Peptide Graded

All peptides / Gut and weight

Retatrutide

Triple GLP-1 / GIP / glucagon agonist

Also LY3437943, LY-3437943, LY 3437943, Reta, Triple G, GGG tri-agonist

Evidence
BSome human evidence
FDA status
In clinical trialsas of 2026-10-26
Route
Injection
Studies cited
4 human0 animal or cell

A weekly weight-loss injection not yet approved. In trials people lost up to about a quarter of their body weight in 48 weeks.

Sold for

Retatrutide is talked about as the next step beyond tirzepatide, a triple-hormone injection that produced the largest weight loss yet seen in a drug trial.

Studies say

Randomized trials show about a quarter of body weight lost over 48 weeks and roughly a fifth over 80 weeks in people with diabetes, with gastrointestinal side effects and heart rate increases, which supports a B pending approval and full phase 3 publication.

Why grade B. There is one published randomized phase 2 trial in obesity (338 adults, 48 weeks), a 98-person liver fat substudy of that trial, and one published phase 3 trial, TRIUMPH-2, in 1,152 adults with obesity and type 2 diabetes over 80 weeks; other phase 3 results exist only as press releases. Multiple randomized trials point the same way, but the drug is not approved, most of the roughly 5,800-person TRIUMPH program is unpublished, and there is no long-term safety data, so the grade is B and not A. 2347

FDA. Retatrutide is an investigational drug and is not approved by the FDA for any use. Eli Lilly has said it plans to file for approval in the first quarter of 2027 after completing manufacturing data. Vials sold online as retatrutide are not a legal product; the FDA has stated that unapproved GLP-1 class drugs cannot be used in compounding. 56

Written from 9 cited sources. Last refreshed 2026-10-27. Not physician reviewed.

What this means for you

What people take it for
Losing weight.
Can a US doctor prescribe it?
Not yet; it is still in trials. Vials sold online are not legal products.
Properly tested in people?
Partly: some human trials, with gaps: a 338-adult trial, with larger trials not yet fully published.

Evidence checklist

  • Randomised controlled trial Phase 2 and TRIUMPH-2 placebo-controlledyes
  • Human study over 100 people Phase 2: 338; TRIUMPH-2: 1,152yes
  • More than one research group All trials by Eli Lillyno
  • Clinical outcomes, not surrogate markers Weight and liver fat, not clinical outcomesno
  • Human safety data beyond case reports Trial data; no long-term safetyyes

Drawn from the cited studies below. A dash means the sources give no information.

What it is

Retatrutide (LY3437943) is a single lab-made peptide, engineered by Eli Lilly to activate three hormone receptors at once: GLP-1, GIP and glucagon. Semaglutide hits one of these (GLP-1). Tirzepatide hits two (GLP-1 and GIP). Retatrutide adds glucagon. It is a weekly injection under the skin. It is built on a modified GIP backbone with a fatty acid chain that keeps it in the body longer. 12

The phase 3 program is called TRIUMPH. It is a set of four randomized, placebo-controlled trials in more than 5,800 adults. They test retatrutide for weight management. Inside the same trials, they also test it for obstructive sleep apnea and knee osteoarthritis. TRIUMPH-2 was published in The Lancet in 2026. TRIUMPH-3, in people with cardiovascular disease, has reported topline results. 47

How it works

GLP-1 receptor activation slows stomach emptying and increases insulin release when glucose is high. It also reduces appetite through the brainstem and hypothalamus. GIP receptor activation adds to the insulin effect. Together with GLP-1, it seems to reduce the nausea that GLP-1 drugs cause on their own. The glucagon part is the unusual one. Glucagon normally raises blood glucose. But it also increases energy use and drives the liver to burn fat. The bet is that the GLP-1 and GIP actions cancel the glucose rise. The glucagon action then adds calorie burning and liver fat clearance on top of lower intake. The liver fat substudy is the clearest sign that the glucagon arm is doing something. In it, retatrutide cleared more than 80 percent of liver fat at the higher doses. 13

What human research shows

The phase 2 obesity trial randomized 338 adults without diabetes. They got one of four retatrutide doses or placebo for 48 weeks. Mean weight loss at 48 weeks was 8.7 percent at the lowest dose. It was 17.1 percent at the next, 22.8 percent at the next, and 24.2 percent at the highest. Placebo lost 2.1 percent. At the two higher doses, every participant lost at least 5 percent. More than 80 percent lost at least 15 percent. Weight was still falling at 48 weeks and had not leveled off. 2

A substudy of that trial had 98 participants with fatty liver disease. At 24 weeks, liver fat fell by 43 to 82 percent across the dose range, versus no change on placebo. By then, 86 percent of those on the highest dose had normal liver fat. 3

