New SURMOUNT-5 Trial Results (2025)
Key Takeaways
✅ Tirzepatide (Zepbound) led to significantly greater weight loss than semaglutide (Wegovy).
- Average weight loss: –20.2% with tirzepatide vs. –13.7% with semaglutide at 72 weeks.
✅ More patients on tirzepatide achieved major weight-loss milestones (15%, 20%, or even 25% body weight loss).
✅ Waist circumference shrank more with tirzepatide (–18.4 cm vs. –13.0 cm).
✅ Both drugs had similar side effects (mostly mild-to-moderate nausea, vomiting, and diarrhea).
Background: The Rise of GLP-1 Drugs for Obesity
Obesity is a chronic disease linked to heart disease, diabetes, and early death. For years, lifestyle changes alone weren’t enough for many people to achieve lasting weight loss.
Then came GLP-1 receptor agonists:
- Semaglutide (Wegovy) – Approved in 2021, averages ~15% weight loss.
- Tirzepatide (Zepbound) – Approved in 2023, combines GLP-1 + GIP hormones, averages ~20% weight loss in earlier trials.
But until now, no head-to-head trial had compared them directly in people without diabetes.
The SURMOUNT-5 Trial: Study Design
- Participants: 751 adults with obesity (BMI ≥30 or ≥27 with weight-related conditions) without type 2 diabetes.
- Treatment:
- Tirzepatide group: 10 mg or 15 mg weekly (max tolerated dose).
- Semaglutide group: 1.7 mg or 2.4 mg weekly (max tolerated dose).
- Duration: 72 weeks (~1.5 years).
- Primary Goal: Percent weight loss from baseline.
Results: Tirzepatide Wins on Weight Loss & Waist Reduction
1. Weight Loss Comparison
2. Waist Circumference (Belly Fat) Reduction
- Tirzepatide: –18.4 cm (~7.2 inches)
- Semaglutide: –13.0 cm (~5.1 inches)
- Difference: Tirzepatide reduced waist size by 5.4 cm (~2.1 inches) more (P<0.001).
Safety & Side Effects: Both Drugs Similar
Both medications had mostly mild-to-moderate GI side effects:
- Nausea (~30-40%)
- Diarrhea (~20-25%)
- Vomiting (~10-15%)
- No major safety differences between groups.
Key Note: Side effects usually occurred during dose escalation and improved over time.
Why Is Tirzepatide More Effective?
Tirzepatide has a dual hormone action:
- GLP-1 – Slows digestion, reduces appetite.
- GIP – May enhance fat-burning and insulin sensitivity.
Semaglutide only targets GLP-1, which might explain why tirzepatide leads to greater weight loss.
What This Means for Patients
- If you need maximum weight loss: Tirzepatide (Zepbound) is more effective than semaglutide (Wegovy).
- If cost/access is an issue: Semaglutide still provides meaningful weight loss (~13-15%).
- Side effects are similar, so personal tolerance may guide choice.
Future Questions
- Will tirzepatide keep weight off longer-term (beyond 72 weeks)?
- Could even higher doses (e.g., tirzepatide 15 mg) lead to >25% weight loss?
Bottom Line
Tirzepatide is the new leader in obesity pharmacotherapy, offering ~20% weight loss—significantly more than semaglutide. However, both drugs are safe and effective options for people struggling with obesity.
Interested in trying these medications? Consult your doctor to discuss which one fits your health profile and goals.
