The short version
- Mounjaro (tirzepatide) is an approved dual GIP and GLP-1 receptor agonist dosed at 2.5 to 15 mg once weekly; retatrutide is an investigational triple agonist that adds the glucagon receptor and was dosed at 1 to 12 mg in trials.
- In SURMOUNT-1 (72 weeks, 2,539 adults) tirzepatide produced mean weight change of -15.0% at 5 mg, -19.5% at 10 mg and -20.9% at 15 mg; in the retatrutide phase 2 trial (48 weeks, 338 adults) 8 mg gave -22.8% and 12 mg gave -24.2%.
- A milligram of retatrutide and a milligram of tirzepatide are not equivalent: the molecules differ in receptor profile and potency, so their dose ladders cannot be compared number for number.
- The two sets of results come from different trials, phases, populations and durations; no head-to-head randomised comparison has been published.
What each molecule is
Mounjaro is the brand name of tirzepatide, a once-weekly peptide from Eli Lilly that activates two receptors, GIP and GLP-1. It is approved for type 2 diabetes and, under the name Zepbound in the United States, for chronic weight management. Retatrutide (LY3437943) is Lilly's next molecule in the series: a single peptide that activates three receptors, GIP, GLP-1 and glucagon. It has completed phase 2 and is in phase 3; it is not approved anywhere.
The third receptor is the whole point. The Cell Metabolism discovery paper describes the design: balanced activity at the glucagon and GLP-1 receptors with more GIP receptor activity, and in mice, weight loss "augmented by the addition of GCGR-mediated increases in energy expenditure to GIPR- and GLP-1R-driven calorie intake reduction". Tirzepatide reduces intake; retatrutide is built to reduce intake and raise expenditure at the same time.
The two dose ladders
| Feature | Mounjaro (tirzepatide) | Retatrutide |
|---|---|---|
| Receptors | GIP, GLP-1 | GIP, GLP-1, glucagon |
| Status | approved (2022) | investigational, phase 3 |
| Frequency | once weekly, subcutaneous | once weekly, subcutaneous |
| Starting dose | 2.5 mg (label) | 2 mg in most phase 2 arms |
| Doses studied for weight | 5, 10, 15 mg (SURMOUNT-1) | 1, 4, 8, 12 mg (phase 2); 4, 9, 12 mg (phase 3) |
| Top dose | 15 mg | 12 mg |
| Escalation in the trial | 20 weeks (SURMOUNT-1) | to week 12 (phase 2); 16 weeks (phase 3) |
| Trial duration | 72 weeks | 48 weeks (phase 2); 80 weeks (TRIUMPH) |
The ladders look alike because both drugs are weekly peptides with gastrointestinal side effects that call for a slow climb. But the milligram figures are not interchangeable. A dose is a mass of a specific molecule, and the two molecules bind different receptors with different affinities. 12 mg of retatrutide is not "about 15 mg of tirzepatide"; it is 12 mg of retatrutide. The retatrutide ladder step by step is in the dosing schedule guide.
Mounjaro goes up to 15 mg, retatrutide to 12 mg. The numbers look close, but they are two different molecules, so 12 is not a smaller 15.
Weight loss in their respective trials
The bars below put the published mean weight changes side by side. Read the caption before the bars: they come from two separate trials of different length and phase.
Not a head-to-head. These bars come from two separate trials: phase 2 versus phase 3, 338 versus 2,539 people, 48 versus 72 weeks. They show what each paper reported, not which molecule wins.
On the numbers alone, retatrutide 8 mg at 48 weeks (-22.8%) already exceeds tirzepatide 15 mg at 72 weeks (-20.9%), and retatrutide 12 mg (-24.2%) sits 3.3 points above it. The retatrutide curve was also still descending at week 48, whereas the tirzepatide figure is a 72-week result closer to plateau. Those are the facts that drive the interest in retatrutide, and they are real. The next section is about why they are still not a comparison.
Why this is not a head-to-head
Four differences separate the two trials. Phase and size: SURMOUNT-1 was a phase 3 trial of 2,539 people; the retatrutide trial was a phase 2 trial of 338, with correspondingly wider uncertainty around each estimate. Duration: 72 weeks versus 48. Population: both enrolled adults with obesity or overweight plus a complication and excluded diabetes, but baseline weight, sex ratio and site mix differed (the retatrutide trial was 51.8% men, unusually high for an obesity trial). Estimand and analysis: the papers report different statistical treatments of participants who stopped, which alone can move a mean by a point or two.
