Clinical comparison · GLP-1 & weight management · Updated 2026-07-02
Semaglutide and tirzepatide are injectable incretin medicines used for weight management and type 2 diabetes. This table reproduces FDA-labeled adverse-event rates and pivotal-trial endpoints verbatim, per cell. The pivotal weight-loss figures come from separate placebo-controlled trials; a direct head-to-head is summarized below.
Every value below is reproduced verbatim from an FDA prescribing-information document or a published clinical trial, and each cell links to its source. This page does not rank the two options, does not declare one safer or more effective, and is not medical advice.
| Dimension | Semaglutide | Tirzepatide |
|---|---|---|
| Drug class | GLP-1 receptor agonist[1] | Dual GIP and GLP-1 receptor agonist[2] |
| Route | Once-weekly subcutaneous injection[1] | Once-weekly subcutaneous injection[2] |
| Highest maintenance dose (weight management) | 2.4 mg once weekly (Wegovy)[3] | 15 mg once weekly (Zepbound/Mounjaro)[2] |
| Pivotal mean body-weight change | -14.9% at week 68 vs -2.4% placebo (STEP 1)[4] | -20.9% at week 72 vs -3.1% placebo (SURMOUNT-1, 15 mg)[5] |
| Nausea (common adverse event) | 15-20%[1] | 12-18%[2] |
| Diarrhea | 8-9%[1] | 12-17%[2] |
| Vomiting | 5-9%[1] | 5-13%[2] |
| Boxed warning | Thyroid C-cell tumors; contraindicated in personal/family history of MTC or MEN 2[1] | Thyroid C-cell tumors; contraindicated in personal/family history of MTC or MEN 2[2] |
| Pregnancy | Not recommended; discontinue >=2 months before a planned pregnancy[3] | Not recommended; discontinue >=2 months before a planned pregnancy[2] |
Direct head-to-head (SURMOUNT-5)
SURMOUNT-5 compared the two medicines directly in adults with obesity. It reported a mean body-weight change of -20.2% with tirzepatide versus -13.7% with semaglutide at 72 weeks. See the registry entry for full details. SURMOUNT-5 (NCT05822830)
Why STEP 1 and SURMOUNT-1 are not a head-to-head
The -14.9% and -20.9% figures are from separate placebo-controlled trials (STEP 1 and SURMOUNT-1) with different populations and durations. They should be read as each drug versus placebo, not against each other. SURMOUNT-1 (NEJM 2022)
The SURMOUNT-5 head-to-head reported a mean body-weight change of -20.2% with tirzepatide versus -13.7% with semaglutide at 72 weeks in adults with obesity (NCT05822830).
Yes. Both FDA labels carry a boxed warning for thyroid C-cell tumors and are contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2.
STEP 1 reported -14.9% mean body-weight change for semaglutide at week 68; SURMOUNT-1 reported -20.9% for tirzepatide 15 mg at week 72. These are separate trials, not a head-to-head.
Editorial reviews from ClearHormones of telehealth providers in this category. These are not treatment recommendations, and prescribing decisions rest with a licensed clinician.