Retatrutide: an investigational triple agonist (not FDA approved)

Key takeaways

• Retatrutide is investigational and not FDA approved for any use; the FDA says it cannot be used in compounding.^[1]
• In TRIUMPH-1, adults with obesity lost 25.0% of their weight on average at 80 weeks on 12 mg, vs 3.9% on placebo (treatment-regimen estimand).^[2]
• In adults with type 2 diabetes (TRIUMPH-2), average weight change was -18.8% on 12 mg vs -5.1% on placebo.^[3]
• Digestive side effects were the most common; dysesthesia and stopping due to side effects rose with dose.^[6]
• Lilly plans to submit retatrutide to the FDA in the first quarter of 2027; an FDA decision would follow review.^[9]

In short: Retatrutide is an investigational weekly injection from Eli Lilly that is not FDA approved for any use. It acts on three hormone receptors (GIP, GLP-1 and glucagon). In the Phase 3 TRIUMPH-1 trial, adults with obesity lost an average of 25.0% of their weight at 80 weeks on the highest dose, compared with 3.9% on placebo. Lilly says it plans to apply for U.S. approval in the first quarter of 2027. Until then, it is legally available only inside clinical trials (status checked on 2026-10-06).

This page explains what retatrutide is, how it is designed to work, what each published trial found (with the dates the results came out), the side effects reported so far, and what still has to happen before it could reach pharmacies. It is general education, not medical advice. If you are interested in new treatments, the safest steps are talking with a licensed clinician about approved options and, if you wish, looking for a trial on ClinicalTrials.gov.

What retatrutide is

Retatrutide (development code LY3437943) is a single molecule that activates the body’s receptors for three hormones: GIP (glucose-dependent insulinotropic polypeptide), GLP-1 (glucagon-like peptide-1) and glucagon. That is why it is often called a “triple agonist”. For comparison, semaglutide (Wegovy, Ozempic) acts on the GLP-1 receptor only, and tirzepatide (Zepbound, Mounjaro) acts on GIP and GLP-1 receptors. Our GLP-1 medications guide explains how the GLP-1 part reduces appetite and slows stomach emptying.

The new piece is glucagon. Glucagon is best known for raising blood sugar between meals, but it also acts on the liver and on energy use. Researchers are testing whether adding glucagon-receptor activity to GLP-1 and GIP activity increases energy expenditure and helps reduce liver fat; a 2026 review of the related drug survodutide describes this rationale. Whether the glucagon component adds benefits or risks in the long run is one of the questions the remaining trials are designed to answer.

Where it stands with the FDA

Retatrutide is in Phase 3, the last stage of testing before a company can apply for approval. In its July 23, 2026 announcement, Lilly said that with the TRIUMPH-2 and TRIUMPH-3 results it “now ha[s] the clinical data package to support global submissions” for obesity, knee osteoarthritis pain and obstructive sleep apnea, that it is completing the manufacturing data package required for a Biologics License Application, and that it plans to submit retatrutide for U.S. approval in the first quarter of 2027. Lilly repeated the Q1 2027 plan on September 29, 2026. A planned submission is not an approval: after submission, the FDA reviews the data, which usually takes many months, and may approve, ask for more information or decline. Our status badges guide explains why we label it INVESTIGATIONAL.

What the trials showed

Trial results are reported in two ways, and the difference matters. The treatment-regimen estimand counts everyone who was randomized, including people who stopped the drug; it is closer to what happens in real life. The efficacy estimand estimates the effect if everyone had kept taking it, so it gives bigger numbers. Company press releases often lead with the efficacy estimand. We show the treatment-regimen numbers from peer-reviewed papers where they exist, and label the others.

Phase 2 (NCT04881760, NEJM 2023). 338 adults with obesity, or overweight with a weight-related condition, received retatrutide at several doses or placebo for 48 weeks. Average weight change at 48 weeks was -24.2% with 12 mg and -2.1% with placebo; 83% of the 12 mg group lost at least 15%. Heart rate rose in a dose-dependent way, peaking at 24 weeks.

