SURMOUNT-5: Tirzepatide vs Semaglutide Head-to-Head (2025 Evidence)
What the 2025 SURMOUNT-5 head-to-head trial showed about tirzepatide versus semaglutide for weight loss, and what it means for telehealth patients comparing GLP-1 options.
Is tirzepatide more effective than semaglutide for weight loss?
In SURMOUNT-5, the first large head-to-head trial (published in the New England Journal of Medicine in 2025), tirzepatide produced greater average weight loss than semaglutide — about 20.2% versus 13.7% over 72 weeks in adults with obesity and without diabetes. Tirzepatide also led to larger waist-circumference reductions. Both are effective; the right choice is clinical and individual.
Disclaimer: American Telehealth Review is an editorial resource and does not provide medical advice, diagnosis, or treatment. Compounded medications are not FDA-approved finished drug products and should only be prescribed when clinically appropriate by a licensed healthcare provider. Brand-name medications such as Ozempic, Wegovy, Mounjaro, and Zepbound are FDA-approved under their own applications. Compounded semaglutide and compounded tirzepatide are not FDA-approved finished drug products.
What the trial found
SURMOUNT-5 randomized adults with obesity or overweight with comorbidities to tirzepatide or semaglutide 2.4 mg. At 72 weeks, the tirzepatide group lost more weight on average, and a higher share reached ≥15%, ≥20%, and ≥25% loss thresholds. Gastrointestinal side effects were common in both groups during dose escalation.
What it means for patients
Greater average efficacy does not make tirzepatide right for everyone — cost, tolerability, dosing, and eligibility matter. Compounded versions of both are accessed via telehealth and are not FDA-approved finished products. For an independent monthly-cost view, see the GLP-1 price index.
Mean weight loss in pivotal GLP-1 trials
| Medication | Trial (year) | Mean weight loss |
|---|---|---|
| Tirzepatide 15 mg | SURMOUNT-1 (2022) | 20.9% |
| Tirzepatide | SURMOUNT-5 (2025) | 20.2% |
| Semaglutide 2.4 mg | STEP 1 (2021) | 14.9% |
| Semaglutide 2.4 mg | SURMOUNT-5 (2025) | 13.7% |
| Oral semaglutide 25 mg | OASIS-4 (2025) | 13.6% |
| Oral orforglipron 36 mg | ATTAIN-1 (2025) | 12.4% |
Data shown in the chart above. Compounded versions are not the FDA-approved products studied in these trials.
Frequently asked questions
Did SURMOUNT-5 show tirzepatide beats semaglutide?
Yes, on average weight loss (about 20.2% vs 13.7% at 72 weeks), but individual results and tolerability vary.
Are compounded versions the same as the trial drugs?
No. Trials used the FDA-approved branded products; compounded semaglutide and tirzepatide are not FDA-approved finished drug products.
Sources
- Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med. 2025.
- Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022.
- U.S. FDA — Medications containing semaglutide and tirzepatide; Compounding and the FDA (fda.gov).