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Retatrutide: what the research shows, and what it doesn’t

By Pinnacle Pulse Editorial Team · Status as of 16 October 2026 · Next scheduled update: 14 January 2027

Short answer: Retatrutide is an investigational weekly injection from Eli Lilly that acts on three hormone receptors at once: GLP-1, GIP and glucagon. Phase 3 trials published in 2026 reported significant weight loss and better blood sugar control than placebo, with mostly gastrointestinal side effects. It has not been approved for any use, and FDA says it cannot legally be compounded.

What retatrutide is

The weight-loss drugs of the past few years work by mimicking gut hormones. Semaglutide acts on one receptor, GLP-1. Tirzepatide acts on two, GLP-1 and GIP. Retatrutide, known in early papers by its code LY3437943, adds a third: the receptor for glucagon, a hormone that among other things raises energy use and acts on the liver. Hence the label “triple agonist” or, in the trial reports, “triple hormone receptor agonist”.

It is a peptide, injected under the skin once a week. Everything known about it comes from trials funded by its developer, and several of the authors on each paper are company employees. That is normal for a drug at this stage. It is worth knowing anyway.

What has been studied

Phase 2, 2023

Two phase 2 trials came out in 2023. The first, in the New England Journal of Medicine, enrolled 338 adults with obesity or overweight for 48 weeks. Weight fell substantially compared with placebo. Gastrointestinal side effects were the most common and were dose-related, and heart rate rose in a dose-dependent way, peaking at 24 weeks and then declining. The second, in the Lancet, tested retatrutide in people with type 2 diabetes and reported improvements in blood sugar and weight.

Phase 3, 2026

The phase 3 program, called TRIUMPH for obesity and TRANSCEND for diabetes, began reporting this year.

TRIUMPH-1 (NEJM, published online 29 September 2026) randomized 2,339 adults with obesity but without diabetes to retatrutide or placebo for 80 weeks. It had three primary questions. Did body weight change, did knee pain change in 574 participants with knee osteoarthritis, and did breathing interruptions during sleep change in 243 with obstructive sleep apnea? On all three, retatrutide did significantly better than placebo. The most common adverse events were gastrointestinal.

TRIUMPH-2 (Lancet, 2026) enrolled 1,152 adults with obesity and type 2 diabetes at 92 centres in eight countries, also for 80 weeks. Weight fell significantly more than with placebo, and blood sugar control improved. The side-effect figures are where the detail is:

  • Diarrhoea affected 27 to 34 percent of those on retatrutide, depending on dose, against 13 percent on placebo.
  • Nausea affected 14 to 28 percent, against 8 percent.
  • Low blood pressure and dysaesthesia, an abnormal and sometimes unpleasant skin sensation, were also more common. Dysaesthesia was reported in 4 to 7 percent on retatrutide and 1 percent on placebo.
  • Stopping treatment permanently because of adverse events or death happened in 4 to 12 percent on retatrutide, against 5 percent on placebo. The rate was highest at the middle dose.
  • Six people died on retatrutide and one on placebo. Investigators judged all deaths unrelated to the study drug.

TRANSCEND-T2D-1 (Lancet, 2026) tested retatrutide on its own in 537 adults with type 2 diabetes not controlled by diet and exercise, at sites in the US, Mexico and India, for 40 weeks. HbA1c, the long-term blood sugar measure, fell more than with placebo. Between 2 and 5 percent stopped because of side effects, against none on placebo. No severe hypoglycaemia was reported. Two deaths, both in the same retatrutide group, were judged unrelated to the drug.

What the research does not show

The trials don't yet show effects on heart attacks, strokes or survival. None of the published phase 3 studies were designed to answer that.

They don’t show what happens after 80 weeks, or after people stop. Long-term data, and data on rare side effects, will only come with more time and more patients.

They don’t explain all the safety signals. The papers report dysaesthesia and, in phase 2, a rise in heart rate, but not why they happen. The glucagon component is also what sets retatrutide apart from the drugs with longer track records.

And none of these results apply to products sold online as “retatrutide” for research. Those are not the trial drug, and FDA says it has seen products falsely labelled “for research purposes” sold for human use.

Status as of 16 October 2026. EU and US: retatrutide is investigational, with phase 3 trials registered on ClinicalTrials.gov, and is not approved for any use (no entry in EMA’s medicines data or in Drugs@FDA). FDA states that retatrutide “cannot be used in compounding under federal law” because it is not a component of an approved drug and has not been found safe and effective for any condition. WADA: retatrutide is not named on the 2027 Prohibited List. Class S0 covers pharmacological substances not addressed elsewhere on the List and without approval for human therapeutic use, and gives drugs in clinical development as an example. Only semaglutide and tirzepatide are on WADA’s 2027 monitoring program among GLP-1 drugs.

FAQ

Is retatrutide approved?

No. As of October 2026 it is an investigational drug in phase 3 trials. FDA states that it has not been found safe and effective for any condition and cannot be used in compounding.

How is retatrutide different from semaglutide and tirzepatide?

Semaglutide acts on the GLP-1 receptor, tirzepatide on the GLP-1 and GIP receptors. Retatrutide acts on those two plus the glucagon receptor.

What side effects were seen in the trials?

Mostly gastrointestinal: diarrhoea, nausea and vomiting, more common at higher doses. Trials also reported increases in heart rate, low blood pressure and dysaesthesia, an abnormal skin sensation, more often than with placebo.

Sources

  • Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389(6):514-526. PMID 37366315
  • Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet. 2023;402(10401):529-544. PMID 37385280
  • Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity. N Engl J Med. 2026 (online 29 September). TRIUMPH-1, NCT05929066. PMID 42814954
  • Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. 2026;408(10563):1455-1472. NCT05929079. PMID 42810372
  • Bajaj HS, et al. Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet. 2026;407(10546):2402-2413. NCT06354660. PMID 42250575
  • FDA. FDA’s concerns with unapproved GLP-1 drugs used for weight loss (content current as of 1 October 2026). fda.gov
  • WADA. 2027 Prohibited List, class S0, and 2027 Monitoring Program. wada-ama.org
  • EMA. Download medicine data: table of all medicines assessed by EMA (Excel), checked 16 October 2026. ema.europa.eu
  • FDA. Drugs@FDA, database of FDA-approved drugs, checked 16 October 2026. accessdata.fda.gov
  • ClinicalTrials.gov. Registered phase 3 trials of retatrutide (14 records), checked 16 October 2026. clinicaltrials.gov
  • WADA. 2027 Prohibited List, full text (PDF), checked 16 October 2026. wada-ama.org
  • WADA. 2027 Monitoring Program (PDF), checked 16 October 2026. wada-ama.org

Facts last checked: 16 October 2026.

About this article

Written by: the Pinnacle Pulse Editorial Team, the people who make the Pinnacle Pulse app. We work only from primary sources such as regulators, legal texts, trial registries and PubMed, and we remove claims we can’t check against one.

This article has not been reviewed by a physician. It is general information, not medical advice.

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Change log

  • 16 October 2026: First published.

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