Investigational
Retatrutide: an investigational triple agonist (not FDA approved) Investigational: not FDA approvedPrescriptionInjection
Retatrutide's Phase 3 TRIUMPH results explained: weight loss by dose and trial, the two estimands, side effects including dysesthesia, and what comes next. Investigational, checked October 7, 2026.
Fact-checked against FDA labels and official sources; not yet reviewed by a licensed clinician. This page is education, not medical advice. Talk to your doctor before starting, stopping or changing any treatment.
Key takeaways
- Retatrutide is investigational: on 2026-10-07 the FDA had no approval record or label for it, and Lilly plans to submit it in Q1 2027.[3]
- In TRIUMPH-1 (2,339 adults with obesity, 80 weeks), average weight change was -25.0% on 12 mg vs -3.9% on placebo, counting everyone randomized.[1]
- In TRIUMPH-2 (1,152 adults with type 2 diabetes), it was -18.8% vs -5.1%; people with diabetes lost less, as with approved medicines.[2]
- Company headlines use the efficacy estimand (as if everyone stayed on the drug), which gives bigger numbers, such as -28.3% in TRIUMPH-1.[3]
- Digestive side effects rose with dose, and dysesthesia (unusual skin sensations) was reported in up to 20.9% on 12 mg in TRIUMPH-4 (company-reported).[7]
In short: Retatrutide, an investigational weekly injection from Eli Lilly, has now reported results from its main Phase 3 trials, and the numbers are the largest average weight losses seen so far in a medicine trial: in TRIUMPH-1, adults with obesity lost 25.0% of their body weight on the highest dose over 80 weeks, compared with 3.9% on placebo, counting everyone who started. People with type 2 diabetes lost less (18.8% vs 5.1% in TRIUMPH-2). Side effects were mostly digestive, rose with the dose, and included a less familiar skin-sensation effect called dysesthesia. Retatrutide is not FDA approved; Lilly plans to apply in the first quarter of 2027. Checked on October 7, 2026.
This article explains what each Phase 3 trial found, why the same trial can produce two different headline numbers, what the side effects looked like, and what still has to happen before an FDA decision. For the full drug profile, including how the three-hormone design works and the complete list of ongoing trials, see our retatrutide medication page. It is general education, not individual advice.
Retatrutide's Phase 3 program at a glance
- 2,339adults with obesity in TRIUMPH-1, the main weight trialJastreboff AM et al., NEJM 2026
- 25.0%average weight loss at 80 weeks on 12 mg, counting everyone randomized (placebo 3.9%)NEJM 2026
- 4core TRIUMPH trials with results reported by September 2026 (two peer reviewed)
- Q1 2027when Lilly plans to submit retatrutide to the FDAEli Lilly, Sept 29, 2026
Checked on October 7, 2026
First, how to read these numbers
Almost every retatrutide headline comes with two different percentages, and both can be correct. They answer different questions.
The treatment-regimen estimand counts everyone who was randomized, including people who stopped the drug early because of side effects or for any other reason. It is the closest a trial gets to “what happens if a group of people is prescribed this”. The efficacy estimand estimates what would have happened if everyone had stayed on the drug as planned. It is useful for understanding the drug’s biological effect, but it is always the bigger number. Lilly’s press releases use the efficacy estimand; its September 29, 2026 release says plainly that “all data in this press release represent the efficacy estimand”. The peer-reviewed papers report both. On this page we lead with the treatment-regimen figures from the journals and label every company figure as company-reported.
| Item | Treatment-regimen (everyone randomized) | Efficacy estimand (if all stayed on drug) |
|---|---|---|
| TRIUMPH-1, obesity, 80 wk | 25% | 28.3% |
| TRIUMPH-2, type 2 diabetes, 80 wk | 18.8% | 20.8% |
INVESTIGATIONAL. Bars show percent of starting body weight lost. Efficacy-estimand figures are company-reported.
