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Retatrutide vs Tirzepatide: What the Trials Show, and What Is Not Known Yet

One is approved and priced; the other is in Phase 3 with a filing planned for 2027. The SURMOUNT and TRIUMPH trial numbers side by side, with the reasons they cannot be read as a head-to-head.

The glp1ledger editorial team · Published 2026-09-05

Tirzepatide is a medicine you can be prescribed today. Retatrutide is a molecule in Phase 3 trials whose maker plans to ask FDA for approval in early 2027. That difference governs everything else on this page: one drug has a label, a price and four years of prescribing; the other has a set of company press releases and a design paper. We put the trial numbers side by side because people ask, and we explain, at each step, why the two columns cannot be subtracted from each other.

This page reports trial results and regulatory facts. It does not say which medicine a person should take, and it will not: that is a question for the person and their clinician, as our editorial standards set out.

What each one is

Both are once-weekly injections made by Eli Lilly. Tirzepatide activates two gut-hormone receptors, GIP and GLP-1; it is sold as Mounjaro for type 2 diabetes and as Zepbound for weight management. FDA approved Zepbound under NDA 217806 on 2023-11-08 and added a new indication on 2024-12-20 (Drugs@FDA). Retatrutide activates three receptors, GIP, GLP-1 and glucagon; the glucagon activity is the intended difference, and it is why the drug is called a triple agonist. Lilly's design paper for the TRIUMPH program describes it as "a novel synthetic molecule" studied in "over 5800 participants" across four Phase 3 trials (Giblin et al., Diabetes, Obesity and Metabolism 2025).

The trials, side by side

Tirzepatide: SURMOUNT-1 Retatrutide: TRIUMPH-1
Published where New England Journal of Medicine, 2022, peer-reviewed Lilly press release, 2026-05-21; no journal paper as of 2026-09-05
Participants 2,539 adults, BMI 30 or more (or 27 with a complication), no diabetes 2,339 adults with obesity or overweight, no diabetes
Length 72 weeks, including 20 weeks of dose escalation 80 weeks; 104-week extension for a subset
Mean weight change, by dose 5 mg −15.0%; 10 mg −19.5%; 15 mg −20.9% 4 mg −19.0% (−47.2 lb); 9 mg −25.9% (−64.4 lb); 12 mg −28.3% (−70.3 lb)
Placebo −3.1% −2.2%
How dropouts were counted Treatment-regimen estimand: effects regardless of stopping, intention-to-treat Efficacy estimand for the headline figures; the release also reports 17.6%, 23.7% and 25.0% versus 3.9% on placebo when everyone is counted regardless of stopping
Lost 20% or more 10 mg 50%; 15 mg 57%; placebo 3% Not stated in the release
Stopped because of adverse events 5 mg 4.3%; 10 mg 7.1%; 15 mg 6.2%; placebo 2.6% 4 mg 4.1%; 9 mg 6.9%; 12 mg 11.3%; placebo 4.9%
Most common adverse events Gastrointestinal, mostly mild to moderate, mostly during escalation At 12 mg vs placebo: nausea 42.4% vs 14.8%; diarrhea 32.0% vs 13.5%; constipation 26.1% vs 10.9%; vomiting 25.3% vs 4.8%

Sources: Jastreboff et al., NEJM 2022 (PubMed 35658024); Lilly TRIUMPH-1 release, 2026-05-21.

The 104-week extension of TRIUMPH-1 enrolled 532 participants with a BMI of 35 or more and escalated every arm, including the former placebo arm, to the maximum tolerated dose for a further 24 weeks. The release reports −27.9%, −29.5% and −30.3% for the three retatrutide arms and −19.2% for the placebo-to-retatrutide arm at 104 weeks. The last number is the useful one: people who spent 80 weeks on placebo and then 24 weeks on retatrutide lost 19.2%, which is a measure of the drug's effect over six months in a population already in a trial.

Why these two columns are not a comparison

Four reasons, each of which alone would be enough.

