Skip to content
Educational information only. Not medical advice. We sell nothing and take no affiliate money.
By /
Investigational peptide drugHuman trialsIn clinical trials

Retatrutide

Retatrutide

Last reviewed October 27, 2026 · 22 sources · Written for general readers · Compare with another compound →

The bottom line

Retatrutide is an experimental weekly shot from Eli Lilly that produced about 18% to 25% average weight loss in its main phase 3 trial. It is not approved anywhere, and Lilly plans to apply to FDA in early 2027, though some very sick patients can now ask for early access. Stomach side effects and odd skin sensations were common, and anything sold online now is unregulated.

Where the evidence stands

What it is

Retatrutide is an experimental weekly shot from Eli Lilly. It acts on three hormone receptors (GIP, GLP-1 and glucagon), so it is called a triple agonist.[1]

It is not approved for any use. Lilly says it plans to ask FDA for approval in the first quarter of 2027.[1] In August 2026 Lilly confirmed that doctors can request early access for some patients with hard to treat obesity who cannot join a trial.[2]

PubChem lists it under the code LY3437943 with CAS number 2381089-83-2.[3] Retatrutide sold online as a research chemical is not the drug tested in trials, and FDA says it cannot legally be used in compounding.[4]

Name
Retatrutide (Retatrutide)
Other names
LY3437943
Type
Investigational peptide drug
CAS number
2381089-83-2

What it does in the body

Retatrutide does not occur in nature. It is one lab made peptide built to switch on three receptors at once: the GLP-1 and GIP receptors, which respond to gut hormones released after meals, and the glucagon receptor, which responds to glucagon, a hormone made by the pancreas.[6][1]

This is the biology, area by area. A change measured in the body, like a higher blood level, does not always mean a person feels a benefit. The claims check below covers that.

Fat and appetite

Measured in people

In a 48 week trial of 338 adults with obesity, weight fell by up to 24.2% versus 2.1% on placebo.[7] In a body scan substudy of adults with type 2 diabetes, fat mass fell about 15% to 26% over 36 weeks on the middle and higher doses, versus about 4.5% on placebo. The share of weight lost as lean mass was similar to other obesity treatments.[8]

Energy use and metabolism

Seen in animals

In obese mice, the glucagon part of the drug raised the number of calories the body burned, so the mice lost more weight than eating less alone would explain.[6] We did not find a published human study that measured this.

Blood sugar

Measured in people

In TRANSCEND-T2D-1, 537 adults with type 2 diabetes took the weekly shot alone or placebo for 40 weeks. A1C, a three month blood sugar average, fell 1.69 to 1.94 points versus 0.81 on placebo, and no one had severe low blood sugar.[9] In a phase 2 trial of 281 adults, A1C fell by up to 2.02 points after 24 weeks versus almost no change on placebo.[10]

Liver

Measured in people

In a substudy of 98 adults with fatty liver disease, liver fat measured on scans fell by up to about 82% after 24 weeks, and up to 86% of people reached normal liver fat versus none on placebo.[11] This shows fat leaving the liver, but liver scarring and long term liver health were not measured.

Heart and blood vessels

Measured in people

A reanalysis of two phase 2 trials found apoB, a blood marker of artery clogging particles, fell about 21% to 24%, and hsCRP, a marker of inflammation, fell about 55% in people without diabetes.[12] Heart rate rose with dose and peaked around week 24.[7] In TRIUMPH-3, heart events in 1,949 adults with heart disease did not differ clearly from placebo.[1]

Joints

Measured in people

Within TRIUMPH-1, 574 adults had knee osteoarthritis. Knee pain scores fell 3.2 to 3.6 points on the drug versus 1.9 on placebo over 80 weeks.[13]

Skin and nerves

Measured in people

Dysesthesia, an odd skin feeling such as tingling, burning or sensitivity, was reported in 5% to 13% versus about 1% on placebo in TRIUMPH-1, and in 4% to 7% versus 1% in TRIUMPH-2.[14][15] The cause is not known, and most cases were mild to moderate.[14]

How it works

Retatrutide switches on three receptors that normally respond to gut and pancreas hormones.[1]

  • Two of its targets, GLP-1 and GIP, are the same as tirzepatide's. Activating them lowers appetite and food intake.[5]
  • Its third target is the glucagon receptor. In obese mice, this part raised the calories the body burned, adding to the weight loss from eating less.[6]
  • In lab tests it acted more strongly on the GIP receptor than on the GLP-1 and glucagon receptors.[6]

The receptor targets are well documented. How much each one adds in people is not yet clear.