Source: NEJM 2026 and The Lancet 2026 (treatment-regimen); Eli Lilly releases May 21 and Sept 29, 2026 (efficacy estimand) (checked on October 7, 2026)
TRIUMPH-1: adults with obesity, without diabetes
TRIUMPH-1 is the pivotal weight trial, published in the New England Journal of Medicine in September 2026. It enrolled 2,339 adults with obesity, or with overweight and a weight-related health problem, who did not have type 2 diabetes. They were randomly assigned to retatrutide at 4 mg, 9 mg or 12 mg once a week, or to placebo, for 80 weeks, alongside diet and activity counseling. Doses were reached in steps every four weeks, starting at 2 mg.
Counting everyone randomized, average weight change was -17.6% on 4 mg, -23.7% on 9 mg and -25.0% on 12 mg, compared with -3.9% on placebo. By the efficacy estimand, Lilly reported -28.3% on 12 mg. The trial also included 574 people with knee osteoarthritis and 243 with obstructive sleep apnea, and Lilly reported improvements in knee pain and in breathing interruptions during sleep in those groups. In a planned extension for people who started with a BMI of 35 or higher, Lilly reported -30.3% at 104 weeks (efficacy estimand, company-reported).
| Item | Value |
|---|---|
| Placebo | 3.9% |
| Retatrutide 4 mg | 17.6% |
| Retatrutide 9 mg | 23.7% |
| Retatrutide 12 mg | 25% |
INVESTIGATIONAL: not FDA approved. Treatment-regimen estimand: everyone randomized, including people who stopped. 2,339 adults with obesity and no diabetes.
Source: Jastreboff AM et al., New England Journal of Medicine 2026 (TRIUMPH-1) (checked on October 7, 2026)
One way to put the numbers in context: in the trials that led to approval of today’s leading medicines, average weight loss was 14.9% with semaglutide 2.4 mg (Wegovy) over 68 weeks in STEP 1, and 20.9% with tirzepatide 15 mg (Zepbound) over 72 weeks in SURMOUNT-1. Those were different trials, with different people, lengths and years, so the numbers cannot be compared directly. A direct answer will come from TRIUMPH-5, which tests retatrutide head to head against tirzepatide (see “What comes next” below). Our semaglutide vs tirzepatide comparison explains how the two approved molecules differ.
TRIUMPH-2: adults with type 2 diabetes
TRIUMPH-2, published in The Lancet and presented at the European Association for the Study of Diabetes meeting in September 2026, enrolled 1,152 adults with type 2 diabetes and a BMI of 27 or more for 80 weeks. Counting everyone randomized, weight changed by -11.9% (4 mg), -16.8% (9 mg) and -18.8% (12 mg) vs -5.1% on placebo, and 84% of participants completed treatment. Lilly’s efficacy-estimand figures were -12.7%, -19.1% and -20.8% vs -4.0%.
Blood sugar improved too. From an average HbA1c (a three-month blood sugar measure) of 7.7%, Lilly reported reductions of 1.4 to 1.6 points vs 0.2 on placebo, and 28.4% to 40.0% of people on retatrutide reached an HbA1c below 5.7%, the non-diabetes range, vs 4.4% on placebo (efficacy estimand, company-reported). People with type 2 diabetes usually lose less weight on these medicines than people without it, a pattern also seen with approved GLP-1 medicines. Our guide to type 2 diabetes and weight explains why.
TRIUMPH-3 and TRIUMPH-4: heart disease and knee osteoarthritis
TRIUMPH-3 enrolled about 1,950 adults with a BMI of 35 or more and established cardiovascular disease, with or without diabetes. In its July 23, 2026 topline release, Lilly reported weight changes of -21.6% (9 mg) and -22.6% (12 mg) vs -3.2% on placebo (efficacy estimand). It was not designed to show heart protection: heart attacks, strokes and cardiovascular deaths were fewer than expected in every group, and the hazard ratio of 1.12 (95% confidence interval 0.64 to 1.96) means the trial could not show a difference either way. A separate outcomes trial of about 10,000 people, TRIUMPH-Outcomes, is designed to answer that question; its primary completion is listed for 2029. No full TRIUMPH-3 paper had been published when we checked.
