Article summary :Title: Tirzepatide Tops Semaglutide for Weight Loss
Article summary :Title: Tirzepatide Tops Semaglutide for Weight Loss
Author: Becky McCall, MSc, MScPH
Published: May 12, 2025
Source: Medscape
Key Summary Points
1. Study Background – SURMOUNT-5 Trial
• First direct head-to-head trial comparing tirzepatide vs semaglutide in patients with obesity but without type 2 diabetes.
• Conducted over 72 weeks, presented at ECO 2025, and published in NEJM.
• Sponsored by Eli Lilly, the maker of tirzepatide (Mounjaro/Zepbound).
2. Participants and Design
• 751 adults (mean BMI: 39.4; mean weight: 113 kg) randomized:
• Tirzepatide group: 10 or 15 mg weekly (n = 374)
• Semaglutide group: 1.7 or 2.4 mg weekly (n = 376)
• Mean age: 44.7 years; 65% women; 76% White
• Median duration of obesity: 16 years
3. Primary Outcomes – Weight Loss
• Tirzepatide: −20.2% weight loss
• Semaglutide: −13.7% weight loss
• P < .001 for superiority of tirzepatide
• Waist circumference reduction: 18.4 cm (tirzepatide) vs 13.0 cm (semaglutide)
4. Proportion Achieving Weight Loss Targets
• ≥10%: 81.6% (tirzepatide) vs 60.5% (semaglutide)
• ≥15%: 64.6% vs 40.1%
• ≥20%: 48.4% vs 27.3%
• ≥25%: 31.6% vs 16.1%
5. Metabolic Improvements (Greater with Tirzepatide)
• Greater reduction in:
• BMI, systolic/diastolic BP, glycemia, insulin, triglycerides, VLDL
• Greater increase in:
• HDL cholesterol
• Similar reductions in LDL and non-HDL cholesterol in both groups
6. Safety Profile
• GI side effects most common; occurred during dose escalation.
• Treatment-emergent AEs: 76.7% (tirzepatide), 79.0% (semaglutide)
• Serious AEs: 3.5% vs 4.8%
• Discontinuation rates: 6.1% vs 8.0%
7. Clinical Implications
• Tirzepatide outperformed semaglutide in both weight loss and metabolic improvements.
• Choice between the two may depend on availability, guidelines, and healthcare system factors.
• Commentators note that tirzepatide’s dual GIP/GLP-1 action likely explains superiority.
