- Retatrutide is an investigational drug. It is not approved anywhere, and there is no lawful consumer source in the US. Products sold online under its name are unapproved drugs.
- It acts on three receptors: GLP-1, GIP and glucagon. Semaglutide acts on one of these and tirzepatide on two.
- In the phase 2 trial (Jastreboff et al., NEJM 2023), the highest retatrutide arm lost an average of 24.2% of body weight at 48 weeks.
- Eli Lilly reported phase 3 TRIUMPH-1 results in May 2026: an average 28.3% weight loss at 80 weeks in the highest retatrutide arm, against 3.9% on placebo.
- Its trials have not reported results by genotype, so no study has tested whether any gene variant changes response to it.
Retatrutide is an investigational weight loss drug from Eli Lilly that acts on three hormone receptors at once. Its trial results have drawn a great deal of attention, and products sold online under its name have followed. This page sets out what the trials reported, how the drug is thought to work, and where it stands legally.
This page is education about published and announced trial results. Retatrutide is not approved anywhere and there is no lawful consumer source in the US. Nothing here is a recommendation to obtain or use it.
How is retatrutide different from semaglutide and tirzepatide?
The three drugs act on different combinations of receptors for gut and pancreatic hormones:
GLP-1 receptor
The receptor semaglutide acts on. Activating it slows stomach emptying, reduces appetite through the brain, and increases insulin release when blood sugar is high.
GIP receptor
The second receptor tirzepatide adds. GIP is another gut hormone involved in insulin release and fat metabolism.
Glucagon receptor
The third receptor retatrutide adds. Glucagon raises blood sugar, but glucagon receptor activation in the liver is also linked to increased fat oxidation and energy expenditure in research.
The idea behind adding glucagon is that its effect on energy expenditure adds to the appetite effect of the other two, while the GLP-1 component offsets glucagon's tendency to raise blood sugar. How much of retatrutide's effect comes from each receptor in people has not been separated out in published data.
What did the trials report?
Phase 2. Jastreboff et al. (New England Journal of Medicine, 2023) randomised adults with obesity to one of several retatrutide arms or placebo for 48 weeks. The highest retatrutide arm lost an average of 24.2% of body weight.
Phase 3. Eli Lilly announced TRIUMPH-1 results on 21 May 2026. In 2,339 adults with obesity followed for 80 weeks, the company reported:
| Arm (TRIUMPH-1, 80 weeks) | Average weight loss reported |
|---|---|
| Retatrutide, lowest arm | 17.6% |
| Retatrutide, middle arm | 23.7% |
| Retatrutide, highest arm | 28.3% |
| Placebo | 3.9% |
Lilly also reported that about 45% of participants in the highest retatrutide arm lost 30% or more of their starting weight. A second phase 3 trial, TRIUMPH-4, in people with obesity and knee osteoarthritis, reported results in December 2025. These figures come from company announcements; full peer-reviewed publication of TRIUMPH-1 will allow them to be checked in detail.
Average body weight loss reported for the highest retatrutide arm of TRIUMPH-1 at 80 weeks, against 3.9% on placebo. Source: Eli Lilly TRIUMPH-1 announcement, May 2026.
Comparing across trials
It is tempting to set these numbers beside the pivotal trials of other drugs, such as STEP-1 for semaglutide (68 weeks) and SURMOUNT-1 for tirzepatide (72 weeks). Those trials differed in length, population and design, so side-by-side percentages are not a fair head-to-head. Only a trial that randomises people to the drugs being compared can answer which works better.
What side effects were reported?
The most common adverse events matched the GLP-1 drug class: nausea, diarrhoea, constipation and vomiting. Lilly reported nausea in roughly a third of participants in the highest retatrutide arm, and discontinuation because of adverse events rising across the arms, from 4.1% in the lowest arm to 11.3% in the highest. Gastrointestinal effects were more frequent in the higher arms.
Because retatrutide is not approved, there is no label, no established long-term safety record and no regulator-reviewed list of contraindications.
Is retatrutide approved or available?
No. Retatrutide is an investigational drug and is not approved by FDA or any other regulator. It cannot lawfully be compounded in the US. FDA treats products sold online as retatrutide, including those labelled "for research use only", as unapproved drugs that are illegal to sell to consumers, and in 2026 Eli Lilly filed lawsuits against sellers of such products. Outside of clinical trial participants, no one receives retatrutide lawfully.
Does genetics predict response to retatrutide?
Not on current evidence. Variants in GLP1R, the gene for the GLP-1 receptor, have been linked in human studies to differences in weight loss on semaglutide and tirzepatide. Retatrutide also acts on the GIP and glucagon receptors, encoded by GIPR and GCGR, and none of its trials has reported results by genotype.
No study has tested whether any gene variant changes response to retatrutide. A DNA report can show which versions of these receptor genes you carry and what the research on other GLP-1 drugs found; it cannot predict how retatrutide would work for you.
Verdict: retatrutide's reported trial results are large, and its three-receptor mechanism is genuinely different from semaglutide's and tirzepatide's. It is still an investigational drug: unapproved, without a label, and with no lawful consumer source. Products sold online under its name are not the drug that was tested in these trials.
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What did the retatrutide trials find?
In the phase 2 trial (Jastreboff et al., NEJM 2023), the highest retatrutide arm lost an average of 24.2% of body weight at 48 weeks. Eli Lilly reported phase 3 TRIUMPH-1 results in May 2026: an average 28.3% loss at 80 weeks in the highest retatrutide arm, against 3.9% on placebo.
Is retatrutide approved by the FDA?
No. Retatrutide is an investigational drug and is not approved by FDA or any other regulator. There is no lawful consumer source in the US.
How is retatrutide different from tirzepatide?
Tirzepatide acts on the GLP-1 and GIP receptors. Retatrutide adds a third, the glucagon receptor, which research links to increased fat oxidation and energy expenditure. No trial has compared the two directly.
What side effects were reported for retatrutide?
The most common were nausea, diarrhoea, constipation and vomiting, as with other GLP-1 drugs. Lilly reported discontinuation because of adverse events rising across the arms in TRIUMPH-1, from 4.1% in the lowest arm to 11.3% in the highest.
Is retatrutide legal to compound or sell online?
No. It cannot lawfully be compounded in the US, and FDA treats products sold online as retatrutide, including those labelled for research use, as unapproved drugs. Its only lawful use is in clinical trials.
Do genes predict how well retatrutide works?
No study has tested that. GLP1R variants have been linked to differences in weight loss on semaglutide and tirzepatide, but retatrutide's trials have not reported results by genotype.
This article is for informational and educational purposes only. It reports what published research found; it is not medical advice, it does not diagnose, treat, cure or prevent any disease, and nothing in it is a dose or a recommendation to use any compound. Talk to a licensed clinician about any medical decision.