Retatrutide (LY3437943): status, trials and research tools

What retatrutide is

Retatrutide, development code LY3437943, is an investigational drug from Eli Lilly. It is a single peptide that activates three hormone receptors: the GIP receptor, the GLP-1 receptor and the glucagon receptor. (Cell Metabolism, Aug 18, 2022) Lilly calls it a “triple agonist”. Online, it is often nicknamed “GLP-3”, which is not an official name.

In laboratory testing, retatrutide showed balanced activity at the glucagon and GLP-1 receptors and more activity at the GIP receptor. (Cell Metabolism, Aug 18, 2022) In the same paper’s mouse studies, the authors linked the glucagon component to higher energy expenditure and the GIP and GLP-1 components to lower food intake. Those are animal findings; human trials measure outcomes such as weight and HbA1c rather than each receptor’s contribution.

Its half-life in a Phase 1b trial in type 2 diabetes was approximately 6 days, and its pharmacokinetics were dose proportional. (The Lancet, Oct 27, 2022) Lilly’s Phase 2 protocol summarized the first-in-human single-dose study as showing peak levels about 1 to 3 days after a dose and a mean terminal half-life of about 5 to 7 days. (Eli Lilly, hosted on ClinicalTrials.gov, Aug 29, 2022) That is why every trial gave retatrutide once weekly as a subcutaneous dose. The retatrutide plotter uses the 6-day half-life to model the relative amount of drug over a published trial schedule; it is a research visualization, not dosing guidance.

As of October 19, 2026, retatrutide is not approved by the FDA or any other regulator. (Eli Lilly, Aug 12, 2026) The full status, with a dated timeline, is in is retatrutide FDA approved.

How it differs from tirzepatide and semaglutide

The three drugs share a family resemblance: all act on the GLP-1 receptor, and all are given once weekly in their subcutaneous forms. The difference is how many receptors each one targets and where each stands with FDA.

(The Lancet, Oct 27, 2022) (Eli Lilly, May 13, 2022) (DailyMed, Aug 27, 2026) (FDA, Nov 8, 2023) (Novo Nordisk, Jun 18, 2026) (FDA, Oct 19, 2026) (FDA, Oct 19, 2026)

The glucagon-receptor activity is what makes retatrutide different. Glucagon receptor agonism is not part of how tirzepatide or semaglutide work. Retatrutide’s safety profile also has a feature not typical of GLP-1 drugs: dysesthesia, an abnormal skin sensation, which reached 12.5% on 12 mg versus 0.9% on placebo in TRIUMPH-1. (Eli Lilly, May 21, 2026)

No published trial has compared retatrutide directly with tirzepatide yet. TRIUMPH-5 is that trial, and ClinicalTrials.gov lists it as active, not recruiting, with primary completion estimated for November 2026. (ClinicalTrials.gov, Jul 20, 2026) Until it reports, any comparison relies on separate trials with different populations, durations and analyses. See retatrutide vs tirzepatide for a caveated side-by-side.

Development timeline

• August 2022: Cell Metabolism paper introduces LY3437943 and reports the first single-dose human study. (Cell Metabolism, Aug 18, 2022)
• June 2023: Phase 2 obesity results in NEJM: −24.2% on 12 mg versus −2.1% on placebo at 48 weeks. (N Engl J Med, Jun 26, 2023)
• December 11, 2025: First Phase 3 topline, TRIUMPH-4 in knee osteoarthritis. (Eli Lilly, Dec 11, 2025)
• March 19, 2026: TRANSCEND-T2D-1 topline in type 2 diabetes. (Eli Lilly, Mar 19, 2026)
• May 21, 2026: TRIUMPH-1 topline in obesity. (Eli Lilly, May 21, 2026)
• July 23, 2026: TRIUMPH-2 and TRIUMPH-3 topline. (Eli Lilly, Jul 23, 2026)
• September 29, 2026: TRIUMPH-1 published in NEJM; Lilly restates its Q1 2027 BLA plan. (N Engl J Med, Sep 29, 2026) (Eli Lilly, Sep 29, 2026)

What the trials measured

The Phase 3 program, called TRIUMPH, used five dose strengths: 2, 4, 6, 9 and 12 mg. Participants assigned to retatrutide started at 2 mg once weekly and stepped up every four weeks until they reached their target dose of 4, 9 or 12 mg. (Eli Lilly, Dec 11, 2025) The titration tool lays out those published schedules.

The main endpoint in the obesity trials was percent change in body weight; the diabetes trials also measured HbA1c, and other trials measured knee pain, sleep apnea severity and cardiovascular events. Each result is reported two ways. Lilly’s releases lead with the efficacy estimand (as if everyone stayed on treatment), and the journals lead with the treatment-regimen estimand (everyone randomized). In TRIUMPH-1, 12 mg produced −28.3% on the first and −25.0% on the second, versus −2.2% and −3.9% on placebo. (Eli Lilly, May 21, 2026) (N Engl J Med, Sep 29, 2026) Every trial, both estimands and the caveats on the 104-week extension are in the retatrutide trial results guide, and adverse-event rates by dose are in the side effects guide.

Why research-use sellers are not the same as the trial drug

Retatrutide is widely advertised online as a “research peptide”. Those products are not the drug used in Lilly’s trials, and nothing about their contents, purity or dose has been reviewed by FDA.

FDA has said so in writing. Warning letters dated December 10, 2024, March 31, 2026 and August 24, 2026 treat retatrutide sold online as an unapproved new drug, including products labeled “research purposes only” and products sold under names such as “GLP-1-R peptide” and “GLP-3R”. (FDA, Dec 10, 2024) (FDA, Mar 31, 2026) (FDA, Aug 24, 2026) A September 9, 2025 letter says compounded retatrutide does not qualify for the exemptions that allow pharmacies to compound some drugs. (FDA, Sep 9, 2025)

Lilly states that retatrutide is an investigational molecule that cannot be legally sold or marketed for human use. (Eli Lilly, Sep 29, 2026) On August 12, 2026, it announced six new U.S. lawsuits against sellers and said it had reported more than 14,000 websites, advertisements, posts and listings in over 100 countries. (Eli Lilly, Aug 12, 2026)

The trial results on this site describe Lilly’s study drug, given under a protocol with medical monitoring. They do not describe any product bought outside a trial.