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Retatrutide

GIP, GLP-1 and glucagon receptor triple agonist

Status

In clinical trials

Not approved anywhere; Eli Lilly says its phase 3 data package now supports registrations for obesity, obstructive sleep apnea and knee osteoarthritis pain, with a US application planned for the first quarter of 2027.

Evidence

Moderate

Peer-reviewed phase 2 trials and one published phase 3 trial (TRANSCEND-T2D-1) are positive, but the pivotal obesity results (TRIUMPH program) are so far mainly company-reported.

In sport

WADAProhibited (WADA)

Retatrutide is an investigational once-weekly injected peptide from Eli Lilly that activates GIP, GLP-1 and glucagon receptors. In a phase 3 obesity trial it produced about 28% average weight loss at 80 weeks, but it is not yet approved anywhere.

Structure

39 residues
  1. aK17C20 fatty diacid via γGlu-OEG linker (albumin binding)

Point at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.

Sequence as text
H-Y-Aib-Q-G-T-F-T-S-D-Y-S-I-αMeL-L-D-K-K-A-Q-Aib-A-F-I-E-Y-L-L-E-G-G-P-S-S-G-A-P-P-P-S-NH2

What it is used for

  • Obesity and overweight (studied)
  • Type 2 diabetes (studied)
  • Obstructive sleep apnea and knee osteoarthritis pain with obesity (studied)
  • Metabolic dysfunction-associated steatotic liver disease (studied)
  • Chronic kidney disease (studied)

How it works

Retatrutide combines three hormone actions in one peptide. GLP-1 and GIP receptor activation reduce calorie intake and improve glucose-dependent insulin release, while glucagon receptor activation raised energy expenditure in obese mice and is thought to add to weight and liver-fat loss. Aib and α-methyl-leucine residues protect it from enzymatic breakdown, and a C20 fatty diacid binds albumin, giving a half-life of about six days.

How strong the evidence is

ModerateAt least one good randomised trial, or consistent smaller human trials.

In a 48-week phase 2 trial (338 adults with obesity), 12 mg produced 24.2% mean weight loss versus 2.1% with placebo, and a liver substudy found liver fat normalized in 86% at 24 weeks. Lilly reported that in phase 3 TRIUMPH-1 participants on 12 mg lost 28.3% of body weight at 80 weeks versus 2.2% on placebo. TRANSCEND-T2D-1 (537 adults with type 2 diabetes, Lancet 2026) lowered HbA1c by 1.7 to 1.9 points versus 0.8 with placebo.

Risks and side effects

  • Nausea, diarrhea, vomiting and constipation, increasing with dose (nausea 42% at 12 mg vs 15% placebo in TRIUMPH-1)
  • Discontinuation for adverse events of 11.3% at 12 mg versus 4.9% with placebo in TRIUMPH-1
  • Dose-dependent heart rate increases, peaking around 24 weeks in phase 2
  • Long-term and cardiovascular outcome data not yet available
  • Not approved: products sold outside clinical trials are unregulated, with unknown identity, purity, dose and sterility

Regulatory status

No regulator has approved this peptide for any use.

Status by country

JurisdictionStatusSource
USUnited StatesNo authorised medicineSource 12
EUEuropean UnionNo authorised medicineSource 13
UKUnited KingdomNo authorised medicineSource 14
AUAustraliaNo authorised medicineSource 15
CACanadaNo authorised medicineSource 16
Whether a medicine containing it is authorised, checked in each regulator’s records on Oct 1, 2026.

Status of every peptide by country

Trials of Retatrutide to watch

  1. Phase 3Active, not recruiting

    TRANSCEND-T2D-2(opens the source in a new tab)

    Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2)

    Primary completion Aug 27, 20261,250 participantsSponsor: Eli Lilly and CompanyNCT06260722

  2. Phase 3Active, not recruiting

    TRIUMPH-5(opens the source in a new tab)

    A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity

    Primary completion expected November 2026800 participantsSponsor: Eli Lilly and CompanyNCT06662383

  3. Phase 3Active, not recruiting

    TRIUMPH-7(opens the source in a new tab)

    A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight and Chronic Low Back Pain

    Primary completion expected September 2027586 participantsSponsor: Eli Lilly and CompanyNCT07035093

  4. Phase 3Completed

    TRIUMPH-2(opens the source in a new tab)

    A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight

    Primary completion Jun 16, 20261,152 participantsSponsor: Eli Lilly and CompanyNCT05929079

  5. Phase 3Completed

    TRIUMPH-3(opens the source in a new tab)

    A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease

    Primary completion Apr 16, 20261,946 participantsSponsor: Eli Lilly and CompanyNCT05882045

