---
title: "Tirzepatide vs semaglutide: Trial Data Side by Side"
url: https://www.primaralabs.com/research/compare/tirzepatide-vs-semaglutide
source: Primara Labs, markdown mirror of the HTML page
---

# Tirzepatide vs semaglutide

In SURMOUNT-5, a phase 3b trial of tirzepatide in adults with obesity but without type 2 diabetes (n=751), mean body weight fell 20.2% on tirzepatide, maximum tolerated dose over 72 weeks, against 13.7% on semaglutide, maximum tolerated dose (Aronne LJ et al. N Engl J Med 2025 (SURMOUNT-5)). The trials below are set side by side from separate studies, which is not a head-to-head result.

Primara Labs sells some of the compounds covered here. Every figure on this page links to its source and the date it was checked.

Updated 24 September 2026

Mechanism

## How the two differ

### Tirzepatide

Tirzepatide is a single peptide that activates two receptors: GIP (glucose-dependent insulinotropic polypeptide) and GLP-1.

[Source](https://doi.org/10.1056/NEJMoa2206038) · checked 23 September 2026

### Semaglutide

Semaglutide is a GLP-1 analogue that selectively binds to and activates the GLP-1 receptor, the target of native GLP-1.

[Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42bdd912-2393-44c4-b7e0-47672ca28991) · checked 23 September 2026

Head to head

## [SURMOUNT-5](https://www.primaralabs.com/research/trials/surmount-5)

In SURMOUNT-5, a phase 3b trial of tirzepatide in adults with obesity but without type 2 diabetes (n=751), mean body weight fell 20.2% on tirzepatide, maximum tolerated dose over 72 weeks, against 13.7% on semaglutide, maximum tolerated dose (Aronne LJ et al. N Engl J Med 2025 (SURMOUNT-5)).

## Side effects reported

SURMOUNT-5: The abstract does not name the estimand or give adverse event rates.

Cross-trial

## Separate trials, side by side

Choose two to four trials

2 selected.

Mean percent change in body weight by arm, as each source reports it. Navy bars are the trial arms, grey bars the comparator. Bars from different trials are not a head-to-head comparison: populations, durations and estimands differ.

|  | [SURMOUNT-1](https://www.primaralabs.com/research/trials/surmount-1) | [STEP 1](https://www.primaralabs.com/research/trials/step-1) |
| --- | --- | --- |
| Compound | Tirzepatide | Semaglutide |
| Phase | 3 | 3 |
| Population | Adults with BMI of 30 or more, or 27 or more with at least one weight-related complication, excluding diabetes | Adults with BMI of 30 or greater (27 or greater with at least one weight-related coexisting condition), without diabetes |
| n | 2,539 | 1,961 |
| Weeks | 72 | 68 |
| Estimand | treatment-regimen | treatment-policy |
| Arms | 5 mg: -15.0%; 10 mg: -19.5%; 15 mg: -20.9% | 2.4 mg: -14.9% |
| Comparator | Placebo: -3.1% | Placebo: -2.4% |
| Stopped for adverse events | 5 mg: 4.3%; 10 mg: 7.1%; 15 mg: 6.2%; Placebo: 2.6% | Not published in the source read |
| Source | Jastreboff AM et al. N Engl J Med 2022;387:205-216 | Wilding JPH et al. N Engl J Med 2021;384:989-1002 |

SURMOUNT-1: side effects reported

In SURMOUNT-1, discontinuation because of adverse events was 4.3% on 5 mg, 7.1% on 10 mg and 6.2% on 15 mg, against 2.6% on placebo.

STEP 1: side effects reported

STEP 1: Discontinuation for adverse events is not given in the abstract; discontinuation for gastrointestinal adverse events was 4.5% against 0.8% on placebo.

Figures from different trials are not a head-to-head comparison: the populations, durations and estimands differ. The head-to-head trials among these compounds are SURMOUNT-5, tirzepatide against semaglutide, completed, and TRIUMPH-5, retatrutide against tirzepatide, still running.

Questions

## Questions

### Has tirzepatide been compared head to head with semaglutide?

In SURMOUNT-5, a phase 3b trial of tirzepatide in adults with obesity but without type 2 diabetes (n=751), mean body weight fell 20.2% on tirzepatide, maximum tolerated dose over 72 weeks, against 13.7% on semaglutide, maximum tolerated dose (Aronne LJ et al. N Engl J Med 2025 (SURMOUNT-5)).

### Why can the SURMOUNT-1 and STEP 1 figures not be compared directly?

Figures from different trials are not a head-to-head comparison: the populations, durations and estimands differ. The head-to-head trials among these compounds are SURMOUNT-5, tirzepatide against semaglutide, completed, and TRIUMPH-5, retatrutide against tirzepatide, still running. SURMOUNT-1 reports the treatment-regimen estimand over 72 weeks. STEP 1 reports the treatment-policy estimand over 68 weeks.