  1. Different estimands. SURMOUNT-1's headline numbers count everyone who was randomized, whether or not they stayed on the drug. TRIUMPH-1's headline numbers use the efficacy estimand, which describes the effect in people who took the drug as intended. Lilly's own release gives the all-comers figures for retatrutide as 17.6%, 23.7% and 25.0% against 3.9% on placebo. Compare those to tirzepatide's 15.0%, 19.5% and 20.9% against 3.1%, and the gap between the drugs shrinks from about seven points to about four at the top dose. Whichever pair is used, the placebo groups also differ (3.1% versus 3.9% or 2.2%), which is a reminder that the trials' populations and years were not the same.
  2. Different lengths. Seventy-two weeks against eighty. Weight loss on these drugs is still falling, slowly, at week 72, so an eight-week difference favors the longer trial by some fraction of a point.
  3. Different publication status. SURMOUNT-1 is a peer-reviewed paper with a supplementary appendix, a protocol, and four years of subsequent analysis. TRIUMPH-1 is a press release. Numbers in press releases have, in this field, matched the eventual paper closely, but the paper is where adverse-event tables, subgroups and the exact analysis populations live.
  4. No head-to-head. Lilly has run tirzepatide against semaglutide (SURMOUNT-5) but has not reported a trial of retatrutide against tirzepatide. Until one exists, any ranking of the two is an inference across trials, and the honest label for that inference is "probably, by some margin, in trials not designed to show it."

The other retatrutide trials, briefly

Lilly reported three further Phase 3 results, all by press release:

  • TRIUMPH-4 (2025-12-11): 445 adults with obesity or overweight and knee osteoarthritis, no diabetes, 68 weeks. Weight loss of 26.4% at 9 mg and 28.7% at 12 mg versus 2.1% on placebo (efficacy estimand). WOMAC pain scores fell 4.5 points (75.8%) at 9 mg and 4.4 points (74.3%) at 12 mg versus 2.4 points (40.3%) on placebo. Discontinuation for adverse events was 12.2% at 9 mg and 18.2% at 12 mg versus 4.0% on placebo, higher than in TRIUMPH-1. (Release)
  • TRIUMPH-2 (2026-07-23): 1,152 adults with type 2 diabetes and obesity or overweight, 80 weeks. Weight loss of 12.7%, 19.1% and 20.8% at 4, 9 and 12 mg versus 4.0% on placebo, and A1C reductions of up to 1.6 points. Discontinuation for adverse events 3.8%, 11.6% and 7.7% versus 4.9%.
  • TRIUMPH-3 (2026-07-23): 1,949 adults with severe obesity and established cardiovascular disease, with or without diabetes, 80 weeks. Weight loss of 21.6% at 9 mg and 22.6% at 12 mg versus 3.2% on placebo. Discontinuation for adverse events 9.8% and 13.5% versus 4.8%. (Release for both)

The pattern across the four trials is consistent: more weight loss than the placebo-controlled tirzepatide trials reported, and a higher rate of stopping for adverse events at the 12 mg dose, ranging from 7.7% in people with diabetes to 18.2% in the knee-osteoarthritis trial. Whether that trade-off holds up, and for whom, is what the eventual papers and the FDA review are for.

Approval and timing

Lilly's 2026-07-23 release says the TRIUMPH-2 and TRIUMPH-3 results complete "the clinical data package to support global submissions" for obesity, knee osteoarthritis pain and obstructive sleep apnea, and that the company "plans to submit a Biologics License Application (BLA) for retatrutide to FDA in Q1 2027". Nothing in that sentence is an approval date. Tirzepatide's own path is the reference: Zepbound was approved on 2023-11-08, roughly a year after its obesity data were in hand.

One consequence for readers: any product sold today as "retatrutide" is not this medicine. FDA's warning letters to research-chemical sellers naming retatrutide run from December 2024 (Summit Research Peptides, Prime Peptides) through March 2026 (Gram Peptides, Pink Pony Peptides, Prime Sciences, Mile High Compounds) to August 2026 (five sellers in one day). The letters, and what FDA said in each, are tracked on Peptifact's warning-letter page.

Cost

Tirzepatide has a price; retatrutide does not. On 2026-09-05 Lilly's LillyDirect self-pay price for Zepbound was $299 per month at 2.5 mg, $399 at 5 mg and $449 from 7.5 mg to 15 mg, against a list price the White House quoted at $1,088. Our cost page has the full table, the savings-card caps and the Medicare Bridge terms. Retatrutide's price, if approved, is unknown; Lilly has not indicated one.

