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GIP, GLP-1 and glucagon receptor agonist

Retatrutide

Retatrutide is an investigational once-weekly Eli Lilly injection that acts on GIP, GLP-1 and glucagon receptors, in phase 3 trials for obesity and diabetes.

Medical review in progressLast reviewed

US regulatory status

Investigational, not approved

Retatrutide is not approved by the FDA for any use and has no brand name. Eli Lilly published phase 3 trials in 2026, but no FDA filing or approval had been announced as of October 16, 2026. The FDA says retatrutide cannot be used in compounding, and it has warned telehealth companies, ingredient distributors and websites selling “research use only” retatrutide.

As of

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On this page
  1. US regulatory status
  2. At a glance
  3. What the research shows
  4. Side effects and safety
  5. Vial math
  6. Questions people ask
  7. Sources
  8. Related compounds

At a glance

Also known as
LY3437943
Supplied as
Freeze-dried powder, mixed before use
Research
Limited human evidence
US status
US status: Investigationalchecked

What the research shows

Evidence grade

Limited human evidence

Some studies in people, but they are small, short, early-phase or uncontrolled.

Phase 3 trials have been published, but the FDA has not reviewed them. In TRIUMPH-1 (2,339 adults with obesity but not diabetes, 80 weeks), average weight change was −17.6% to −25.0% across the three doses tested, compared with −3.9% on placebo. In the subgroup with knee osteoarthritis, the WOMAC pain score fell by 3.2 to 3.6 points, compared with 1.9 on placebo; in the subgroup with sleep apnea, breathing events during sleep fell by 22.8 to 34.3 per hour, compared with 9.6 on placebo. In TRIUMPH-2 (1,152 adults with obesity and type 2 diabetes, 80 weeks), weight change was −11.9% to −18.8%, compared with −5.1% on placebo. In TRANSCEND-T2D-1 (537 adults with type 2 diabetes managed with diet and exercise, 40 weeks), HbA1c fell by 1.69 to 1.94 percentage points, compared with 0.81 on placebo, and weight by 11.5% to 15.3%, compared with 2.6%. In a phase 2a study of 98 people with fatty liver disease (MASLD), liver fat fell by 42.9% to 82.4% in 24 weeks, and up to 86% reached a normal liver-fat level, compared with none on placebo. Lilly reported in July 2026 that in TRIUMPH-3 (1,949 adults with severe obesity and heart disease, 80 weeks), weight loss was 21.6% and 22.6% on the two doses tested, compared with 3.2% on placebo; these figures are not yet peer reviewed. Head-to-head trials against tirzepatide (TRIUMPH-5) and semaglutide (TRANSCEND-T2D-2) had not reported yet. Eli Lilly funded all of these trials.

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How we grade evidence

  1. Strong human evidence

    Consistent results from large randomized controlled trials in people.

  2. Limited human evidence · this page

    Some studies in people, but they are small, short, early-phase or uncontrolled.

  3. Mixed evidence

    Studies in people disagree, or strong evidence for one use sits beside weak evidence for another.

  4. Animal or lab studies only

    Studied in cells or animals, not properly in people. Animal results may not apply to humans.

The grade describes how much research exists and in whom. It is not a judgment that a compound works or is safe.

Side effects and safety

Retatrutide has no FDA label, so there is no official list of warnings for it. In trials, the most common side effects were digestive, and they rose with dose. In TRIUMPH-2, diarrhea affected 27% to 34% of people across the doses tested (13% on placebo) and nausea 14% to 28% (8% on placebo). Dysesthesia, an unusual skin sensation, affected 4% to 7% (1% on placebo), and low blood pressure 1% to 6% (under 1% on placebo). Depending on the dose, 4% to 12% stopped treatment for good because of adverse events or death, compared with 5% on placebo; investigators judged all deaths unrelated to the study treatment. In the phase 2 trial, heart rate rose with dose, peaked at 24 weeks and declined after that. Trials lasted up to 80 weeks, so longer-term effects are unknown. Retatrutide sold outside trials is an unapproved drug: the FDA urges people not to buy products labeled “for research purposes”, which are of unknown quality and may be harmful.

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Vial math

Pre-filled calculators turn your vial, water and prescribed dose into syringe units.

