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

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.

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.

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.

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

Tirzepatide mechanism source · checked 23 September 2026
Jastreboff AM et al. N Engl J Med 2022;387:205-216 · checked 23 September 2026
Aronne LJ et al. N Engl J Med 2025 (SURMOUNT-5) · checked 23 September 2026

Last reviewed 23 September 2026