What is not known

Retatrutide has no peer-reviewed Phase 3 publication as of 2026-09-05, no cardiovascular-outcomes result (a trial is running), no data past 104 weeks, and no head-to-head against any approved drug. Tirzepatide has all of those except a head-to-head against retatrutide. The glucagon activity that distinguishes retatrutide raises questions that the releases do not answer, including effects on heart rate and liver fat that the design paper names as endpoints in other TRIUMPH studies. When the papers appear, this page will change and say so.

Sources and dates

Opened 2026-09-05: Jastreboff et al., NEJM 2022 (SURMOUNT-1 abstract); Giblin et al., Diabetes, Obesity and Metabolism 2025 (TRIUMPH design); Lilly releases of 2025-12-11 (TRIUMPH-4), 2026-05-21 (TRIUMPH-1) and 2026-07-23 (TRIUMPH-2 and -3); Drugs@FDA entry for NDA 217806; Lilly's Zepbound coverage and savings page; the White House TrumpRx fact sheet of 2026-02-05; FDA warning letters as linked from the Peptifact tracker. Corrections go to the contact page.

Frequently asked questions

Is retatrutide better than tirzepatide for weight loss?

No trial has compared them, so nobody can say that from evidence. The largest placebo-controlled trials each drug has reported in adults without diabetes gave a mean loss of 20.9% at tirzepatide's top dose over 72 weeks (SURMOUNT-1) and 28.3% at retatrutide's top dose over 80 weeks (TRIUMPH-1, efficacy estimand). The trials differ in length, in how people who stopped the drug were counted, in the years they ran, and in their populations, and TRIUMPH-1 has been reported only in a company release, not a peer-reviewed paper. The numbers point the same way; they are not a comparison.

Is retatrutide FDA approved?

No. As of 2026-09-05 retatrutide is an investigational medicine. Lilly's release of 2026-07-23, reporting TRIUMPH-2 and TRIUMPH-3, says the company plans to submit a Biologics License Application to FDA in the first quarter of 2027. A submission is not an approval; FDA review of a new obesity medicine has typically taken most of a year after filing.

When will retatrutide be available?

Not before FDA acts on an application that Lilly plans to file in early 2027, so the earliest realistic date is late 2027, and that assumes a standard review and approval. Products sold online today under the name retatrutide are not the medicine in the trials: FDA has issued warning letters to sellers of 'research' retatrutide in December 2024, March 2026 and August 2026 for marketing unapproved drugs.

How much weight do people lose on tirzepatide?

In SURMOUNT-1, adults with obesity but not diabetes lost a mean of 15.0%, 19.5% and 20.9% of body weight at 5, 10 and 15 mg over 72 weeks, against 3.1% on placebo; 85% to 91% of those on tirzepatide lost at least 5%, and half of the 10 mg group and 57% of the 15 mg group lost 20% or more. The most common adverse events were gastrointestinal, mostly mild to moderate and mostly during dose escalation.

What are the side effects of retatrutide?

In TRIUMPH-1 the most common adverse events at 12 mg versus placebo were nausea (42.4% vs 14.8%), diarrhea (32.0% vs 13.5%), constipation (26.1% vs 10.9%) and vomiting (25.3% vs 4.8%); 11.3% of the 12 mg group stopped because of adverse events versus 4.9% on placebo. In TRIUMPH-4, in people with knee osteoarthritis, discontinuation for adverse events was 18.2% at 12 mg versus 4.0% on placebo. The full safety data have not been published in a journal as of 2026-09-05.

Does retatrutide help with knee pain?

TRIUMPH-4 (445 adults with obesity and knee osteoarthritis, 68 weeks) reported WOMAC pain scores falling by 4.5 points (75.8%) at 9 mg and 4.4 points (74.3%) at 12 mg, against 2.4 points (40.3%) on placebo, alongside weight loss of 26.4% and 28.7% versus 2.1%. That is a company release, not yet a peer-reviewed paper, and the trial was not designed to separate the effect of weight loss on the knee from any direct effect of the drug.