May 15, 2025 BY
IN Peptide Research

Published in The New England Journal of Medicine on February 10, 2021, this study investigates the efficacy and safety of once-weekly subcutaneous semaglutide (2.4 mg) for weight loss in adults with overweight or obesity but without diabetes. Conducted as a double-blind, randomized, placebo-controlled trial, the study enrolled 1,961 participants with a body mass index (BMI) of 30 or greater (or ≥27 with at least one weight-related coexisting condition). Participants were assigned in a 2:1 ratio to receive semaglutide or placebo, alongside lifestyle interventions, for 68 weeks.

https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

Key Findings:

  • Weight Loss: The semaglutide group experienced a mean body weight reduction of 14.9% from baseline, compared to 2.4% in the placebo group, yielding a significant treatment difference of 12.4 percentage points (95% CI, -13.4 to -11.5; P<0.001).
  • Weight Reduction Goals: A higher proportion of semaglutide-treated participants achieved weight reductions of at least 5%, with many surpassing 10% or 15% loss.
  • Safety Profile: Semaglutide was generally well-tolerated, though gastrointestinal side effects (e.g., nausea, diarrhea) were more common, primarily mild to moderate, and occurred mostly during dose escalation. Serious adverse events were comparable between groups.
  • Additional Benefits: Improvements in cardiometabolic risk factors, such as waist circumference and blood pressure, were observed in the semaglutide group.

The study, part of the global STEP program, highlights semaglutide’s potential as a pharmacologic option for obesity management, addressing a critical gap in effective treatments for this global health challenge. Its findings suggest that semaglutide, previously approved for type 2 diabetes, could play a transformative role in weight management when combined with lifestyle changes.

Links to Related Studies for Further Reading

For those interested in exploring more research on obesity treatments and related pharmacologic interventions, here are additional studies:

  • Tirzepatide as Compared with Semaglutide for the Treatment of Obesity
    New England Journal of Medicine (May 11, 2025)
    This phase 3b trial compares tirzepatide (10 or 15 mg) with semaglutide (1.7 or 2.4 mg) in adults with obesity but without type 2 diabetes, reporting superior weight loss with tirzepatide (-20.2% vs. -13.7% at 72 weeks).
    Read More
  • Dexamethasone and Surgical-Site Infection
    New England Journal of Medicine (May 5, 2021)
    While not directly related to obesity, this study examines dexamethasone’s safety in surgical contexts, relevant for patients with obesity undergoing procedures, finding no increased risk of surgical-site infections with a single 8-mg dose.
    Read More
  • The Physiology of Hunger
    New England Journal of Medicine (January 22, 2025)
    This review explores the physiological mechanisms of hunger, offering insights into feeding behaviors that underpin obesity and potential therapeutic targets.
    Read More

These studies provide a broader context for understanding obesity management, from novel pharmacologic agents to physiological and surgical considerations, enriching the discussion on effective weight loss strategies.

Note: Always consult healthcare professionals before pursuing treatments discussed in these studies. For the full text of the semaglutide study, visit NEJM.org