PEPTIDEREPORT

Investigational once-weekly peptide agonist of GIP, GLP-1, and glucagon receptors

Retatrutide

Retatrutide has produced large weight reductions in randomized Phase 2 and Phase 3 trials, but it remains unapproved. Long-term outcomes, direct comparisons, rare risks, durability, and final regulatory decisions remain unresolved.

Regulatory watch Last reviewed Jul 12, 2026 Next review Aug 12, 2026
Fictional RETA autoinjector concept photographed with realistic molded seams and three printed color bands

Evidence snapshot

Regulatory: no approval; FDA says it cannot be compounded and has not been found safe and effective for any condition.

Phase 2 obesity: 338 adults, 48 weeks, up to 24.2% mean loss at week 48.

Phase 3 obesity: TRIUMPH-1 reported up to 28.3% at week 80; full obesity publication was not yet peer-reviewed at the cutoff.

Phase 3 diabetes: TRANSCEND-T2D-1 was peer-reviewed in The Lancet and showed HbA1c and weight reductions at week 40.

Outcomes: cardiovascular and kidney outcomes remain under study.

Research record

What the evidence record says

Retatrutide is an investigational peptide that activates GIP, GLP-1, and glucagon receptors. In the 338-person Phase 2 obesity trial, the highest-dose group lost a mean 17.5% at 24 weeks and 24.2% at 48 weeks. Lilly later reported up to 28.3% mean loss at 80 weeks in the pivotal TRIUMPH-1 Phase 3 obesity trial. Retatrutide remains unapproved, and FDA says it cannot be used in compounding under federal law.

Evidence grade
Human Phase 3 evidence
Regulatory status
Investigational and not approved by FDA, EMA, or any regulatory agency as of July 12, 2026. FDA states that retatrutide cannot be used in compounding under federal law.
Also known as
LY3437943

Evidence records

Studies, registries, reviews, and regulatory records

Phase 2 obesity, NEJM 2023

  • 338 adults with obesity, or overweight plus a weight-related condition, without diabetes.
  • Randomized, double-blind, placebo-controlled; all groups received lifestyle counseling.
  • Primary endpoint was percent weight change at week 24.
  • Week 24: −7.2%, −12.9%, −17.3%, and −17.5% across 1, 4, 8, and 12 mg versus −1.6% placebo.
  • Week 48: −8.7%, −17.1%, −22.8%, and −24.2% versus −2.1% placebo.
  • GI adverse effects were dose-related; heart rate rose dose-dependently to week 24 and declined at weeks 36 and 48.
  • Limitations: Phase 2 size, 48 weeks, United States only, majority White, only 4% in the overweight category, no cardiovascular or mortality outcomes, sponsor funded.

Records: Retatrutide phase 2 results: 24.2% weight loss (NEJM)

TRIUMPH-1 Phase 3 obesity

  • NCT05929066; 2,339 participants; randomized, double-blind, placebo-controlled.
  • Sponsor-reported efficacy-estimand results at week 80: 4 mg −19.0%, 9 mg −25.9%, 12 mg −28.3%, placebo −2.2%.
  • Selected extension: among baseline-BMI-at-least-35 participants who completed the main study and tolerated assigned medication, the 12 mg assignment reached −30.3% at week 104.
  • Safety: nausea 28.6%, 38.4%, 42.4% versus 14.8% placebo; vomiting 10.6%, 22.8%, 25.3% versus 4.8%; dysesthesia 5.1%, 12.3%, 12.5% versus 0.9%; adverse-event discontinuation 4.1%, 6.9%, 11.3% versus 4.9%.
  • Evidence label: Phase 3 randomized results presented at ADA and reported by sponsor; no full peer-reviewed obesity paper at cutoff.

Records: Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial., The First Phase 3 Obesity Study of Retatrutide in People with Obesity (TRIUMPH-1).

TRANSCEND-T2D-1 Phase 3

  • NCT06354660; 537 adults with type 2 diabetes inadequately controlled by diet and exercise alone; 40 weeks; 48 sites in the US, Mexico, and India.
  • Treatment-regimen HbA1c change: −1.69%, −1.86%, −1.94% versus −0.81% placebo.
  • Treatment-regimen weight change: −11.5%, −13.9%, −15.3% versus −2.6% placebo.
  • 91% completed treatment on study drug; discontinuation for adverse events was 2–5% versus 0%; no severe hypoglycemia.
  • Two deaths occurred in the 4 mg group and were judged unrelated.
  • Limitations: 40 weeks, relatively early and medication-naive diabetes, no cardiovascular-outcome conclusion; Lilly funded, with six employee/shareholder authors.

Records: Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.

TRIUMPH-4

  • NCT05931367; 445 adults with obesity or overweight and knee osteoarthritis.
  • At 68 weeks Lilly reported −26.4% and −28.7% weight change for 9 and 12 mg versus −2.1% placebo.
  • WOMAC pain improved, but percentage pain changes highlighted by Lilly were post hoc.
  • Evidence label: sponsor-reported Phase 3 result without a full peer-reviewed paper at cutoff.

Records: 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.

Evidence timeline

What changed, and when

  1. Phase 2 obesity results were published, with week 24 as the primary endpoint and week 48 as a secondary endpoint.

    Records: Retatrutide phase 2 results: 24.2% weight loss (NEJM)

  3. EMA agreed to a pediatric investigation plan for obesity; this was not marketing authorization.

    Records: EMEA-003258-PIP02-23: retatrutide paediatric investigation plan.

