---
title: "How Does Tirzepatide Work? GIP and GLP-1 Explained"
url: https://www.primaralabs.com/answers/how-does-tirzepatide-work
source: Primara Labs, markdown mirror of the HTML page
---

# How does tirzepatide work?

Tirzepatide is one peptide that activates two incretin receptors, GIP and GLP-1, which is why it is called a dual agonist. As of 23 September 2026 it is the active ingredient in US-approved prescription medicines, and its SURMOUNT phase 3 trials measured body-weight change in adults with obesity, with and without type 2 diabetes.

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 23 September 2026

01

## Two receptors in one molecule

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

Semaglutide activates GLP-1 alone, and retatrutide adds the glucagon receptor to these two. GIP and GLP-1 are both released by the gut after a meal, and both act on insulin release and appetite signalling.

02

## What SURMOUNT measured

In SURMOUNT-1, a phase 3 trial of tirzepatide in adults with BMI of 30 or more, or 27 or more with at least one weight-related complication, excluding diabetes (n=2,539), mean body weight fell 15.0% on 5 mg, 19.5% on 10 mg and 20.9% on 15 mg over 72 weeks, against 3.1% on placebo (treatment-regimen estimand; Jastreboff AM et al. N Engl J Med 2022;387:205-216).

In SURMOUNT-5, a phase 3b head-to-head trial in adults with obesity but without type 2 diabetes (n=751), mean body weight fell 20.2% on tirzepatide against 13.7% on semaglutide over 72 weeks.

03

## Adverse events

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.

04

## With type 2 diabetes

In SURMOUNT-2, a phase 3 trial in adults (18 or older) with BMI of 27 kg/m2 or higher and type 2 diabetes with HbA1c 7-10% (53-86 mmol/mol), in seven countries (n=938), mean body weight fell 14.7% on the 15 mg arm over 72 weeks, against 3.2% lost on placebo (treatment-regimen estimand).

The estimand in brackets says which question a figure answers: an efficacy estimand counts people while they stayed on treatment, and a treatment-regimen or treatment-policy estimand counts everyone randomised, whatever happened later, so it usually reads lower.

Sources

## Where every figure comes from

1.  [Tirzepatide mechanism source](https://doi.org/10.1056/NEJMoa2206038) · checked 23 September 2026
2.  [Jastreboff AM et al. N Engl J Med 2022;387:205-216](https://doi.org/10.1056/NEJMoa2206038) · checked 23 September 2026
3.  [Aronne LJ et al. N Engl J Med 2025 (SURMOUNT-5)](https://doi.org/10.1056/NEJMoa2416394) · checked 23 September 2026

Last reviewed 23 September 2026

Read next

## Related pages

-   [Tirzepatide 15mg](https://www.primaralabs.com/marketplace/tirzepatide-15mg)
-   [SURMOUNT-1 on the Trial Explorer](https://www.primaralabs.com/research/trials/surmount-1)
-   [Tirzepatide vs semaglutide: trial data](https://www.primaralabs.com/research/compare/tirzepatide-vs-semaglutide)

-   [What are the side effects of tirzepatide?](https://www.primaralabs.com/answers/what-are-the-side-effects-of-tirzepatide)
-   [Is tirzepatide approved in the Philippines?](https://www.primaralabs.com/answers/is-tirzepatide-approved-in-the-philippines)