TRIUMPH-4 enrolled 445 adults with obesity or overweight and knee osteoarthritis for 68 weeks. In its December 11, 2025 release, Lilly reported treatment-regimen weight changes of -20.0% (9 mg) and -23.7% (12 mg) vs -4.6%, and knee pain scores that improved by up to 75.8% vs 40.3% on placebo. These results are company-reported and not yet peer reviewed.
| Trial | Who took part | Length | Weight change on 12 mg vs placebo | How it was reported |
|---|---|---|---|---|
| TRIUMPH-1 (NCT05929066) | 2,339 adults with obesity, no diabetes | 80 weeks | -25.0% vs -3.9% | Peer reviewed (NEJM 2026), treatment-regimen |
| TRIUMPH-2 (NCT05929079) | 1,152 adults with type 2 diabetes | 80 weeks | -18.8% vs -5.1% | Peer reviewed (Lancet 2026), treatment-regimen |
| TRIUMPH-3 (NCT05882045) | About 1,950 adults, BMI 35+, heart disease | 80 weeks | -22.6% vs -3.2% | Company topline, efficacy estimand |
| TRIUMPH-4 (NCT05931367) | 445 adults with knee osteoarthritis | 68 weeks | -23.7% vs -4.6% | Company topline, treatment-regimen |
Side effects: what the trials reported
Because there is no FDA label, the only safety information is what the trials have reported, much of it through company releases. As with the approved GLP-1 medicines, digestive side effects were the most common and rose with the dose. In TRIUMPH-1, Lilly reported nausea in 42.4% of people on 12 mg vs 14.8% on placebo, diarrhea in 32.0% vs 13.5%, constipation in 26.1% vs 10.9% and vomiting in 25.3% vs 4.8%. In TRIUMPH-2, rates were somewhat lower: nausea 28.0% vs 8.0% and vomiting 15.7% vs 4.2% on 12 mg.
| Item | TRIUMPH-1, retatrutide 12 mg | TRIUMPH-1, placebo | TRIUMPH-2, retatrutide 12 mg | TRIUMPH-2, placebo |
|---|---|---|---|---|
| Nausea | 42.4% | 14.8% | 28% | 8% |
| Diarrhea | 32% | 13.5% | 33.6% | 13.2% |
| Vomiting | 25.3% | 4.8% | 15.7% | 4.2% |
| Dysesthesia (skin sensations) | 12.5% | 0.9% | 7.3% | 0.7% |
| Stopped due to side effects | 11.3% | 4.9% | 7.7% | 4.9% |
Company-reported adverse events, not an FDA label table. INVESTIGATIONAL.
Source: Eli Lilly press releases, May 21 and June 6, 2026 (TRIUMPH-1) and Sept 29, 2026 (TRIUMPH-2) (checked on October 7, 2026)
Dysesthesia is the effect that drew the most attention. It means unusual skin sensations, such as tingling, burning or sensitivity to touch. It was reported in 12.5% of TRIUMPH-1 participants on 12 mg vs 0.9% on placebo, 7.3% vs 0.7% in TRIUMPH-2, and 20.9% vs 0.7% in TRIUMPH-4. Lilly says most cases were mild to moderate and resolved during treatment. A similar effect is listed on the label of the approved higher-dose Wegovy HD (22% on 7.2 mg vs 6% on 2.4 mg), but why it happens is not settled, and the FDA review of retatrutide will look at it closely.
Stopping because of side effects rose with dose in TRIUMPH-1 (4.1%, 6.9% and 11.3% vs 4.9% on placebo) and reached 18.2% on 12 mg in TRIUMPH-4. The Phase 2 trial, published in 2023, also showed a dose-dependent rise in heart rate that peaked around week 24. What is not known yet: safety beyond about two years, effects on heart attacks and strokes, rare side effects that only show up in very large groups, and which warnings an eventual label would carry. For the side effects of approved medicines in the same family, see our GLP-1 side effects guide.
