Tirzepatide vs retatrutide
Tirzepatide is an approved drug that acts on two hormone receptors. Retatrutide, also from Eli Lilly, adds a third, glucagon, and is still in trials. A head-to-head trial is under way.
- Tirzepatide
- Approved drugOnce weekly
- Retatrutide
- Human studiesOnce weekly
- Head-to-head trials
- None published
The short answer
Tirzepatide (Zepbound, Mounjaro) activates the GIP and GLP-1 receptors. Retatrutide activates those two plus the glucagon receptor. Both are once-weekly injections from Eli Lilly, stepped up every 4 weeks.
Retatrutide’s trial numbers are bigger: 25.0% weight loss at 80 weeks on 12 mg in TRIUMPH-1, counting everyone who started, vs 20.9% at 72 weeks on tirzepatide 15 mg in SURMOUNT-1. Those come from separate trials with different lengths and people, so they can’t be ranked. TRIUMPH-5, about 800 adults with obesity randomized to one or the other for 80 weeks, is built to settle it; the registry lists its primary completion as November 2026. Retatrutide isn’t approved, and Lilly plans to file with FDA in early 2027.
At a glance
| Field | TirzepatideActive ingredient in Mounjaro and Zepbound | RetatrutideLY3437943 |
|---|---|---|
| Evidence | Approved drug | Human studies |
| Class | Dual GIP / GLP-1 receptor agonist | GIP / GLP-1 / glucagon triple agonist |
| Approval | Approved in the US as Mounjaro (type 2 diabetes, including heart-risk reduction) and Zepbound (weight management and obstructive sleep apnea). | Not approved anywhere; in Phase 3 trials. Lilly said in July 2026 it plans to file with FDA in the first quarter of 2027. |
| Sport (WADA 2026) | Not banned in sport | Likely banned in sport |
| Common dose | 2.5 → 15 mg weekly | 2 → 12 mg weekly |
| Frequency | Once weekly | Once weekly |
| Cycle | Continuous | Continuous |
| Route | Subcutaneous injection | Subcutaneous injection |
| Half-life | about 5 to 6 days Label | about 6 days Trial |
| Typical draw | 10 units50 mg with 2 mL, 2.5 mg | 10 units40 mg with 2 mL, 2 mg |
| Vial sizes or form | 5, 10, 20, 30, 40, 50, 60, 100 mg | 5, 10, 20, 30, 40, 50, 60 mg |
| Human studies | 5 listedLargest: 13,299 people (2025) | 5 listedLargest: 2,339 people (2026) |
| Main cautions |
|
|
| Open Tirzepatide | Open Retatrutide |
Doses shown are what labels, trials or community reports reference, not recommendations. Each compound’s page has the full detail and sources.
Key differences
How they work
Tirzepatide: GIP and GLP-1 receptors. Retatrutide: GIP, GLP-1 and glucagon receptors.
Approval
Tirzepatide is approved in the US for weight management, sleep apnea and type 2 diabetes. Retatrutide isn’t approved anywhere; Lilly said in July 2026 it plans to file with FDA in the first quarter of 2027.
Weight loss in trials
TrialTirzepatide 5, 10 and 15 mg: 15.0%, 19.5% and 20.9% at 72 weeks vs 3.1% on placebo (SURMOUNT-1). Retatrutide 4, 9 and 12 mg: 17.6%, 23.7% and 25.0% at 80 weeks vs 3.9% (TRIUMPH-1), or 28.3% on 12 mg among people who stayed on treatment.
Doses
Tirzepatide starts at 2.5 mg and rises 2.5 mg every 4 weeks to 5, 10 or 15 mg (label). Retatrutide’s Phase 3 trials started at 2 mg and stepped up every 4 weeks to 4, 9 or 12 mg.
Side effects
TrialBoth cause nausea, diarrhea, vomiting and constipation that rise with dose. Retatrutide’s trials add a faster heart rate and skin sensitivity (dysesthesia, about 12% at 9–12 mg vs 1% on placebo); at 12 mg, 11.3% stopped because of side effects vs 4.9% on placebo.
In sport
Tirzepatide isn’t banned; WADA tracks it in its Monitoring Program. Retatrutide falls under WADA’s S0 rule for drugs with no approval anywhere, so it is likely banned at all times.
Head-to-head studies
Taking them together
Tirzepatide and retatrutide both act on the GLP-1 receptor. The Wegovy and Zepbound labels say not to combine them with any other GLP-1 receptor agonist.
Source: Wegovy and Zepbound prescribing information, section 1
Open them in the stack check for sport status and one combined tracking checklist.
Questions
What is the difference between tirzepatide and retatrutide?
Tirzepatide (Zepbound, Mounjaro) activates the GIP and GLP-1 receptors. Retatrutide activates those two plus the glucagon receptor. Both are once-weekly injections from Eli Lilly, stepped up every 4 weeks.
Is retatrutide stronger than tirzepatide?
Its trials report bigger weight losses (25.0% at 80 weeks on 12 mg vs 20.9% at 72 weeks on tirzepatide 15 mg), but those come from separate trials. The head-to-head trial, TRIUMPH-5, hasn’t reported. Retatrutide also isn’t approved, and its long-term safety is still being studied.
Can tirzepatide and retatrutide be taken together?
The stack check flags two GLP-1 drugs. Tirzepatide and retatrutide both act on the GLP-1 receptor. The Wegovy and Zepbound labels say not to combine them with any other GLP-1 receptor agonist. No published study has tested them together.
Which has more evidence in people, tirzepatide or retatrutide?
Tirzepatide is approved in the US; its page lists 5 key human studies. Retatrutide is in clinical trials and not approved; its page lists 5 key human studies. They haven’t been compared directly in a published trial.
Are tirzepatide and retatrutide banned in sport?
Retatrutide is likely banned under WADA’s S0 rule for unapproved drugs. Tirzepatide isn’t banned. This follows the WADA 2026 Prohibited List; athletes should confirm with their anti-doping organization.
Sources
- TRIUMPH-5, retatrutide compared with tirzepatide in adults with obesity: ClinicalTrials.gov registry entry, updated July 2026 NCT06662383
- Jastreboff et al., retatrutide for obesity, TRIUMPH-1 (NEJM 2026) PMID 42814954
- Jastreboff et al., tirzepatide for obesity, SURMOUNT-1 (NEJM 2022) PMID 35658024
- Zepbound prescribing information, rev. 08/2026 (Eli Lilly)
Each compound’s page lists its full sources: Tirzepatide, Retatrutide.