Evidence review
What the 2025 SURMOUNT-5 head-to-head trial showed about tirzepatide versus semaglutide for weight loss, and what it means for telehealth patients.
Published June 1, 2026 · GLP1 One Telehealth Editorial Team
In SURMOUNT-5 (New England Journal of Medicine, 2025), the first large head-to-head trial, tirzepatide produced greater average weight loss than semaglutide — about 20.2% versus 13.7% over 72 weeks in adults with obesity. Both are effective; the right choice is individual and clinical.
Educational use only. This article is for educational purposes only and does not provide medical advice. Compounded semaglutide and compounded tirzepatide are not FDA-approved finished drug products and should only be prescribed when clinically appropriate by a licensed healthcare provider.
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% |
Compounded versions are not the FDA-approved products studied in these trials.
SURMOUNT-5 randomized adults with obesity to tirzepatide or semaglutide 2.4 mg. At 72 weeks the tirzepatide group lost more on average and more often reached the ≥15%, ≥20%, and ≥25% thresholds. Gastrointestinal side effects were common in both during dose escalation.
Greater average efficacy doesn't make tirzepatide right for everyone — tolerability, cost, dosing, and eligibility matter. Compounded versions are not the FDA-approved products studied. Compare cost via the GLP-1 price comparison guide.
On average weight loss, yes (about 20.2% vs 13.7% at 72 weeks); individual results vary.
No; the trials used FDA-approved branded products, not compounded medications.