TRIUMPH-1 (NCT05929066, NEJM, published September 2026). 2,339 adults with obesity and without diabetes were randomized to 4 mg, 9 mg or 12 mg weekly or placebo for 80 weeks. Doses were reached step by step every four weeks starting from 2 mg. By the treatment-regimen estimand, weight changed by -17.6%, -23.7% and -25.0% with the three doses, compared with -3.9% with placebo. The trial also included people with knee osteoarthritis (574) and obstructive sleep apnea (243), and retatrutide reduced knee pain scores and breathing interruptions during sleep. By the efficacy estimand, Lilly reported -28.3% at 12 mg, and in a planned extension, people with a starting BMI of 35 or more who continued to 104 weeks reached -30.3%.

3.9%Placebo

17.6%Retatrutide 4 mg

23.7%Retatrutide 9 mg

25%Retatrutide 12 mg

TRIUMPH-1: average weight change at 80 weeks by dose (reductions shown as positive numbers)

Item	Value
Placebo	3.9%
Retatrutide 4 mg	17.6%
Retatrutide 9 mg	23.7%
Retatrutide 12 mg	25%

Treatment-regimen estimand (everyone randomized, including those who stopped). 2,339 adults with obesity, no diabetes. Investigational drug: not FDA approved.

Source: Jastreboff AM et al., New England Journal of Medicine 2026 (TRIUMPH-1) (checked on October 6, 2026)

TRIUMPH-2 (NCT05929079, The Lancet, published September 2026). 1,152 adults with type 2 diabetes and a BMI of 27 or more were followed for 80 weeks. By the treatment-regimen estimand, weight changed by -11.9% (4 mg), -16.8% (9 mg) and -18.8% (12 mg) vs -5.1% with placebo; 84% completed treatment. Lilly reported HbA1c reductions of up to 1.6 points from an average of 7.7%. As with other drugs, people with diabetes lost less weight on average.

TRIUMPH-3 (NCT05882045, topline results July 23, 2026). About 1,950 adults with severe obesity (BMI of 35 or more) and established cardiovascular disease, with or without diabetes, took 9 mg or 12 mg or placebo. Lilly reported weight changes of -21.6% and -22.6% vs -3.2% (efficacy estimand). The trial was not designed to prove heart protection: major cardiovascular events were fewer than expected in all groups, and the hazard ratio for heart attack, stroke or cardiovascular death was 1.12 (95% confidence interval 0.64 to 1.96), which means the trial could not show a difference either way. A separate 10,000-person outcomes trial (TRIUMPH-Outcomes, NCT06383390) is under way, with primary completion listed for 2029.

TRIUMPH-4 (NCT05931367, topline results December 11, 2025). 445 adults with obesity or overweight and knee osteoarthritis took 9 mg, 12 mg or placebo for 68 weeks. Lilly reported treatment-regimen weight changes of -20.0% and -23.7% vs -4.6% with placebo, and knee pain scores (WOMAC) that improved by up to 75.8% vs 40.3% on placebo.

TRANSCEND-T2D-1 (NCT06354660, The Lancet, June 2026). In 537 adults with type 2 diabetes not controlled by diet and exercise, HbA1c fell by 1.69 to 1.94 points with retatrutide vs 0.81 with placebo over 40 weeks.

• Retatrutide 12 mg
• Placebo

Phase 2, 48 weeks24.2%2.1%

TRIUMPH-1, 80 weeks25%3.9%

TRIUMPH-4 (knee OA), 68 weeks23.7%4.6%

TRIUMPH-2 (type 2 diabetes), 80 weeks18.8%5.1%

Highest dose (12 mg) vs placebo across trials: average weight change (reductions shown as positive numbers)

Item	Retatrutide 12 mg	Placebo
Phase 2, 48 weeks	24.2%	2.1%
TRIUMPH-1, 80 weeks	25%	3.9%
TRIUMPH-4 (knee OA), 68 weeks	23.7%	4.6%
TRIUMPH-2 (type 2 diabetes), 80 weeks	18.8%	5.1%

Phase 2 is a least-squares mean; the others are treatment-regimen estimands. TRIUMPH-4 is not yet peer reviewed. Different trials: compare with care.