TRIUMPH-2 randomized 1,152 adults with obesity and type 2 diabetes. They got three retatrutide doses or placebo for 80 weeks. Mean weight loss ranged from 12.7 to 20.8 percent across doses. HbA1c fell by up to 1.6 percentage points. Participants with a starting BMI of 35 or more on the highest dose lost an average of 23.4 percent. Stopping because of side effects was 3.8 to 11.6 percent on retatrutide versus 4.9 percent on placebo. 47

StudyModelFinding
Phase 2 obesity trialHumans, n=338, randomized, double-blind, placebo-controlled, 48 weeksUp to 24.2 percent mean weight loss versus 2.1 percent on placebo, with dose-related gastrointestinal effects and heart rate increases. 2
Liver fat substudyHumans, n=98 with fatty liver disease, randomized, placebo-controlled, 48 weeksLiver fat fell up to 82 percent at 24 weeks and most participants on higher doses reached normal liver fat. 3
TRIUMPH-2Humans, n=1,152 with obesity and type 2 diabetes, randomized, double-blind, placebo-controlled, 80 weeks12.7 to 20.8 percent mean weight loss across doses and HbA1c reductions of up to 1.6 points. 4
TRIUMPH program designFour phase 3 trials, more than 5,800 participants, basket designTests weight management with nested sleep apnea and knee osteoarthritis endpoints and a separate cardiovascular disease trial. 7

Safety

Gut effects were the most common side effects in every trial. These were nausea, diarrhea, vomiting and constipation. They were dose-related, and a lower starting dose reduced them. Heart rate rose with the dose. It peaked around 24 weeks at a few beats per minute above placebo and then declined. Other GLP-1 drugs do this too. But the glucagon part makes it a point to watch. In TRIUMPH-2, one in nine participants on the middle dose stopped because of side effects. There is no safety data beyond 80 weeks. There is none from unsupervised use of unregulated product. 247

Questions for your clinician

  • Is retatrutide approved, and are the vials sold online the real product?
  • How do approved drugs like semaglutide or tirzepatide compare for me?
  • What does the heart rate increase mean given my heart history?

Questions people ask

When might the FDA decide on retatrutide?

No. As of October 2026 it is still in phase 3 trials. Lilly has said it plans to submit an application in early 2027. So a decision would come no sooner than late 2027. 5

How does retatrutide go beyond tirzepatide?

Tirzepatide activates the GLP-1 and GIP receptors. Retatrutide activates those two plus the glucagon receptor. This is thought to raise energy use and clear fat from the liver. In its phase 2 trial, weight loss at 48 weeks was larger than tirzepatide gave at 72 weeks in its own phase 3 trial. But the two have not been compared head to head. 12

What weight loss did retatrutide produce in trials?

Up to 24.2 percent of body weight at 48 weeks in adults with obesity and no diabetes. Up to 20.8 percent at 80 weeks in adults with obesity and type 2 diabetes, who tend to lose less on this class of drugs. Placebo groups lost about 2 percent. 24

Can you get retatrutide without joining a trial?

Not legally in the United States. It is not approved, and the FDA has said unapproved GLP-1 class drugs cannot be compounded. Products sold online as retatrutide have no verified identity, purity or dose. Trial enrollment is listed on ClinicalTrials.gov. 69

What side effects has it shown?

Mostly nausea, vomiting, diarrhea and constipation. These were dose-related and eased with a lower starting dose. Heart rate rose by a few beats per minute in a dose-dependent way and then settled. Between 4 and 12 percent of participants in TRIUMPH-2 stopped because of side effects, against 5 percent on placebo. 24

Citations

  1. StatPearls: GLP-1 receptor agonists ncbi.nlm.nih.gov
  2. Jastreboff 2023, N Engl J Med: triple-hormone-receptor agonist retatrutide for obesity, phase 2 trial pubmed.ncbi.nlm.nih.gov
  3. Sanyal 2024, Nat Med: retatrutide for metabolic dysfunction-associated steatotic liver disease, phase 2a substudy pubmed.ncbi.nlm.nih.gov
  4. Lancet 2026: TRIUMPH-2, retatrutide in adults with obesity and type 2 diabetes doi.org
  5. Eli Lilly Q2 2026 earnings release (SEC filing): retatrutide filing plans sec.gov
  6. FDA: concerns with unapproved GLP-1 drugs used for weight loss fda.gov
  7. Diabetes Obes Metab 2026: rationale and design of the TRIUMPH registrational trials pubmed.ncbi.nlm.nih.gov
  8. Eli Lilly press release, July 2026: TRIUMPH-2 and TRIUMPH-3 topline results biospace.com
  9. ClinicalTrials.gov: retatrutide trial listings clinicaltrials.gov

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