Cross-trial comparisons in this field have misled before, and the only clean answer is a randomised head-to-head, which has not been published. What can be said is narrower and still useful: the largest weight loss reported for retatrutide at 48 weeks is larger than the largest reported for tirzepatide at 72 weeks, and the phase 3 program was sized to test whether that holds in thousands of people. The dose-by-dose figures for retatrutide, with confidence in their sources, are in the results page.
Retatrutide's bigger number came from a smaller, shorter trial. Only a trial that tests both drugs side by side can say which is stronger.
Escalation and tolerability compared
SURMOUNT-1 used a 20-week escalation from 2.5 mg in 2.5 mg steps every 4 weeks. The retatrutide phase 2 trial escalated to its top dose by week 12 with roughly doubling steps (2, 4, 8, 12 mg) and the phase 3 program lengthened that to 16 weeks.
Both trials describe gastrointestinal events as the most common adverse events, mostly mild to moderate and concentrated during escalation. The retatrutide paper adds the specific finding that a 2 mg start partially mitigated those events compared with a 4 mg start, and a dose-dependent heart-rate increase that peaked at 24 weeks and then declined.
On what happens after stopping, tirzepatide has published data and retatrutide does not. In SURMOUNT-4, participants switched to placebo after 36 weeks regained 14.0% of body weight over the next 52 weeks while those who continued lost a further 5.5%. Nothing equivalent exists for retatrutide yet, a point developed in the cycle length guide.
Approval status and what it means for dose
Mounjaro has a label, so it has an approved dose range and a defined escalation. Retatrutide has neither. Its dose range exists only as trial arms, the highest of which is 12 mg, and the phase 3 selection of 4, 9 and 12 mg is the closest thing to a consensus.
The first phase 3 publication, TRANSCEND-T2D-1 in the Lancet (June 2026), reported -11.5%, -13.9% and -15.3% weight change at 4, 9 and 12 mg over 40 weeks in adults with type 2 diabetes, a population in which incretin drugs generally produce smaller weight losses than in people without diabetes. Until TRIUMPH publishes, the complete dose picture for retatrutide is on the retatrutide dosage guide.
Questions readers ask
Is retatrutide stronger than Mounjaro?
The largest published retatrutide result (-24.2% at 12 mg over 48 weeks) exceeds the largest tirzepatide result (-20.9% at 15 mg over 72 weeks), but they come from different trials. No head-to-head trial has been published, so 'stronger' is an inference from separate studies, not a measured comparison.
Is 12 mg of retatrutide the same as 15 mg of Mounjaro?
No. They are different molecules with different receptor activities and potencies. The top trial dose of each is not a conversion of the other; the numbers happen to be in a similar range because both are once-weekly peptides of similar size.
Has a switch from Mounjaro to retatrutide been studied?
No published trial has studied a switch, and retatrutide is not approved for any use, so no clinical guidance on it exists. The only combination data with another incretin is the dulaglutide active-comparator arm in the diabetes trial, which was a parallel group, not a switch.
What does the glucagon receptor add?
In the preclinical work reported in Cell Metabolism, glucagon receptor activity increased energy expenditure on top of the intake reduction driven by GIP and GLP-1 receptor activity, which is the mechanistic argument for a triple agonist producing larger weight loss.
Sources
Reviewed against the primary sources on 21 Sep 2026. Every DOI resolves on CrossRef and every NCT number on ClinicalTrials.gov.
- Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. New England Journal of Medicine. 2023;389(6):514-526. doi.org/10.1056/NEJMoa2301972
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine. 2022;387(3):205-216. doi.org/10.1056/NEJMoa2206038
- Coskun T, Urva S, Roell WC, et al. 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;34(9):1234-1247. doi.org/10.1016/j.cmet.2022.07.013
- Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. The Lancet. 2026;407(10546):2402-2413. doi.org/10.1016/S0140-6736(26)00967-0
- Giblin A, et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. Diabetes, Obesity and Metabolism. 2025;28:83-93. doi.org/10.1111/dom.70209
- Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38-48. doi.org/10.1001/jama.2023.24945