Pre-filled for your vial size

These pages do the arithmetic for a vial you already have. They don’t suggest a dose.

This is arithmetic, not medical advice. Confirm with your prescriber or pharmacist.

Questions people ask

Is retatrutide FDA-approved?

No. As of October 16, 2026, retatrutide has no FDA approval, no brand name and no approved use. In July 2026, Eli Lilly said it was completing the manufacturing data required for a Biologics License Application and planned to submit retatrutide for US approval in the first quarter of 2027; we found no filing announced since. The FDA says retatrutide cannot be used in compounding, so any “compounded” or “research” retatrutide is an unapproved drug.

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What are the side effects of retatrutide?

Mostly digestive, chiefly diarrhea and nausea, more often at higher doses. In the TRIUMPH-2 trial, diarrhea affected 27% to 34% of people on retatrutide (13% on placebo) and nausea 14% to 28% (8% on placebo). Retatrutide also caused more dysesthesia (unusual skin sensations) and low blood pressure than placebo, and in the phase 2 trial heart rate rose before easing after week 24. The trials lasted up to 80 weeks, so long-term side effects are not known.

Sources

Does retatrutide cause skin sensitivity?

Trials reported it. The medical term is dysesthesia: tingling or unusual sensations in the skin. In TRIUMPH-2 it affected 4% to 7% of people on retatrutide, compared with 1% on placebo. In TRIUMPH-3, Lilly reported it in 6.4% of people on each dose tested, compared with 1.3% on placebo, and said the events were generally mild to moderate and most resolved during treatment. The TRIUMPH-3 figures come from the company and are not yet peer reviewed.

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How does retatrutide compare with tirzepatide?

No trial has published a direct comparison yet. TRIUMPH-5, a phase 3 trial of about 800 adults with obesity, tests retatrutide against tirzepatide over 80 weeks; as of October 2026 it was active but no longer recruiting, with primary completion expected in November 2026 and nothing reported yet. Tirzepatide acts on GIP and GLP-1 receptors and is FDA-approved as Mounjaro and Zepbound; retatrutide adds glucagon-receptor activity and is unapproved. Figures from separate trials are not a fair comparison, because the people, trial length and methods differ.

Sources

Is retatrutide a “GLP-3”?

No. There is no hormone called GLP-3. The label is used informally because retatrutide acts on three receptors: GIP, GLP-1 and glucagon. Tirzepatide acts on two (GIP and GLP-1), and semaglutide on one (GLP-1).

Source

What is the half-life of retatrutide?

About 6 days, measured in an early (phase 1b) study in people with type 2 diabetes. The researchers said this suits once-weekly injection.

Source

Sources

  1. Novel Drug Approvals for 2026U.S. Food and Drug Administration, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  2. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of ObesityN Engl J Med, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  3. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trialLancet, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  4. A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight (TRIUMPH-1), NCT05929066ClinicalTrials.gov, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  5. FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight LossU.S. Food and Drug Administration, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  6. Warning letter: Gram Peptides (MARCS-CMS 721806)U.S. Food and Drug Administration, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  7. Warning letter: TXP Innovations LLC dba Tex Peptides (MARCS-CMS 735067)U.S. Food and Drug Administration, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  8. 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 trialLancet, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  9. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trialNat Med, 2024 · Accessed Oct 16, 2026 (opens in a new tab)
  10. Lilly’s triple agonist retatrutide successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1CEli Lilly and Company (press release via BioSpace), 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  11. A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Retatrutide Compared to Tirzepatide in Adults Who Have Obesity (TRIUMPH-5), NCT06662383ClinicalTrials.gov, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  12. Retatrutide Once Weekly Compared With Semaglutide Once Weekly in Adult Participants With Type 2 Diabetes (TRANSCEND-T2D-2), NCT06260722ClinicalTrials.gov, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  13. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 TrialN Engl J Med, 2023 · Accessed Oct 16, 2026 (opens in a new tab)
  14. ZEPBOUND (tirzepatide) injection, prescribing informationDailyMed, U.S. National Library of Medicine, 2026 · Accessed Oct 16, 2026 (opens in a new tab)
  15. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trialLancet, 2022 · Accessed Oct 16, 2026 (opens in a new tab)

Related compounds

Guides

Medical review in progressLast reviewed

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