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Head-to-head · weight loss
Semaglutide vs tirzepatide: the head-to-head numbers
FDA-approved FDA-approved Both drugs. Checked against the trial abstracts Oct 17, 2026
Wegovy or Zepbound? Ozempic or Mounjaro? These two are the biggest names in weight loss, and they've actually gone toe to toe in a randomized trial. Here's who won, by how much, and what the landmark trials showed for each.
SURMOUNT-5: the head-to-head trial
Published in the New England Journal of Medicine in 2025 (Aronne et al., NEJM 2025, PMID 40353578). 751 adults with obesity and without type 2 diabetes were randomized 1:1 to the maximum tolerated weekly dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. It was an open-label phase 3b trial funded by Eli Lilly, the maker of tirzepatide.
| At 72 weeks | Tirzepatide | Semaglutide |
|---|---|---|
| Average weight change | −20.2% | −13.7% |
| Average waist change | −18.4 cm | −13.0 cm |
| Most common side effects | Gastrointestinal in both groups, mostly mild to moderate, mainly during dose escalation | |
The landmark trial for each drug
Each drug also has its own big placebo-controlled trial. These weren't head-to-head, and the people, doses and lengths differ, so compare them loosely.
| Semaglutide: STEP 1 | Tirzepatide: SURMOUNT-1 | |
|---|---|---|
| Source | Wilding et al., NEJM 2021 | Jastreboff et al., NEJM 2022 |
| Who | 1,961 adults with obesity (or overweight plus a weight-related condition), no diabetes | 2,539 adults with obesity (or overweight plus a weight-related complication), no diabetes |
| Length & doses | 68 weeks, 2.4 mg weekly vs placebo, plus lifestyle intervention | 72 weeks, 5, 10 or 15 mg weekly vs placebo |
| Average weight change | −14.9% (−15.3 kg) vs −2.4% on placebo | −15.0% (5 mg), −19.5% (10 mg), −20.9% (15 mg) vs −3.1% on placebo |
| Big-loss club | 50.5% lost 15% or more (vs 4.9% on placebo) | 50% (10 mg) and 57% (15 mg) lost 20% or more (vs 3% on placebo) |
| Stopped for side effects | 4.5% stopped for GI events (vs 0.8% on placebo) | 4.3%, 7.1% and 6.2% stopped for adverse events (vs 2.6% on placebo) |
| Most common side effects | Nausea and diarrhea, typically transient and mild to moderate | Gastrointestinal, mostly mild to moderate, mainly during dose escalation |
How they work
- Semaglutide (Ozempic, Wegovy, Rybelsus) activates one hormone receptor: GLP-1.
- Tirzepatide (Mounjaro, Zepbound) activates two: GIP and GLP-1.
Label dosing for weight management
- Wegovy label: shot steps up from 0.25 mg to a usual 2.4 mg weekly; pill steps up from 1.5 mg to 25 mg daily.
- Zepbound label: starts at 2.5 mg weekly, steps up by 2.5 mg at least every 4 weeks, maintenance 5, 10 or 15 mg.
Copied from the FDA labels on DailyMed via our GLP-1 comparison. Your prescriber sets your dose.
Got a vial and a dose in mg? Our free mg → mL → units calculator shows the math from your own vial label.
Go deeper
- Semaglutide guide: STEP 1, SELECT heart results, label dosing, FAQs.
- Tirzepatide guide: SURMOUNT trials, label dosing, FAQs.
- All four GLP-1s side by side, including retatrutide and orforglipron.
- How to tell if a source is legit.
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Semaglutide vs tirzepatide FAQ
Which is better for weight loss, semaglutide or tirzepatide?
In the only head-to-head trial, SURMOUNT-5, tirzepatide won: −20.2% average weight change at 72 weeks vs −13.7% for semaglutide, in 751 adults with obesity and no type 2 diabetes.
How much weight do people lose on semaglutide?
In STEP 1, adults on semaglutide 2.4 mg weekly averaged −14.9% at 68 weeks (−15.3 kg) vs −2.4% on placebo, alongside lifestyle intervention.
How much weight do people lose on tirzepatide?
In SURMOUNT-1, average weight change at 72 weeks was −15.0% on 5 mg, −19.5% on 10 mg and −20.9% on 15 mg, vs −3.1% on placebo.
What's the difference between how they work?
Semaglutide activates one hormone receptor, GLP-1. Tirzepatide activates two, GIP and GLP-1.
Are the side effects different?
In all three trials the most common side effects were gastrointestinal, mostly mild to moderate and mainly during dose escalation (SURMOUNT) or transient (STEP 1).
What about retatrutide and orforglipron?
See our four-way GLP-1 comparison for all the big names side by side.
Not medical advice. Education only. We don't sell anything or tell you what to take. Label doses are there so you can follow along with your prescriber. Talk to a licensed clinician about your health.