  4. Lilly announced positive TRIUMPH-4 Phase 3 topline results in obesity with knee osteoarthritis.

    Records: 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.

  6. Lilly announced positive TRIUMPH-1 pivotal obesity results.

    Records: Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial.

Direct answers

Frequently asked questions

What receptors does retatrutide target?

It activates GIP, GLP-1, and glucagon receptors in a single investigational molecule.

Records: Retatrutide phase 2 results: 24.2% weight loss (NEJM)

Is retatrutide approved?

No. It remained unapproved by any regulatory agency as of July 12, 2026.

Records: FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss., What to know about retatrutide.

Can it legally be compounded?

FDA says retatrutide cannot be used in compounding under federal law.

Records: FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss.

What was the exact Phase 2 result?

At 12 mg, mean weight change was −17.5% at week 24 and −24.2% at week 48.

Records: Retatrutide phase 2 results: 24.2% weight loss (NEJM)

What did TRIUMPH-1 report?

Lilly reported −19.0%, −25.9%, and −28.3% at week 80 for 4, 9, and 12 mg in the efficacy estimand.

Records: Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial.

Is the 30.3% figure representative of everyone?

No. It came from a selected extension of baseline-BMI-at-least-35 participants who completed the main trial and tolerated treatment.

Records: Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial.

What adverse effects have appeared?

Gastrointestinal events were most common; dose-related dysesthesia and treatment discontinuation were also reported in Phase 3 obesity results.

Records: Retatrutide phase 2 results: 24.2% weight loss (NEJM), Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial., Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.

Has it been compared directly with tirzepatide?

A direct-comparison trial is registered, but no completed result was identified at the cutoff.

Records: TRIUMPH-5: retatrutide compared with tirzepatide in adults with obesity.

Does an EMA pediatric plan mean European approval?

No. A pediatric investigation plan is a development requirement, not marketing authorization.

Records: EMEA-003258-PIP02-23: retatrutide paediatric investigation plan.

Open research questions

What is still unknown

  • FDA and EMA review outcomes and final indications, if any.
  • Full peer-reviewed TRIUMPH-1 and TRIUMPH-4 publications.
  • Long-term cardiovascular, renal, mortality, gallbladder, pancreatic, psychiatric, nutritional, and reproductive outcomes.
  • Rare adverse events after much larger exposure.
  • Weight regain and metabolic outcomes after discontinuation.
  • Lean-mass and bone effects during very large weight loss.
  • Direct efficacy and tolerability versus tirzepatide.
  • Durability beyond two years and performance in older or medically complex populations.

Tracked claims

It burns fat because of glucagon agonism.

Evidence level: Mechanistic Simplification

Sources: Retatrutide phase 2 results: 24.2% weight loss (NEJM)

How to read this: Triple-receptor activity is established, but individual clinical effects cannot be assigned to one receptor from these trials.

No plateau means weight loss will continue indefinitely.

Evidence level: Unsupported by the cited record

Sources: Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial., Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.

How to read this: An observed trajectory inside a fixed trial does not establish indefinite continued loss.

Linked public records

Regulatory actions involving Retatrutide

View the full Regulatory Watch

Free report

Get the source-quality checklist

Use the same checklist Peptide Report uses to separate Retatrutide claims, source records, supplier documentation, and media signals.

V1 collects email, role, and topic interest only. No medication, health-condition, dosing, or current-use data is collected in this form.

Formspree processes this submission for Peptide Report. Privacy notice.

Sources on this page

Each source record is linked to the claim or evidence note it supports.

Retatrutide for Obesity: A Phase 2 Trial

New England Journal of Medicine · Peer reviewed · Jun 26, 2023 · accessed Jul 1, 2026

Retatrutide phase 2 obesity trial (NEJM 2023): at 12 mg, mean body weight fell 17.5% at week 24 and 24.2% at week 48; GI adverse events were most common.

12 linked pagesOpen original · nejm-retatrutide-phase2-2023

What to know about retatrutide.

Eli Lilly and Company · Official company source · 2026 · accessed Jul 12, 2026

Eli Lilly and Company. What to know about retatrutide. Current 2026 status page.

1 linked pageOpen original · research-reta-03

Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.

National Library of Medicine · Peer reviewed · 2026 · accessed Jul 12, 2026

Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide 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. doi:10.1016/S0140-6736(26)00967-0. PMID 42250575.

1 linked pageOpen original · research-reta-06

Related compounds

Semaglutide

Semaglutide is a GLP-1 receptor agonist sold as Ozempic, Wegovy, and Rybelsus for specific FDA-approved indications. Ran...

Evidence review

Tirzepatide

Tirzepatide is a dual GIP and GLP-1 receptor agonist sold as Mounjaro and Zepbound for specific FDA-approved indications...

Evidence review

Stay informed

Track Retatrutide with Peptide Report

Get FDA Watch Alerts for Retatrutide Subscribe for regulatory updates, new trial data, and source-backed claim revisions.
See claims about Retatrutide fact-checked 7 video claims checked in our video claim scanner.
Compare Retatrutide with similar compounds 1 comparison page available: Retatrutide vs Tirzepatide

Using Retatrutide in a stack?

Check interaction warnings, half-life conflicts, and reconstitution issues before combining compounds.

Check your stack