Source: NEJM 2023 (Phase 2), NEJM 2026 (TRIUMPH-1), The Lancet 2026 (TRIUMPH-2), Eli Lilly press release Dec 11, 2025 (TRIUMPH-4) (checked on October 6, 2026)

Side effects reported so far

There is no FDA label yet, so the only safety information comes from trial reports. As with other incretin medicines, digestive side effects were the most common and rose with the dose. In TRIUMPH-1, Lilly reported nausea in 28.6%, 38.4% and 42.4% of people on 4, 9 and 12 mg vs 14.8% on placebo; diarrhea in 25.2% to 34.1% vs 13.5%; constipation in 23.8% to 26.1% vs 10.9%; and vomiting in 10.6% to 25.3% vs 4.8%.

• Retatrutide 12 mg
• Placebo

Nausea42.4%14.8%

Diarrhea32%13.5%

Constipation26.1%10.9%

Vomiting25.3%4.8%

Upper respiratory infection13.1%11.6%

Dysesthesia (skin sensations)12.5%0.9%

Urinary tract infection8.4%5.3%

Stopped due to side effects11.3%4.9%

TRIUMPH-1: side effects at the highest dose (12 mg) vs placebo

Item	Retatrutide 12 mg	Placebo
Nausea	42.4%	14.8%
Diarrhea	32%	13.5%
Constipation	26.1%	10.9%
Vomiting	25.3%	4.8%
Upper respiratory infection	13.1%	11.6%
Dysesthesia (skin sensations)	12.5%	0.9%
Urinary tract infection	8.4%	5.3%
Stopped due to side effects	11.3%	4.9%

Company-reported adverse events, not an FDA label table. Investigational drug.

Source: Eli Lilly press releases, May 21 and June 6, 2026 (TRIUMPH-1) (checked on October 6, 2026)

Two signals deserve attention. Dysesthesia, meaning unusual skin sensations such as tingling, burning or sensitivity, was reported in 5.1% to 12.5% of TRIUMPH-1 participants vs 0.9% on placebo, and in 20.9% of the 12 mg group in TRIUMPH-4 vs 0.7% on placebo; Lilly says most cases were mild to moderate and resolved during treatment. Stopping because of side effects rose with dose: 4.1%, 6.9% and 11.3% in TRIUMPH-1 (vs 4.9% placebo), and 18.2% on 12 mg in TRIUMPH-4 (vs 4.0%), where Lilly reported lower rates among people with a starting BMI of 35 or more. Urinary tract infections were slightly more frequent than with placebo. Heart rate increases were seen in the Phase 2 trial.

What is not known yet: long-term safety beyond about two years, effects on heart attacks and strokes (the outcomes trial is ongoing), rare side effects that only appear in very large populations, and whether retatrutide will carry the same thyroid C-cell tumor boxed warning that approved GLP-1 medicines have. Those answers will come from the FDA review and, if approved, the official label. For the side effects of approved medicines in the same family, see our GLP-1 side effects guide.

Who has been studied, and who has not

The obesity trials enrolled adults with obesity, or with overweight and at least one weight-related condition, with separate trials for people with type 2 diabetes, cardiovascular disease, knee osteoarthritis and sleep apnea. Trials of this kind usually exclude people who are pregnant or breastfeeding, so there is no safety information for pregnancy. No results in children have been reported. Because it is not approved, there is no official list of who should not use it, no official dosing and no official interaction guidance.

Trials still running

Trial	Question	Status on ClinicalTrials.gov (checked 2026-10-06)
TRIUMPH-5 (NCT06662383)	Retatrutide compared head to head with tirzepatide in adults with obesity	Active, not recruiting; primary completion listed November 2026
TRIUMPH-6 (NCT06859268)	Maintenance of weight reduction	Active, not recruiting; primary completion listed April 2028
TRIUMPH-7 (NCT07035093)	Obesity or overweight with chronic low back pain	Active, not recruiting; primary completion listed September 2027
TRIUMPH-8 (NCT07232719)	Obesity or overweight	Active, not recruiting; primary completion listed July 2027
TRIUMPH-9 (NCT07357415)	Obesity or overweight without type 2 diabetes	Active, not recruiting; primary completion listed October 2028
TRIUMPH-Outcomes (NCT06383390)	Cardiovascular and kidney outcomes in about 10,000 adults with obesity	Active, not recruiting; primary completion listed February 2029

