Semaglutide or tirzepatide: how do they compare?
Written and medically reviewed by Zahraa Sater, M.D., M.P.H.
Reviewed August 12, 2026 · Next review due August 12, 2027
Short answer
Tirzepatide produces more weight loss than semaglutide. In the SURMOUNT-5 head to head trial, adults without diabetes lost 20.2 percent of body weight on tirzepatide and 13.7 percent on semaglutide over 72 weeks. Semaglutide has the stronger cardiovascular outcome evidence, from the SELECT trial. Tolerability, other medical conditions and what you are treating decide the choice, not the average.
Semaglutide and tirzepatide are the two most effective weight medications currently approved, and they are not interchangeable. Tirzepatide activates two receptors, GLP-1 and GIP. Semaglutide activates one. The only direct comparison in adults with obesity and without diabetes, SURMOUNT-5, ran for 72 weeks and found a mean weight reduction of 20.2 percent with tirzepatide and 13.7 percent with semaglutide. That is a real difference, and it is not the only thing that matters.
What the weight loss trials showed
Semaglutide 2.4 mg weekly produced a mean 14.9 percent weight reduction at 68 weeks in STEP 1, against 2.4 percent on placebo. Tirzepatide in SURMOUNT-1 produced 16.0 percent at 5 mg, 21.4 percent at 10 mg and 22.5 percent at 15 mg over 72 weeks in the efficacy analysis, against 2.4 percent on placebo. A higher semaglutide dose, 7.2 mg weekly, was approved as Wegovy HD in March 2026 after the STEP UP trial showed about 18.7 percent weight loss at 72 weeks, with more gastrointestinal side effects than the 2.4 mg dose.
Where semaglutide has the better evidence
Semaglutide is the agent with a completed cardiovascular outcome trial in people who have heart disease and obesity but not diabetes. In SELECT, 17,604 adults were followed for a mean of 40 months and major adverse cardiovascular events fell from 8.0 percent to 6.5 percent, a hazard ratio of 0.80. Semaglutide is also approved for non-cirrhotic MASH with moderate to advanced fibrosis. Tirzepatide holds the approval for moderate to severe obstructive sleep apnoea in adults with obesity, where it reduced the apnoea-hypopnoea index by about 25 to 29 events per hour in SURMOUNT-OSA.
| Semaglutide | Tirzepatide | |
|---|---|---|
| Head to head weight loss, 72 weeks | 13.7 percent | 20.2 percent |
| Stopped for gut side effects in that trial | 5.6 percent | 2.7 percent |
| Cardiovascular outcome trial without diabetes | Yes, SELECT | Not for this population |
| Extra approved indications | MASH with fibrosis | Obstructive sleep apnoea |
| Oral version available | Yes, 25 mg daily tablet | No |
The right question is not which drug is stronger. It is which problem you are treating. If you have established cardiovascular disease, the outcome data point one way. If you have untreated sleep apnoea, they point the other. Ask your prescriber which trial population you most resemble, and agree in advance what response at 12 to 16 weeks would justify staying on the medication.
The clinical detail
SURMOUNT-5 randomised 751 adults with BMI at or above 30, or 27 with a weight-related complication and without diabetes, to maximum tolerated tirzepatide 10 or 15 mg or semaglutide 1.7 or 2.4 mg for 72 weeks. Mean weight change was 20.2 percent versus 13.7 percent, absolute 22.8 kg versus 15.0 kg, with waist circumference falling 18.4 cm versus 13.0 cm (N Engl J Med 2025;393:26-36). In type 2 diabetes the gap narrows and both agents underperform their obesity trials: semaglutide 2.4 mg gave 9.6 percent at 68 weeks in STEP 2, tirzepatide gave 13.4 percent at 10 mg and 15.7 percent at 15 mg at 72 weeks in SURMOUNT-2.
Written and medically reviewed by Zahraa Sater, M.D., M.P.H.
Reviewed August 12, 2026 · Next review due August 12, 2027
Sources
- SURMOUNT-5: Greater Loss of Weight, Waist Circumference With Tirzepatide Than Semaglutide. American College of Cardiology. doi:10.1056/NEJMoa2416394
- STEP 1: Semaglutide Treatment Effect in People With Obesity. American College of Cardiology. PMID 33567185
- SURMOUNT-1 results published in the New England Journal of Medicine. Eli Lilly and Company. PMID 35658024
- SELECT: Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes. American College of Cardiology. PMID 37952131
- ZEPBOUND (tirzepatide) injection, prescribing information, revised January 2026. U.S. Food and Drug Administration
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