May 15, 2025 BY
IN Peptide Research

Published in The New England Journal of Medicine on May 11, 2025, this phase 3b, open-label, randomized trial compares the efficacy and safety of tirzepatide (10 or 15 mg once weekly) with semaglutide (1.7 or 2.4 mg once weekly) for weight loss in adults with obesity but without type 2 diabetes. Conducted across 47 sites in the United States, the study enrolled 700 participants with a body mass index (BMI) of 30 or greater (or ≥27 with at least one weight-related comorbidity). Participants were assigned in a 1:1 ratio to receive either tirzepatide or semaglutide for 72 weeks, alongside lifestyle interventions.

https://www.nejm.org/doi/full/10.1056/NEJMoa2416394

Key Findings:

  • Weight Loss: The tirzepatide group achieved a mean body weight reduction of 20.2% from baseline, compared to 13.7% in the semaglutide group, with a significant treatment difference of 6.5 percentage points (95% CI, -8.1 to -4.9; P<0.001).
  • Weight Reduction Goals: A greater proportion of tirzepatide-treated participants achieved weight loss of at least 15%, with many surpassing 20% or 25%, compared to semaglutide.
  • Safety Profile: Both drugs were associated with mild to moderate gastrointestinal adverse events (e.g., nausea, vomiting), more frequent with tirzepatide during dose escalation. Serious adverse events were similar between groups, with no new safety concerns identified.
  • Additional Benefits: Tirzepatide showed greater improvements in cardiometabolic markers, including waist circumference and lipid profiles, compared to semaglutide.

This study, part of the SURMOUNT program, underscores tirzepatide’s superior efficacy over semaglutide for obesity management, offering a promising option for patients seeking significant weight loss. The findings build on prior research into GLP-1 receptor agonists, highlighting tirzepatide’s dual GIP and GLP-1 mechanism as a potential advancement in pharmacologic weight management.

Links to Related Studies for Further Reading

For readers interested in diving deeper into obesity treatment and related pharmacologic research, here are additional studies:

  • Once-Weekly Semaglutide in Adults with Overweight or Obesity
    New England Journal of Medicine (February 10, 2021)
    This pivotal trial evaluates semaglutide (2.4 mg weekly) for weight loss, reporting a 14.9% mean weight reduction versus 2.4% with placebo, establishing semaglutide’s role in obesity treatment.
    Read More
  • The Physiology of Hunger
    New England Journal of Medicine (January 22, 2025)
    This review delves into the physiological drivers of hunger, providing insights into appetite regulation and potential therapeutic targets for obesity management.
    Read More
  • Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
    New England Journal of Medicine (June 13, 2019)
    While focused on type 2 diabetes, this study explores oral semaglutide’s cardiovascular safety, relevant for understanding its broader metabolic effects in obesity.
    Read More

These studies offer a comprehensive view of obesity treatment advancements, from comparing novel agents like tirzepatide and semaglutide to understanding the physiological and metabolic underpinnings of weight management.

Note: Consult healthcare providers before considering treatments discussed in these studies. For the full text of the tirzepatide versus semaglutide study, visit NEJM.org.