  6. Phase 3Completed

    TRIUMPH-1(opens the source in a new tab)

    A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight

    Primary completion Apr 6, 20262,335 participantsSponsor: Eli Lilly and CompanyNCT05929066

  7. Phase 3Completed

    TRANSCEND-T2D-1(opens the source in a new tab)

    Effect of Retatrutide Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (TRANSCEND-T2D-1)

    Primary completion Jan 22, 2026537 participantsSponsor: Eli Lilly and CompanyNCT06354660

  8. Phase 3Completed

    TRIUMPH-4(opens the source in a new tab)

    A Study of Retatrutide (LY3437943) Once Weekly in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee

    Primary completion Nov 14, 2025445 participantsSponsor: Eli Lilly and CompanyNCT05931367

All trials to watch

Timeline

  1. 2027

    1. TRIUMPH-7

  2. 2026

    1. TRIUMPH-5
    2. Trial resultTRIUMPH-1 paper reports 25.0% weight loss with retatrutide at 80 weeks
    3. SafetyTGA finds undeclared semaglutide in counterfeit retatrutide after hospitalization
    4. TRANSCEND-T2D-2
    5. RegulatoryFDA warning letters reject 'research use only' labels on online GLP-1 peptide sales
    6. RegulatoryAustralian regulator seizes illegal peptides allegedly sold by a social media influencer
    7. Trial resultRetatrutide succeeds in TRIUMPH-2 and TRIUMPH-3; Lilly plans FDA filing in 2027
    8. TRIUMPH-2
    9. Trial resultRetatrutide lowers HbA1c by up to 1.94% in its first type 2 diabetes phase 3 trial
    10. Trial resultRetatrutide TRIUMPH-1: 28.3% average weight loss at 80 weeks on highest dose
    11. TRIUMPH-3
Show 7 earlier events

  1. 2026

    1. SafetyAustralia's TGA warns of severe reactions to unapproved injectable peptides
    2. SafetyHealth Canada warns against injecting peptides bought online and names seized products
    3. TRIUMPH-1
    4. TRANSCEND-T2D-1

  2. 2025

    1. Trial resultRetatrutide's first phase 3 trial: 28.7% weight loss and less knee pain
    2. TRIUMPH-4
    3. RegulatoryUK regulator raids first illegal weight-loss pen factory, seizing retatrutide pens

Articles about Retatrutide

Sources

  1. 01International Nonproprietary Names for Pharmaceutical Substances: Proposed INN List 128(opens the source in a new tab) World Health Organization (WHO Drug Information), 2022
  2. 02Retatrutide (D12430): sequence and structure entry(opens the source in a new tab) KEGG DRUG
  3. 03Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial(opens the source in a new tab) New England Journal of Medicine, 2023
  4. 04Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease(opens the source in a new tab) Nature Medicine, 2024
  5. 05LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b trial(opens the source in a new tab) The Lancet, 2022
  6. 06LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept(opens the source in a new tab) Cell Metabolism, 2022
  7. 07Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1)(opens the source in a new tab) The Lancet, 2026
  8. 08Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide(opens the source in a new tab) Nephrology Dialysis Transplantation, 2026
  9. 09Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1)(opens the source in a new tab) Eli Lilly and Company via PR Newswire, 2026
  10. 10Lilly reports second-quarter 2026 financial results (Form 8-K)(opens the source in a new tab) U.S. Securities and Exchange Commission (EDGAR), 2026
  11. 11World Anti-Doping Code International Standard: Prohibited List 2026(opens the source in a new tab) World Anti-Doping Agency, 2025
  12. 12FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss(opens the source in a new tab) U.S. Food and Drug Administration, 2026
  13. 13Find medicine: centrally authorised medicines(opens the source in a new tab) European Medicines Agency, 2026
  14. 14No summer shortcut for safe weight loss(opens the source in a new tab) Medicines and Healthcare products Regulatory Agency (GOV.UK), 2026
  15. 15Understanding your responsibilities when importing, compounding and supplying unapproved peptide products(opens the source in a new tab) Therapeutic Goods Administration, 2026
  16. 16Think twice before injecting peptides bought online: unauthorized products can seriously harm you(opens the source in a new tab) Health Canada, 2026
  1. In clinical trialsAmycretinUnimolecular GLP-1 and amylin receptor agonistNo single sequence68 WADA banned
  2. Not approvedAOD-9604Modified growth hormone fragment (research peptide)16 WADA banned
  3. In clinical trialsCagrilintideLong-acting amylin analog (amylin and calcitonin receptor agonist)37 WADA banned
  4. ApprovedDulaglutideGLP-1 receptor agonist (Fc fusion protein)31
  5. ApprovedExenatideGLP-1 receptor agonist39

Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.