Comparison
Retatrutide vs tirzepatide: how they differ
Tirzepatide acts at two receptors, GIP and GLP-1; retatrutide adds a third, glucagon. Tirzepatide is an approved medicine in the United States, while retatrutide was still investigational when this was written.
How do retatrutide and tirzepatide differ?
Both are synthetic, lipidated peptides that act at incretin hormone receptors and were developed for once-weekly dosing. Tirzepatide is a dual agonist at the GIP and GLP-1 receptors. Retatrutide is a triple agonist that also acts at the glucagon receptor. Their specifications are compared in the table below, rendered from the same records as their product pages.
Which receptors does each one act at?
| Tirzepatide | Retatrutide | |
|---|---|---|
| GLP-1 receptor | Yes | Yes |
| GIP receptor | Yes | Yes |
| Glucagon receptor | No | Yes |
| Development code | LY3298176 | LY3437943 |
The discovery papers explain the designs. Tirzepatide's, in Molecular Metabolism in 2018, describes activity at both incretin receptors. Retatrutide's, in Cell Metabolism in 2022, adds glucagon-receptor activity, which in obese mice was linked to higher energy expenditure.
What have the trials measured?
Tirzepatide's evidence includes the SURPASS programme in type 2 diabetes, for example SURPASS-2 in the New England Journal of Medicine in 2021, which compared it with semaglutide, and the SURMOUNT programme in obesity, including the 72-week SURMOUNT-1 trial in 2022. Retatrutide's evidence includes phase 2 trials published in 2023 and the 80-week phase 3 TRIUMPH-1 trial published in 2026. The cited studies below give each trial's reported figures.
The trials were run separately, in different populations and over different durations, so their figures cannot be compared directly as if from one trial.
Is either one an approved medicine?
Tirzepatide is approved in the United States as Mounjaro, for type 2 diabetes, and as Zepbound, according to the DailyMed labels. No marketing authorisation for retatrutide was found when this was written. Neither status says anything about research-grade material, which is sold here for laboratory use only.
Side by side
| Retatrutide Lyophilised Peptide | Tirzepatide Lyophilised Peptide | |
|---|---|---|
| Form | Lyophilised powder | Lyophilised powder |
| Sizes | 10 mg, 20 mg, 30 mg | 30 mg |
| Price | RM 135–310 | RM 140 |
| Molecular weight | 4,731.4 g/mol | 4,813.5 g/mol |
| CAS number | 2381089-83-2 | 2023788-19-2 |
| Certificate published | Not yet | Not yet |
Cited studies
-
Described in vitro activity at both receptors, effects in mice, and phase 1 pharmacokinetics supporting once-weekly administration.
LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept.. Molecular Metabolism, 2018. doi:10.1016/j.molmet.2018.09.009 · PubMed 30473097
-
Described in vitro receptor activity, effects in obese mice, and a phase 1 single-ascending-dose study with a pharmacokinetic profile supporting once-weekly dosing.
LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.. Cell Metabolism, 2022. doi:10.1016/j.cmet.2022.07.013 · PubMed 35985340
-
In the SURPASS-2 trial, change in HbA1c from baseline was -2.01 to -2.30 percentage points across tirzepatide doses versus -1.86 with semaglutide; gastrointestinal adverse events were most common.
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.. New England Journal of Medicine, 2021. doi:10.1056/NEJMoa2107519 · PubMed 34170647
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In the 72-week SURMOUNT-1 trial, mean body-weight change was -15.0%, -19.5% and -20.9% at 5, 10 and 15 mg versus -3.1% with placebo.
Tirzepatide Once Weekly for the Treatment of Obesity.. New England Journal of Medicine, 2022. doi:10.1056/NEJMoa2206038 · PubMed 35658024
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In a 48-week phase 2 trial in 338 adults, mean body-weight change was -24.2% at 12 mg versus -2.1% with placebo; adverse events were mostly gastrointestinal and dose-related.
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.. New England Journal of Medicine, 2023. doi:10.1056/NEJMoa2301972 · PubMed 37366315
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In the 80-week phase 3 TRIUMPH-1 trial (2,339 adults), mean body-weight change was -25.0% at 12 mg versus -3.9% with placebo; gastrointestinal events were most common.
Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.. New England Journal of Medicine, 2026. doi:10.1056/NEJMoa2604169 · PubMed 42814954