What the results do not tell us yet
How it compares with tirzepatide. Only a head-to-head trial can say whether retatrutide leads to more weight loss than tirzepatide, the ingredient in Zepbound, and with what trade-offs. That trial, TRIUMPH-5, has not reported.
What the weight loss is made of. With any large weight loss, some of what is lost is lean mass, which includes muscle. The published abstracts we read do not give body-composition results for the Phase 3 trials, so we cannot say how much of the loss was fat. Our guide to muscle loss on GLP-1 medicines explains why strength training and protein matter on any of these drugs.
What happens after stopping, and long-term heart effects. A maintenance trial (TRIUMPH-6) and the outcomes trial are still running. With approved GLP-1 medicines, weight tends to come back when people stop, and there is no reason yet to expect retatrutide to be different.
Who it would be for, and what it would cost. Neither is known. A label, if the FDA approves one, would define who it is indicated for. There is no price, because it is not on the market.
What comes next
Retatrutide's road from here (as of October 7, 2026)
- TRIUMPH-5 resultsThe head-to-head trial against tirzepatide lists primary completion for November 2026 on ClinicalTrials.gov.
- Application to the FDALilly says it plans to submit in the first quarter of 2027 for obesity and related conditions.
- FDA reviewThe agency reviews benefits, risks and manufacturing; it can approve, ask for more data or decline.
- Label, if approvedAn official label would set who it is for, doses, warnings and side-effect tables.
- Longer-term answersTRIUMPH-6 (maintenance) and TRIUMPH-Outcomes (heart and kidney) run into 2028 and 2029.
A planned submission is not an approval, and FDA reviews often take many months. When something changes, it will appear in our monthly news roundup and on the emerging medications tracker, which also follows CagriSema, amylin-based drugs and other candidates. For a similar investigational story further along the road, see our CagriSema explainer.
Why not to buy “retatrutide” online
Strong headlines have led to products sold online as “retatrutide”, “reta” or “research peptides”, often labeled “not for human consumption”. Lilly states that retatrutide cannot be legally sold or marketed for human use. The FDA says retatrutide is not a component of any FDA-approved drug and cannot be used in compounding, and it has warned telehealth companies, ingredient distributors and outsourcing facilities over it. Products from these channels have no verified identity, purity, sterility or dose, and the trial results above say nothing about them. We do not link to sellers. Our page on compounded GLP-1s explains how the FDA treats copies of approved drugs, which is a different situation.
If you are interested in treatment now
Several FDA-approved medicines with strong evidence are available today, including weekly injections and daily pills. Our comparison of every FDA-approved weight-loss medication sets their label trials side by side, and our GLP-1 medications guide explains how the class works. If you would like to take part in research, you can search for recruiting studies on ClinicalTrials.gov; most retatrutide trials are no longer recruiting. Before any decision, our printable questions to ask before starting a GLP-1 can help you and your clinician talk through options, and the cost hub covers what approved medicines cost today.
Records in this article
Investigational: not FDA approvedPrescriptionInjectionRetatrutide: an investigational triple agonist (not FDA approved)Injection · Weekly
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- How do the approved medicines compare with what retatrutide has shown so far, for someone like me?
- Would waiting for a new medicine make sense, or should we consider an approved option now?
- Am I a candidate for a clinical trial, and what would taking part involve?
- How would we protect muscle and manage side effects on any strong weight-loss medicine?
Frequently asked questions
How much weight did people lose on retatrutide in Phase 3?
In TRIUMPH-1, adults with obesity lost on average 17.6%, 23.7% and 25.0% on 4, 9 and 12 mg over 80 weeks, vs 3.9% on placebo, counting everyone randomized. Lilly reported 28.3% on 12 mg if everyone had stayed on treatment. Averages do not predict individual results.
Is retatrutide FDA approved?
No. As of October 7, 2026, there is no FDA approval or label. Lilly says it plans to submit an application in the first quarter of 2027, and an FDA review usually takes many months after that.
