Retatrutide vs CagriSema vs tirzepatide: the next-generation scorecard

Three ways to hit the same target

All three drugs build on GLP-1, the gut hormone behind semaglutide, and add something different. Tirzepatide High is one molecule that acts on both the GIP and GLP-1 receptors. CagriSema High is two molecules injected together: semaglutide for GLP-1 and cagrilintide, an amylin analogue, for the separate amylin satiety signal. Retatrutide Medium is one molecule that acts on three receptors, GIP, GLP-1 and glucagon; its discovery paper describes a design weighted toward GIP, with glucagon added for its effects on energy use and liver fat ¹.

The scorecard, trial by trial

Each row is the drug's main phase 3 obesity trial or its head-to-head, at the highest dose, with the estimand the published paper uses for its primary result. As of October 2, 2026:

The sources: TRIUMPH-1 ², REDEFINE 1 ³, SURMOUNT-1 ⁴, TRIUMPH-2 ⁵, REDEFINE 2 ⁶, SURMOUNT-2 ⁷ and SURMOUNT-5 ⁸.

Why the numbers are not a straight race

The estimand matters more than most headlines admit. TRIUMPH-1's paper reports -25.0% at 12 mg by counting everyone who was randomized, including people who stopped; Lilly's topline release in May 2026 led with 28.3%, which estimates the effect in people who stayed on treatment ^{2 9}. CagriSema has the same split: 20.4% for everyone randomized, about 22.7% under the trial-product estimand ³. Compare like with like, and the counting-everyone figures in the table are the fair basis.

The trials also ran for different lengths, 68 to 80 weeks, and longer trials tend to show more weight loss for drugs that have not plateaued. Placebo groups lost 3.0% to 3.9%, so the drug-minus-placebo gaps are about 21 points for retatrutide, about 18 points for tirzepatide and about 17 points for CagriSema. In people with type 2 diabetes, every drug loses weight more slowly, and the order is the same: retatrutide, then tirzepatide, then CagriSema.

Direct comparisons are what settle questions like these, and there are few. SURMOUNT-5 found tirzepatide ahead of semaglutide, 20.2% against 13.7% at 72 weeks ⁸. In February 2026 Novo Nordisk reported that CagriSema had lost its head-to-head trial against tirzepatide ¹⁰. No trial comparing retatrutide head-to-head with either drug has published.

Side effects and stopping

All three cause the same kind of side effects, mostly in the gut. In SURMOUNT-1, adverse events led 6.2% of people on tirzepatide 15 mg to stop, against 2.6% on placebo ⁴. In REDEFINE 1, gastrointestinal events affected 79.6% of those on CagriSema against 39.9% on placebo, mostly transient and mild to moderate ³. In TRIUMPH-2, diarrhoea affected 27% to 34% on retatrutide against 13%, and nausea 14% to 28% against 8% ⁵; in TRIUMPH-1 the most common adverse events were gastrointestinal ². Lilly's topline report for TRIUMPH-4, a trial in knee osteoarthritis, put stopping for adverse events at 18.2% on the 12 mg dose ¹¹, a figure to watch as the full papers appear.

Where each stands (as of October 2, 2026)

Tirzepatide is approved in the US as Mounjaro for type 2 diabetes (May 2022) and Zepbound for weight management (November 2023) ¹². CagriSema was filed with the FDA in December 2025, with a decision expected in late 2026 ¹³; we found no announced decision as of October 2, 2026. Retatrutide is not approved anywhere; Lilly said on August 5, 2026 that its data package is complete and that it plans to submit to the FDA in the first quarter of 2027 ¹⁴. A filing starts a review; it does not set an approval date.

Until then, the only one of the three a doctor can prescribe in the US is tirzepatide. Products sold online under the other two names are not the trial drugs; our guide to the gray-market code names explains what those listings usually contain.

Frequently asked questions

Is retatrutide better than tirzepatide?

In its phase 3 trial retatrutide produced more weight loss: 25.0% at 80 weeks against 20.9% at 72 weeks for tirzepatide in SURMOUNT-1, both counting everyone randomized. The trials were separate, and no head-to-head trial has published.

Is CagriSema better than Zepbound?

Not on the evidence so far. REDEFINE 1 found 20.4% weight loss at 68 weeks against 20.9% for tirzepatide 15 mg in SURMOUNT-1, and Novo Nordisk reported in February 2026 that CagriSema lost a head-to-head trial against tirzepatide.

Why do retatrutide figures differ between 25% and 28%?

They use different estimands. The published TRIUMPH-1 paper reports 25.0% at 12 mg counting everyone randomized; Lilly's topline figure of 28.3% estimates the effect in people who stayed on treatment.

When will retatrutide and CagriSema be available?

As of October 2, 2026, neither is approved. CagriSema has been under FDA review since December 2025, and Lilly plans to file retatrutide in the first quarter of 2027.

Related on Grey Peptides

• Retatrutide
• CagriSema
• Semaglutide vs tirzepatide

Sources

1. Coskun, T., et al. (2022). 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 Metab, 34(9), 1234-1247.e9. PMID: 35985340
2. Jastreboff, A. M., et al. (2026). Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med, . PMID: 42814954 · doi:10.1056/NEJMoa2604169
3. Garvey, W. T., et al. (2025). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med, 393(7), 635-647. PMID: 40544433 · doi:10.1056/NEJMoa2502081
4. Jastreboff, A. M., et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med, 387(3), 205-216. PMID: 35658024 · doi:10.1056/NEJMoa2206038
5. Bellido, V., et al. (2026). Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet, . PMID: 42810372
6. Davies, M. J., et al. (2025). Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med, 393(7), 648-659. PMID: 40544432
7. Garvey, W. T., et al. (2023). Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet, 402(10402), 613-626. PMID: 37385275
8. Aronne, L. J., et al. (2025). Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med, 393(1), 26-36. PMID: 40353578 · doi:10.1056/NEJMoa2416394
9. Eli Lilly. Topline results from TRIUMPH-1, May 21, 2026, as reported in our Wire post of May 22, 2026; read October 2, 2026.
10. Clinical Trials Arena. Novo Nordisk's CagriSema bested by Lilly's Zepbound in head-to-head trial, February 23, 2026; read October 2, 2026.
11. Eli Lilly. TRIUMPH-4 topline results, December 2025, as recorded on our retatrutide entry; read October 2, 2026.
12. Grey Peptides dataset, tirzepatide record (Drugs@FDA approvals of Mounjaro, May 2022, and Zepbound, November 2023); read October 2, 2026.
13. CNBC. Healthy Returns: What's next for Novo Nordisk's next-generation obesity drug CagriSema after trial miss, February 24, 2026; read October 2, 2026.
14. Eli Lilly. Second-quarter 2026 results, August 5, 2026 (filed with the SEC), as reported in our Wire post of September 30, 2026; read October 2, 2026.

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose.