutide group discontinued treatment owing to GI events vs placebo (4.5% vs 0.8%)

CONCLUSION:

• Semaglutide plus lifestyle interventions resulted in sustained weight loss in non-diabetic individuals
•  The authors conclude

…that among adults with overweight or obesity (without diabetes), once-weekly subcutaneous semaglutide plus lifestyle intervention was associated with substantial, sustained, clinically relevant mean weight loss of 14.9%, with 86% of participants attaining at least 5% weight loss 

Learn More – Primary Sources:

Once-Weekly Semaglutide in Adults with Overweight or Obesity

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