What's New: October 2026 Update

• Full results are published. TRIUMPH-1 appeared in the New England Journal of Medicine and TRIUMPH-2 in The Lancet in late September 2026. The TRIUMPH-1 paper confirms the 28.3% and 25.0% figures used here and puts discontinuation because of side effects at 11.2% on 12 mg, against 4.6% on placebo.
• Filing planned for the first quarter of 2027. On July 23, 2026, the developer said it plans to submit a Biologics License Application then. Whether retatrutide legally counts as a biologic is still before the courts.
• A direct comparison is under way. TRIUMPH-5, which compares retatrutide with tirzepatide in about 800 adults with obesity, with or without type 2 diabetes, is expected to finish around December 2026. Until it reports, every retatrutide comparison on this page is across separate trials.

Retatrutide vs Tirzepatide vs Semaglutide: The Short Answer

Measured the same way, retatrutide produced the most weight loss of the three in its main Phase 3 trial: 28.3% if taken as intended, against 22.5% for tirzepatide and 16.9% for semaglutide. Counting everyone randomized, the figures are 25.0%, 20.9% and 14.9%. Retatrutide also had the highest share of people stopping because of side effects, and it is the only one of the three that is not approved.

These figures come from three separate trials, TRIUMPH-1, SURMOUNT-1 and STEP 1, which differed in length and population. No trial has yet compared retatrutide directly with either drug.

Why the Usual Numbers Don't Line Up

Obesity trials report results two ways. The efficacy estimand (semaglutide's developer calls its version the trial product estimand) estimates the effect if everyone had taken the drug as intended. The treatment-regimen estimand includes everyone randomized, including people who stopped early or never reached the top dose. The first number is always larger.

Retatrutide's 28.3% and tirzepatide's 22.5% are efficacy figures. Semaglutide's widely quoted 14.9% is the conservative one; its efficacy figure is 16.9%. The usual line-up therefore sets two optimistic numbers against one conservative number and reads the difference as pharmacology.

Measured consistently, retatrutide's advantage over semaglutide is about 67% on the as-intended basis and 68% across all participants, not the roughly 90% in circulation. Over tirzepatide it is 26% and 20%. The ordering never changes; the distance does.

The Three Trials

TRIUMPH-1: retatrutide

2,339 adults with obesity, without type 2 diabetes. 80 weeks; 4 mg, 9 mg and 12 mg against placebo, which lost 2.2% if taken as intended. Topline results May 21, 2026; published in full in September 2026. At 12 mg, 62.5% of participants lost at least a quarter of their body weight under the efficacy estimand, and 53.0% counting everyone randomized, according to the published paper.

The figure 28.7% is also often quoted for retatrutide. It comes from TRIUMPH-4, 445 adults with obesity and knee osteoarthritis, over 68 weeks. It is a real Phase 3 result, but from a specialty population less than a fifth the size of the two general-obesity trials it is usually set against. TRIUMPH-1 is the trial built for this comparison, and the difference between the two figures is four tenths of a point.

SURMOUNT-1: tirzepatide

2,539 adults with obesity or overweight. 72 weeks; 5 mg, 10 mg and 15 mg against placebo, which lost 2.4% if taken as intended. At 15 mg, 63% lost at least a fifth of their body weight under the efficacy estimand, 57% under the treatment-regimen estimand.

STEP 1: semaglutide

1,961 adults with obesity or overweight, 68 weeks at 2.4 mg. Under the treatment-policy estimand, 32.0% lost at least a fifth of their body weight, against 1.7% on placebo.

How Many Lost a Fifth of Their Body Weight

Counting everyone randomized, 66.8% of participants on retatrutide 12 mg lost at least a fifth of their body weight over 80 weeks, against 6.4% on placebo. The comparable figures are 57% for tirzepatide 15 mg over 72 weeks and 32.0% for semaglutide 2.4 mg over 68 weeks. The trials ran for different lengths, so this too is a comparison across separate trials.

How the Three Drugs Work

Semaglutide acts on the GLP-1 receptor: it slows gastric emptying, reduces appetite and improves the insulin response. It is sold as Ozempic for type 2 diabetes and Wegovy for weight management.

Tirzepatide adds the GIP receptor, which enhances insulin release and, according to its developer, also reduces food intake. It has the lowest nausea rate of the three despite acting on two receptors rather than one, and why that is remains unsettled.

Retatrutide adds the glucagon receptor. Its developer's medical information describes this as intended to help maintain energy expenditure during weight loss, so retatrutide may act on energy burned as well as energy eaten, a plausible contributor to its larger weight loss.

Side Effects Compared

Tirzepatide had the lowest rate on every measure here. Retatrutide and semaglutide were close to identical on the common gastrointestinal events (nausea 42.4% against 44.2%, diarrhea 32.0% against 31.5%, vomiting 25.3% against 24.8%, constipation 26.1% against 23.4%), yet retatrutide's discontinuation rate was about 1.6 times semaglutide's and 1.8 times tirzepatide's. The published TRIUMPH-1 paper also reports that 5.3% of participants on 12 mg stopped because they or the site investigator considered their weight loss excessive or sufficient.

Every figure here except dysesthesia comes from each drug's own pivotal trial rather than from pooled analyses; the dysesthesia figures for tirzepatide and semaglutide come from their US labels. The full list for retatrutide is in retatrutide side effects.

Dysesthesia

Dysesthesia is an altered sense of touch: tingling, burning, or ordinary contact registering as unpleasant. In TRIUMPH-1, 12.5% of participants on 12 mg reported it against 0.9% on placebo; in TRIUMPH-4, 20.9% against 0.7%. Related events had already appeared in the Phase 2 trial, which reported cutaneous hyperesthesia and skin sensitivity in 7% of participants on retatrutide and 1% on placebo.

