Short answer: Tirzepatide (Mounjaro, Zepbound) is FDA approved and acts on GIP and GLP-1 receptors. Retatrutide also acts on the glucagon receptor and is not approved; Lilly plans to file with FDA in Q1 2027.1 No trial has compared them head to head. In TRIUMPH-1, retatrutide 12 mg produced 28.3% average weight loss at 80 weeks.2
Because there is no head-to-head trial, the numbers below come from different trials with different people and durations. They are not a direct comparison.
| Retatrutide | Tirzepatide (Mounjaro, Zepbound) | |
|---|---|---|
| Mechanism | GIP, GLP-1 and glucagon receptor agonist (triple agonist)3 | GIP and GLP-1 receptor agonist4 |
| Approval status | Investigational, not FDA approved; BLA planned Q1 20271 | FDA approved (Mounjaro, Zepbound) |
| Dosing schedule | Studied: start 2 mg weekly, stepped up every 4 weeks (2 → 4 → 6 → 9 → 12 mg) to 4, 9 or 12 mg in phase 35 | Label: 2.5 mg weekly for 4 weeks, then up by 2.5 mg at least 4 weeks apart; maintenance 5, 10 or 15 mg4 |
| Half-life | about 6 days (phase 1b)6 | about 5 days7 |
| Time to peak (Tmax) | Not confirmed in a published source | Median 24 hours (8 to 72)4 |
| Dosing frequency | Once weekly in trials | Once weekly |
| Strengths | No approved product; trial doses 1 to 12 mg | Pens or vials 2.5 to 15 mg |
| Weight change in pivotal trial | TRIUMPH-1, 80 weeks: −19.0% (4 mg), −25.9% (9 mg), −28.3% (12 mg) vs −2.2% placebo2 | SURMOUNT-5, 72 weeks: −20.2% at 10 or 15 mg8 |
| Notable warnings | No label yet. In TRIUMPH-1, 11.3% stopped 12 mg for side effects vs 4.9% on placebo2 | Boxed thyroid C-cell tumor warning; pancreatitis, gallbladder, kidney injury, severe GI reactions |
In the phase 2 obesity trial (338 adults, 48 weeks), average weight change was −8.7% on 1 mg, −17.1% on 4 mg, −22.8% on 8 mg and −24.2% on 12 mg, versus −2.1% on placebo. At 24 weeks the 12 mg group was at −17.5%. Doses were stepped up every 4 weeks.3
Two estimands give two numbers for the same trial. The efficacy estimand assumes people stayed on treatment; the treatment-regimen estimand includes people who stopped. Compare like with like.
No. As of October 2026 retatrutide is investigational. Lilly has said it plans to submit a Biologics License Application to FDA in the first quarter of 2027.1 Until then there is no FDA label, approved dosing or approved product.