What the research shows

We keep animal and human evidence apart. A result in animals is a reason to study something in people, not proof that it works in people.

Animal and lab studies

Animal work explains the design, but human trials matter more

  • In obese mice, retatrutide lowered body weight and improved blood sugar control.[6]
  • In mice, the glucagon part of the drug raised energy use, so weight loss was larger than from lower food intake alone.[6]
  • In lab cell tests, its action was balanced between the glucagon and GLP-1 receptors and stronger at the GIP receptor.[6]

Limit: Mouse results show how the drug was designed to work. Large human trials are the better guide to what it does in people.

Human studies

Large phase 3 trials show major weight loss, but it is still experimental

  • A first in human study found that a single shot lowered body weight for up to about six weeks, with side effects similar to other drugs of this type.[6]
  • A 48 week phase 2 trial in 338 adults with obesity found weight loss of up to 24.2% versus 2.1% on placebo. Stomach side effects were the most common and rose with dose, and heart rate went up, peaking at 24 weeks before easing.[7]
  • A phase 2 trial in 281 adults with type 2 diabetes found A1C fell by up to 2.02 points at 24 weeks, and weight fell by up to about 17% at 36 weeks versus 3% on placebo. Stomach side effects hit 35% of people on the drug, mostly mild to moderate.[10]
  • In a phase 2 substudy of 98 adults with fatty liver disease, up to 86% reached normal liver fat levels after 24 weeks, versus none on placebo.[11]
  • TRIUMPH-1 enrolled 2,339 adults with obesity or overweight and no diabetes for 80 weeks. Average weight loss was 17.6% to 25.0% depending on dose, versus 3.9% on placebo, and knee pain and sleep apnea also improved in the subgroups who had them.[13][14]
  • TRIUMPH-2, in 1,152 adults with type 2 diabetes and excess weight, found 11.9% to 18.8% weight loss versus 5.1% on placebo over 80 weeks, counting everyone who started. Diarrhea hit 27% to 34% versus 13%, nausea 14% to 28% versus 8%, and 84% finished treatment.[15] Lilly's earlier announcement, which estimated results for people who stayed on treatment, gave 12.7% to 20.8% versus 4.0%.[1]
  • TRANSCEND-T2D-1, in 537 adults with type 2 diabetes, found A1C fell 1.69 to 1.94 points versus 0.81 on placebo over 40 weeks, with 2% to 5% stopping for side effects versus none on placebo.[9]
  • TRIUMPH-3, in 1,949 adults with severe obesity and heart disease, found 21.6% to 22.6% weight loss versus 3.2% on placebo. The number of heart events did not differ clearly from placebo.[1]
  • TRIUMPH-4, in 445 adults with obesity and knee arthritis, found 26.4% to 28.7% weight loss over 68 weeks versus 2.1% on placebo, along with bigger drops in knee pain.[17]
  • Two trials in about 690 adults with obstructive sleep apnea found more weight loss and larger drops in breathing pauses than placebo over 80 weeks.[18]
  • A body scan substudy in adults with type 2 diabetes found fat mass fell about 15% to 26% on the middle and higher doses over 36 weeks, versus about 4.5% on placebo.[8]

Limit: Several results so far come from company announcements or reanalyses by company scientists, and safety beyond about two years is unknown.[1][12]

Claims check

The most common claims about this compound, and what studies actually found. Verdicts rate the evidence, not whether you should use it.