It is not retatrutide's alone, although it was reported far more often than with tirzepatide. Semaglutide's US label lists it at 2% against 1% on placebo in the three trials pooled for the 2.4 mg dose, and at 22% on 7.2 mg and 6% on 2.4 mg, against 0.3% on placebo, in the later trials that tested the higher dose. Tirzepatide's US label reports it in 0.4% of patients on 15 mg, against 0.1% on placebo. These figures come from different trials and may not count exactly the same terms, so the comparison is approximate.

The published TRIUMPH-1 paper describes these events as mostly mild or moderate and nonserious; for TRIUMPH-4, the company said they rarely led to discontinuation.

Dosing: Approved Labels vs a Trial Protocol

Semaglutide and tirzepatide have FDA labels that set the starting dose, each step up and the maximum. A label exists because the FDA reviewed the evidence and decided what was safe to tell a large population to do.

Retatrutide has no label and no approved dose. What exists is a trial protocol: the schedule one trial used, on a screened population, with monitoring and a clinician who could pause or lower the dose the moment something went wrong. The Phase 3 program studied maintenance doses of 4 mg, 9 mg and 12 mg under those conditions. A protocol records what happened in a trial; it is not instructions, and it does not transfer to a product bought online.

Approval Status of the Three Drugs

Semaglutide was approved for type 2 diabetes in 2017 and for weight management in June 2021.

Tirzepatide was approved for type 2 diabetes in May 2022 and for weight management in November 2023.

Retatrutide is not approved by the FDA or any other regulator, for any use. It is not available by prescription. Outside clinical trials, the developer said in August 2026 that it supplies it only to a limited number of patients who meet strict medical criteria and cannot enroll in a trial. Products sold online under the retatrutide name are not sold or supplied by the company, their contents are not verified, and no figure in this article describes them.

Cost Compared

Retatrutide has no price because it is not approved. Semaglutide's weight-management list price is $1,349.02 per package, and both manufacturers sell their GLP-1 medicines self-pay at lower prices; tirzepatide single-dose vials, for example, cost $299 to $449 a month at the manufacturer's self-pay prices, depending on the dose. The Medicare GLP-1 Bridge demonstration, running July 1, 2026 through December 31, 2027, puts eligible beneficiaries at $50 a month. Current prices and coverage are covered in how much retatrutide may cost.

What the Data Supports

Tirzepatide has the stronger numbers among the drugs that can be prescribed: more weight loss than semaglutide under either estimand, the lowest nausea rate of the three and the lowest discontinuation rate, 6.2%.

Semaglutide has the longest record in weight management, about five years, and a 7.0% discontinuation rate. Its weight loss is the lowest of the three, though by less than the usual figures suggest.

Retatrutide produced the most weight loss and is the only one of the three that targets the glucagon receptor. It also had the highest discontinuation rate, and it cannot be prescribed. Another next-generation candidate, CagriSema, has already been tested head to head against tirzepatide.

Retatrutide vs Tirzepatide vs Semaglutide in Summary

The efficacy gradient is real: 16.9%, 22.5% and 28.3% if each drug is taken as intended; 14.9%, 20.9% and 25.0% across all participants. What the usual comparison overstates is the distance, because it sets an as-intended number against an all-participants one.

The gradient runs the other way for tolerability. Retatrutide's discontinuation rate in TRIUMPH-1 was 1.6 to 1.8 times that of either approved drug in its pivotal trial, and dysesthesia, reported by one in eight participants at 12 mg in TRIUMPH-1, was more common than on tirzepatide or on semaglutide 2.4 mg, though less common than on semaglutide 7.2 mg. Two of these drugs can be prescribed today; the third has not yet been submitted for approval.

Sources

• Eli Lilly. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026. (TRIUMPH-1)
• Eli Lilly. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026. (TRIUMPH-2, TRIUMPH-3)
• Eli Lilly. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. December 11, 2025. (TRIUMPH-4)
• Eli Lilly. Lilly's SURMOUNT-1 results published in The New England Journal of Medicine show tirzepatide achieved between 16.0% and 22.5% weight loss in adults with obesity or overweight. June 4, 2022. (Both estimands.)
• Jastreboff AM, Kaplan LM, Frías JP, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514–526.
• Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205–216.
• Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989–1002.
• Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026. DOI: 10.1056/NEJMoa2604169. (TRIUMPH-1)
• Eli Lilly statement on pre-approval access to retatrutide, reported August 2026.
• Novo Nordisk. Wegovy (semaglutide) US prescribing information, section 6.1. Revised June 2026.
• Eli Lilly. US prescribing information for tirzepatide for weight reduction, section 6.1. Revised August 2026.
• Lilly Medical. What is the mechanism of action of retatrutide?
• Centers for Medicare & Medicaid Services. Medicare GLP-1 Bridge: GLP-1 Drugs for $50 a Month. 2026.
• U.S. Food and Drug Administration. Approval records for semaglutide (2017, June 2021) and tirzepatide (May 2022, November 2023).
• Eli Lilly. LillyDirect self-pay pricing for tirzepatide. September 2026.

Medical Disclaimer: This article is for informational purposes only and is not medical advice. Retatrutide is investigational and is not approved by the FDA for any use. It is not available by prescription, and products sold online under its name are not sold or supplied by Lilly. Semaglutide and tirzepatide are prescription medications. Nothing here is a recommendation to use, seek out, switch or avoid any medication.