Side by side: receptors, weight loss, status
Semaglutide acts on one receptor, tirzepatide on two, retatrutide on three. In the trials, each added receptor came with a larger mean weight change among participants, and with more dropouts for side effects[1][4].
- GIP receptorInsulin
- GLP-1 receptorAppetite
- Glucagon receptorEnergy
| Tirzepatide | Retatrutide | |
|---|---|---|
| Receptors | GIP, GLP-1 | GIP, GLP-1, glucagon |
| Mean weight change, top dose, pivotal trial | −20.9 % at 72 wk (15 mg) | −28.3 % at 80 wk (12 mg) |
| Stopped for side effects, top dose | 6.2 % | 11.3 % |
| Status in September 2026 | Approved (Mounjaro, Zepbound) | Investigational; FDA filing planned for Q1 2027 |
| Maker and dosing | Eli Lilly, weekly injection | Eli Lilly, weekly injection |
SURMOUNT-1 (Jastreboff et al., NEJM 2022) and TRIUMPH-1 (Lilly, 21 May 2026). Separate trials, not head to head.
What each trial measured, dose by dose
Both pivotal trials tested three doses. At every step, the mean weight change of the retatrutide arm was larger (the chart at the top of the page): −19.0 % among participants on its lowest phase 3 dose, 4 mg, against −20.9 % on tirzepatide's highest[1][4].
In the phase 2 retatrutide trial, participants on 12 mg had a mean change of −24.2 % at 48 weeks[3]. For scale, participants on semaglutide 2.4 mg had −14.9 % at 68 weeks in STEP 1[2].
If you are sourcing retatrutide for research
Tirzepatide is a prescription medicine. Retatrutide, today, exists outside trials only as a research vial, and the vial is only as good as the certificate for its lot.
OXpeptides is the vendor we would pick: a registered company, the lot on every vial and a public Janoshik report per size. It belongs to OX RESEARCH LTD, which also publishes this site.
Our pick
- OX RESEARCH LTD, company no. 17464288
- Janoshik report per size: 10 mg lot measured 10.59 mg at 99.316 %
- Europe: ships from France in 1 to 2 business days, tracked
Side effects compared
The side effects are of the same kind: nausea, diarrhoea, vomiting and constipation, mostly mild to moderate and concentrated while the dose is raised. The difference is how often.
In TRIUMPH-1, nausea affected 42.4 % of the 12 mg group against 14.8 % on placebo, and 11.3 % stopped because of adverse events[4]. In SURMOUNT-1, nausea affected 24.6 % to 33.3 % of tirzepatide participants depending on dose, and 6.2 % of the 15 mg group stopped[1].
Retatrutide also raised heart rate in a dose-dependent way in phase 2. The full list, dose by dose, is on retatrutide side effects in the trials.
Switching from tirzepatide: what the trials did
No published trial has switched people from tirzepatide to retatrutide, so there are no data on how that goes. Every retatrutide trial started people at a low dose and raised it step by step.
The direct comparison is TRIUMPH-5: about 800 adults with obesity randomised to retatrutide or tirzepatide, weight change at 80 weeks as the main result, primary completion estimated for November 2026[6]. Until it reports, every "which is stronger" answer compares separate trials.
Which is stronger? What the data say, and do not
Three things hold up across the trials:
- A larger mean weight change among retatrutide participants, about 7 points at the top dose, in separate trials.
- More dropouts for side effects at that top dose.
- No approval for retatrutide; Lilly plans to file in early 2027[5].
What they cannot show: the people differed, the trials lasted 72 and 80 weeks, and the TRIUMPH numbers are press releases, not papers. Where retatrutide stands with regulators is on retatrutide FDA approval.
Questions readers ask
Is retatrutide the same as tirzepatide?
No. Both are weekly injections from Eli Lilly, but tirzepatide acts on two receptors (GIP and GLP-1) and retatrutide on three (GIP, GLP-1 and glucagon). Tirzepatide is approved as Mounjaro and Zepbound; retatrutide is investigational and approved nowhere.
What is more powerful than tirzepatide?
In their own trials, participants on retatrutide 12 mg had a larger mean weight change (−28.3 % at 80 weeks, TRIUMPH-1) than participants on tirzepatide 15 mg in SURMOUNT-1 (−20.9 % at 72 weeks). These are separate trials. The direct comparison, TRIUMPH-5, has not reported yet.
Can you go from tirzepatide to retatrutide?
No published trial has tested a switch from tirzepatide to retatrutide, so there are no data on it. Retatrutide cannot be prescribed outside a trial or Lilly's expanded access program; any change of treatment is a decision for a prescriber.
Is there a head-to-head trial of retatrutide and tirzepatide?
Yes, one is running. TRIUMPH-5 (NCT06662383) randomised about 800 adults with obesity to retatrutide or tirzepatide, with weight change at 80 weeks as its main result. It started in November 2024 and its primary completion is estimated for November 2026.
Retatrutide vs Mounjaro: what is the difference?
Mounjaro is the brand name of tirzepatide for type 2 diabetes; Zepbound is the same molecule for weight management. So retatrutide vs Mounjaro is the same comparison as retatrutide vs tirzepatide: one more receptor, glucagon, and no approval yet.
Does retatrutide have more side effects than tirzepatide?
The same kind, mostly nausea, diarrhoea and constipation, but more often at the top dose. In TRIUMPH-1, 11.3 % of the 12 mg group stopped because of adverse events, against 6.2 % on tirzepatide 15 mg in SURMOUNT-1. Separate trials, so the comparison is approximate.