Causes very large weight loss

Shown in people

In TRIUMPH-1, 2,339 adults with obesity or overweight and no diabetes took a weekly shot or placebo for 80 weeks. Average weight loss was 17.6%, 23.7% and 25.0% across three doses, versus 3.9% on placebo.[13] Lilly reported that 45% of people on the highest dose who stayed on treatment lost 30% or more.[14] An earlier 48 week trial in 338 adults found up to 24.2% loss versus 2.1% on placebo.[7]

Lowers blood sugar in type 2 diabetes

Shown in people

In TRANSCEND-T2D-1, 537 adults with type 2 diabetes saw A1C fall 1.69 to 1.94 points over 40 weeks versus 0.81 on placebo, with weight loss of 11.5% to 15.3% versus 2.6%.[9] In TRIUMPH-2, 1,152 adults with type 2 diabetes and excess weight lost 11.9% to 18.8% over 80 weeks versus 5.1% on placebo, counting everyone who started.[15]

Works better than tirzepatide or semaglutide

Not tested

No published trial has compared retatrutide head to head with other weight loss drugs.[1][14] A 2026 review of 38 trials found placebo adjusted weight loss of about 22% for retatrutide, 19% for tirzepatide and 15% for semaglutide shots, but these trials enrolled different people, so the comparison is indirect.[16]

Clears liver fat

Mixed results

In a substudy of 98 adults with fatty liver disease, liver fat fell by up to about 82% after 24 weeks, and up to 86% of people reached normal liver fat versus none on placebo.[11] The study was small and measured fat on scans, not liver scarring or long term liver health. Larger liver trials are still running.[1]

Eases knee arthritis pain

Mixed results

In TRIUMPH-4, 445 adults with obesity and knee osteoarthritis took it or placebo for 68 weeks, and Lilly reported knee pain scores fell about 74% to 76% on the drug versus about 40% on placebo.[17] In the 574 TRIUMPH-1 participants with knee arthritis, pain scores fell 3.2 to 3.6 points versus 1.9 on placebo.[13] The benefit is real, but pain also improved a lot on placebo.

Protects the heart

Mixed results

In TRIUMPH-3, 1,949 adults with severe obesity and heart disease were followed for 80 weeks. Heart events were few, and their numbers did not differ clearly from placebo, while blood pressure, blood fats and an inflammation marker improved.[1]

Improves cholesterol and inflammation markers

Mixed results

A reanalysis of two phase 2 trials found non HDL cholesterol fell by up to 21% in one trial and 27% in the other, apoB by about 21% to 24%, and the inflammation marker hsCRP by about 55% in people without diabetes.[12] These are blood markers, not heart attacks or strokes, and the analysis was done after the trials by mostly Lilly authors.

Keeps muscle while you lose fat

Mixed results

In a body scan substudy of a phase 2 trial in adults with type 2 diabetes, most weight lost over 36 weeks was fat, and the share lost as lean mass was similar to other obesity treatments.[8] That means some lean mass is still lost, and strength was not measured.

The weight stays off after you stop

Not tested

Lilly's phase 3 results did not report what happens to weight after people stop.[14][1] Related drugs show large regain after stopping, but that has not been tested for retatrutide yet.

Known risks and side effects

  • Stomach and gut side effects are very common. In TRIUMPH-1, nausea hit 29% to 42% versus 15% on placebo, diarrhea 25% to 34% versus 14%, constipation 24% to 26% versus 11% and vomiting 11% to 25% versus 5%.[14] TRIUMPH-2 showed a similar pattern in people with diabetes.[15]
  • Odd skin sensations. Dysesthesia, an unpleasant or unusual feeling on the skin such as tingling or burning, was reported in 5% to 13% versus about 1% on placebo in TRIUMPH-1, and in up to 21% at the highest dose in TRIUMPH-4. Most cases were mild to moderate.[14][17]
  • More people quit at higher doses. In TRIUMPH-4, 12.2% to 18.2% stopped because of side effects versus 4.0% on placebo, and some people stopped because they felt they had lost too much weight.[17] In TRIUMPH-3 the figure was 9.8% to 13.5% versus 4.8%.[1] In TRIUMPH-2 it was 4% to 12% versus 5%.[15]
  • Low blood pressure, faster heart rate, and no official label. Low blood pressure was reported in 1% to 6% on the drug versus less than 1% on placebo in TRIUMPH-2.[15] Heart rate rose in the phase 2 trial.[7] Because it is not approved, there is no FDA label listing all known risks, and long term safety is still unknown.[1]
  • Unregulated research products and sports bans. FDA has warned sellers over retatrutide and says a research use only label does not make it legal to sell for human use.[4][19] A 2026 case report described a man with type 1 diabetes who became very ill with vomiting, diarrhea and dangerous ketone levels after injecting retatrutide bought online, though a gut infection was also present, so the drug's role could not be proven.[20] WADA bans at all times any drug without government approval for human use, and its 2027 list names peptides as an example.[21][22]