Is retatrutide better than Zepbound?
Nobody knows yet. The trials so far compared retatrutide with placebo, not with tirzepatide (Zepbound). A head-to-head trial, TRIUMPH-5, lists primary completion for November 2026.
What is dysesthesia?
It means unusual skin sensations such as tingling, burning or sensitivity to touch. It was reported more often with retatrutide than placebo, more at higher doses; Lilly says most cases were mild to moderate and resolved during treatment.
Why do I see different numbers for the same trial?
Trials report two estimands. The treatment-regimen estimand counts everyone randomized, including those who stopped; the efficacy estimand estimates the result if everyone had stayed on the drug, so it is higher. Lilly releases use the efficacy estimand.
Can I get retatrutide now?
Only as a participant in a clinical trial. Products sold online as retatrutide or research peptides are not approved medicines, and the FDA says retatrutide cannot be used in compounding.
References
- Jastreboff AM, Kaplan LM, Davies MJ, et al.. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1). New England Journal of Medicine, 2026. doi:10.1056/NEJMoa2604169 · PMID 42814954 · NCT05929066 (accessed October 7, 2026) Randomized trial
- Bellido V, le Roux CW, Ekinci EI, et al.. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2). The Lancet, 2026. doi:10.1016/S0140-6736(26)01861-1 · PMID 42810372 · NCT05929079 (accessed October 7, 2026) Randomized trial
- Lilly’s triple agonist, retatrutide, delivered substantial weight loss and A1C reduction (BLA planned Q1 2027). Eli Lilly and Company (press release), 2026. (accessed October 7, 2026) News (reported facts only)
- Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline). Eli Lilly and Company (press release), 2026. (accessed October 7, 2026) News (reported facts only)
- Lilly’s triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea. Eli Lilly and Company (press release), 2026. (accessed October 7, 2026) News (reported facts only)
- Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3 topline). Eli Lilly and Company (press release), 2026. (accessed October 7, 2026) News (reported facts only)
- Lilly’s triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain (TRIUMPH-4 topline). Eli Lilly and Company (press release, via BioSpace), 2025. (accessed October 7, 2026) News (reported facts only)
- Jastreboff AM, Kaplan LM, Frias JP, et al.. Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. New England Journal of Medicine, 2023. doi:10.1056/NEJMoa2301972 · PMID 37366315 · NCT04881760 (accessed October 7, 2026) Randomized trial
- TRIUMPH-5: retatrutide compared with tirzepatide in adults with obesity (NCT06662383). ClinicalTrials.gov (NLM). NCT06662383 (accessed October 7, 2026) Government page
- ClinicalTrials.gov: TRIUMPH-Outcomes (cardiovascular and kidney outcomes with retatrutide). U.S. National Library of Medicine. NCT06383390 (accessed October 7, 2026) Government page
- FDA’s concerns with unapproved GLP-1 drugs used for weight loss. U.S. Food and Drug Administration, 2026. (accessed October 7, 2026) Government page
- Drugs@FDA: FDA-approved drugs (searched for cagrilintide; openFDA drugsfda dataset updated 2026-10-06). U.S. Food and Drug Administration. (accessed October 7, 2026) Government page
- Wilding JPH, Batterham RL, Calanna S, et al.. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine, 2021. doi:10.1056/NEJMoa2032183 · PMID 33567185 · NCT03548935 (accessed October 7, 2026) Randomized trial
- Jastreboff AM, Aronne LJ, Ahmad NN, et al.. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine, 2022. doi:10.1056/NEJMoa2206038 · PMID 35658024 · NCT04184622 (accessed October 7, 2026) Randomized trial
- WEGOVY (semaglutide) injection and tablets: prescribing information. Novo Nordisk, via DailyMed, 2026. (accessed October 7, 2026) Drug label
Facts checked on October 7, 2026
Educational information, not medical advice. Talk with a qualified healthcare professional about your own situation. In an emergency call 911.
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