Short answer: in the only head-to-head trial so far, SURMOUNT-5, adults with obesity lost an average of 20.2% of their body weight on tirzepatide (Zepbound), compared with 13.7% on semaglutide (Wegovy), over 72 weeks. Both drugs work, and averages don’t predict what any one person will lose. Which one is right for you is a conversation for your prescriber.
What SURMOUNT-5 compared
- 751 adults with obesity and without type 2 diabetes.
- Each group took the highest dose they could tolerate: up to 15 mg of tirzepatide or 2.4 mg of semaglutide, weekly.
- The trial was open-label, meaning participants knew which drug they were on, and it was funded by Lilly, the maker of tirzepatide.
| Outcome at 72 weeks | Tirzepatide | Semaglutide |
|---|---|---|
| Average weight change | −20.2% | −13.7% |
| Lost at least 10% | 81.6% | 60.5% |
| Lost at least 20% | 48.4% | 27.3% |
| Lost at least 25% | 31.6% | 16.1% |
| Average waist change | −18.4 cm | −13.0 cm |
How they differ
| Semaglutide (Wegovy) | Tirzepatide (Zepbound) | |
|---|---|---|
| How it works | Acts on GLP-1 receptors | Acts on GLP-1 and GIP receptors |
| Dosing | Weekly injection, stepped up from 0.25 mg to 2.4 mg over about 16 weeks. A 7.2 mg dose (Wegovy HD) was approved in 2026, and a daily pill is also available. | Weekly injection starting at 2.5 mg, increased in 2.5 mg steps at least 4 weeks apart, up to 15 mg |
| Common side effects | Nausea, diarrhea, vomiting, constipation, abdominal pain | Nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion |
The comparison above uses semaglutide 2.4 mg. The newer 7.2 mg Wegovy HD dose averaged 18.8% weight loss in its own trial. That’s a different trial with different people, so it can’t be compared directly with SURMOUNT-5. See Wegovy HD 7.2 mg.
Cost
Both manufacturers now sell directly to people paying cash. As of October 2026, Zepbound starts at $299 a month and Wegovy pens are $349 a month. Prices vary by dose and form: see GLP-1 cost without insurance.
Things to ask your prescriber
- Which drug and dose fits your health history and other medications?
- What should you do about side effects while the dose is being increased?
- Does your insurance cover either one, and is a pill an option for you?
Sources
- Aronne et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). NEJM 2025
- Healio: Tirzepatide bests semaglutide for weight loss in adults with obesity
- Weill Cornell Medicine: Head-to-head trial compares weight loss drugs
- Zepbound (tirzepatide) prescribing information
- Wegovy (semaglutide) prescribing information (FDA, 2026)