Gray-market “retatrutide”: why it is risky

Because the trial results drew wide attention, products labeled “retatrutide” are sold online, often as “research chemicals not for human use”. Lilly states that retatrutide is an investigational molecule that “cannot be legally sold or marketed for human use”. The FDA states that retatrutide cannot be used in compounding under federal law, is not a component of any FDA-approved drug, and has not been found safe and effective for any condition; it has warned telehealth companies for marketing it, ingredient distributors for selling it to compounders, and outsourcing facilities for repackaging it. Products from these channels have no verified identity, purity, sterility or dose, and side effects cannot be traced or treated with any confidence. We do not link to sellers. If you have used such a product and feel unwell, contact a clinician; you can report problems to the FDA’s MedWatch program at 1-800-FDA-1088.

Cost and access

Retatrutide has no price because it is not on the market; any price you see is for an unapproved product. The legal way to get it today is to join a clinical trial, where the study drug is provided under a research protocol with medical monitoring. You can search for recruiting studies on ClinicalTrials.gov (most current retatrutide trials are no longer recruiting) and discuss eligibility with your clinician. For approved medicines today, see our cost hub and the GLP-1 cost comparison tool.

Approved options today

Several medicines with strong evidence are FDA approved for weight management now, including Zepbound (tirzepatide), Wegovy and the higher-dose Wegovy HD (semaglutide), and the daily pill Foundayo (orforglipron). Our medications hub lists them with their status badges, the semaglutide vs tirzepatide page compares the two leading molecules, and our emerging medications tracker follows retatrutide and the other drugs in development.

What studies showed

Trial	Population	Duration	Outcome as reported
Phase 2 obesity trial NCT04881760	338 adults with obesity, or overweight with a weight-related condition	48 weeks	Weight change -24.2% (12 mg) vs -2.1% placebo at 48 weeks.[5]
TRIUMPH-1 NCT05929066	2,339 adults with obesity without diabetes (with knee OA and OSA substudies)	80 weeks	Treatment-regimen estimand: -17.6% (4 mg), -23.7% (9 mg), -25.0% (12 mg) vs -3.9% placebo.[2]
TRIUMPH-2 NCT05929079	1,152 adults with type 2 diabetes and BMI 27+	80 weeks	Treatment-regimen estimand: -11.9%, -16.8%, -18.8% vs -5.1% placebo.[3]
TRIUMPH-3 (topline) NCT05882045	About 1,950 adults with BMI 35+ and established cardiovascular disease	80 weeks	Efficacy estimand (company-reported): -21.6% (9 mg), -22.6% (12 mg) vs -3.2% placebo; MACE-3 HR 1.12 (95% CI 0.64-1.96).[8]
TRIUMPH-4 (topline) NCT05931367	445 adults with obesity or overweight and knee osteoarthritis	68 weeks	Treatment-regimen estimand (company-reported): -20.0% (9 mg), -23.7% (12 mg) vs -4.6% placebo.[10]
TRANSCEND-T2D-1 NCT06354660	537 adults with type 2 diabetes on diet and exercise alone	40 weeks	HbA1c -1.69% to -1.94% vs -0.81% placebo.[4]

Average results from trials; individual results vary. Results from different trials cannot be compared directly.

Side effects

Common side effect	How often (label)
Nausea	TRIUMPH-1 (company-reported): 28.6% / 38.4% / 42.4% (4/9/12 mg) vs 14.8% placebo
Diarrhea	25.2% / 34.1% / 32.0% vs 13.5%
Constipation	23.8% / 25.9% / 26.1% vs 10.9%
Vomiting	10.6% / 22.8% / 25.3% vs 4.8%
Dysesthesia	5.1% / 12.3% / 12.5% vs 0.9% (TRIUMPH-1); 20.9% on 12 mg in TRIUMPH-4
Urinary tract infection	7.5% / 8.8% / 8.4% vs 5.3%