Regulatory status

Today: Retatrutide is investigational and not approved by FDA or any other agency. Lilly plans to file with FDA in the first quarter of 2027, runs an early access program for some patients who cannot join trials, and FDA says it cannot be used in compounding.[1][2][4]

  1. Lilly reported the first positive phase 3 results, from TRIUMPH-4 in knee arthritis.[17]
  2. FDA sent a warning letter to an online seller of retatrutide labeled research use only.[19]
  3. Lilly reported TRIUMPH-1 results in adults with obesity and no diabetes.[14]
  4. The first phase 3 diabetes trial, TRANSCEND-T2D-1, was published in The Lancet.[9]
  5. Lilly reported positive TRIUMPH-2 and TRIUMPH-3 results and said it plans to submit to FDA in the first quarter of 2027.[1]
  6. Lilly confirmed an early access program for some patients with hard to treat obesity who cannot enter a trial.[2]
  7. TRIUMPH-2 was published in The Lancet, and WADA's 2027 list added peptides as a named example of banned unapproved drugs.[15][22]
  8. FDA's updated GLP-1 page said retatrutide cannot be compounded and listed it among research only products it has warned about.[4]

Sources

  1. Eli Lilly and Company. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026. Company press release
  2. American Journal of Managed Care. Lilly expands retatrutide access amid doctor pushback. August 2026. News report
  3. National Center for Biotechnology Information. PubChem Substance Record for SID 474492335, Retatrutide. PubChem SID 474492335
  4. U.S. Food and Drug Administration. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. Content current as of October 1, 2026. FDA
  5. U.S. Food and Drug Administration. FDA Approves New Medication for Chronic Weight Management. November 8, 2023. FDA news release
  6. Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234-1247.e9. PMID 35985340
  7. 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. PMID 37366315
  8. Coskun T, Wu Q, Schloot NC, et al. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. Lancet Diabetes Endocrinol. 2025;13(8):674-684. PMID 40609566
  9. Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, 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. PMID 42250575
  10. Rosenstock J, Frias J, Jastreboff AM, 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
  11. Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037-2048. doi 10.1038/s41591-024-03018-2
  12. Ruotolo G, Harris C, Lin Y, et al. Retatrutide-Associated Improvements in Cardiovascular Risk Biomarkers in Adults With Obesity With or Without Type 2 Diabetes. Diabetes Obes Metab. 2026;28(11):10183-10194. PMID 42608321
  13. Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. 2026. PMID 42814954
  14. Eli Lilly and Company. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026. Company press release
  15. Bellido V, le Roux CW, Ekinci EI, 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. PMID 42810372
  16. Moiz A, Filion KB, Samuels AE, et al. Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes: An Updated Systematic Review. Ann Intern Med. 2026. PMID 42673585
  17. Eli Lilly and Company. 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. Company press release
  18. Grunstein RR, et al. Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea. N Engl J Med. 2026. doi 10.1056/NEJMoa2611477
  19. U.S. Food and Drug Administration. Warning letter 721806 to an online peptide seller. March 31, 2026. FDA warning letter
  20. Branine N. Online-Sourced Retatrutide Complicating Impending Diabetic Ketoacidosis in a Patient With Type 1 Diabetes and Concurrent Shigella Gastroenteritis. Cureus. 2026;18(8):e115260. PMID 42669023
  21. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 List
  22. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2027. Effective January 1, 2027. WADA 2027 List
Medical disclaimer

This page is educational information only. It is not medical advice and does not replace care from a licensed medical provider. Do not use this page to decide whether to take any substance. Talk to a licensed medical provider first.

Found an error or a newer study? We correct pages fast.

Report a correction →
Scroll to Top