Serious risks

• No FDA label: serious risks are not yet officially characterized
• Discontinuation due to adverse events rose with dose (up to 11.3% in TRIUMPH-1 and 18.2% in TRIUMPH-4 at 12 mg)
• Dose-dependent heart rate increase seen in the Phase 2 trial
• Cardiovascular outcomes not yet established (TRIUMPH-Outcomes ongoing)
• Gray-market products: unknown identity, purity, sterility and dose

Stopping and keeping results

Trials show that weight often returns after these medicines are stopped. Plan any change with your prescriber. Stopping a GLP-1: what trials show and how people keep results

Questions to ask your doctor or pharmacist

• Which FDA-approved options fit my situation today while new drugs are still being studied?
• Would a clinical trial make sense for me, and how do I judge one?
• If retatrutide is approved, what would make me a good or poor candidate?
• What are the risks of products sold online as research peptides?
• How would we protect muscle and plan for maintenance with any of these medicines?

Frequently asked questions

Is retatrutide FDA approved?

No. As of October 6, 2026, retatrutide is investigational and not approved for any use. Lilly says it plans to submit an application to the FDA in the first quarter of 2027.

When could retatrutide be available?

Only after the FDA reviews and approves an application. Lilly plans to submit in Q1 2027; FDA reviews usually take many months, and approval is not guaranteed. Any earlier date you see online is speculation.

How much weight did people lose on retatrutide?

In TRIUMPH-1, average weight change at 80 weeks was -17.6%, -23.7% and -25.0% on 4, 9 and 12 mg vs -3.9% on placebo, counting everyone randomized. Lilly also reported -28.3% on 12 mg if everyone had stayed on treatment.

How is retatrutide different from Zepbound and Wegovy?

Wegovy (semaglutide) acts on GLP-1 receptors; Zepbound (tirzepatide) on GIP and GLP-1 receptors; retatrutide adds glucagon receptors as well. A head-to-head trial against tirzepatide (TRIUMPH-5) is ongoing.

Can I buy retatrutide online?

Not legally. Lilly says it cannot be legally sold or marketed for human use, and the FDA has warned companies that marketed or sold it. Products sold as research peptides have unknown contents and doses. The only legal access is through a clinical trial.

Can a compounding pharmacy make retatrutide?

No. The FDA states that retatrutide cannot be used in compounding under federal law.

What side effects has retatrutide caused?

Mostly nausea, diarrhea, constipation and vomiting, especially at higher doses. Dysesthesia (unusual skin sensations) and urinary tract infections were more frequent than with placebo, and more people stopped treatment because of side effects at 12 mg.

Does retatrutide protect the heart?

Not shown. In TRIUMPH-3, the trial could not show a difference in heart attack, stroke or cardiovascular death (hazard ratio 1.12, wide confidence interval). A dedicated 10,000-person outcomes trial is running until about 2029.

How can I join a retatrutide trial?

Search ClinicalTrials.gov for retatrutide and check which studies are recruiting, then discuss eligibility with your clinician. Most current retatrutide trials are no longer recruiting.

Official sources

• Manufacturer information
• Status source

References

1. 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
2. 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
3. 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
4. Bajaj HS, Welch M, Shah P, et al.. Efficacy and safety of retatrutide in people with type 2 diabetes (TRANSCEND-T2D-1): a phase 3 trial. The Lancet, 2026. doi:10.1016/S0140-6736(26)00967-0 · PMID 42250575 · NCT06354660 (accessed October 6, 2026) Randomized trial
5. 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
6. 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)
7. 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)
8. 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)
9. 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)
10. 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)
11. ClinicalTrials.gov: TRIUMPH program records (NCT05929066 and related studies). U.S. National Library of Medicine. (accessed October 6, 2026) Government page
12. Sergi CM.. Survodutide for the treatment of obesity: mechanistic rationale, clinical evidence, and remaining uncertainties. Contemporary Clinical Trials, 2026. doi:10.1016/j.cct.2026.108493 · PMID 42822760 (accessed October 6, 2026) Review

Facts checked on October 6, 2026

Educational information, not medical advice. Talk with a qualified healthcare professional about your own situation. In an emergency call 911.