Retatrutide Clinical Trials

Summary: Retatrutide is in Phase 3 across the TRIUMPH program after a 2023 Phase 2 trial produced 24.2% weight loss at 48 weeks on the 12 mg dose. The drug is not yet FDA-approved as of mid-2026, with NDA filing widely expected in late 2026 or 2027.

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Retatrutide is the most-watched drug in obesity medicine that you cannot yet buy. Eli Lilly's triple agonist of the GIP, GLP-1, and glucagon receptors has produced the largest weight loss numbers ever recorded in a randomized trial, and the company is running a multi-arm Phase 3 program called TRIUMPH to convert that signal into an FDA-approvable label. As of May 2026, retatrutide is not approved by any regulator. It is investigational. Here is the trial-by-trial map of what has been published, what is enrolling, and when the data will read out.

What retatrutide is, in one paragraph

Retatrutide (development name LY3437943) is a single peptide that activates three hormone receptors at once: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon (GCG). Compared with the endogenous ligands, it is more potent at GIP and modestly less potent at GLP-1 and glucagon ^[1]. The pharmacokinetics support once-weekly subcutaneous dosing, with a terminal half-life of approximately six days. Adding glucagon receptor activity to the GIP and GLP-1 mechanism already proven by tirzepatide is the design bet: glucagon agonism is hypothesized to increase resting energy expenditure and amplify the weight-loss effect rather than just suppress appetite.

Phase 1: pharmacokinetics and first-in-human data

The Phase 1 program ran from 2019 through 2022 in single-ascending-dose and multiple-ascending-dose studies. The headline findings were dose-proportional pharmacokinetics, a half-life around six days that supports weekly injection, and a dose-dependent reduction in body weight in participants without diabetes. The same Phase 1 framework included a Phase 1b trial in adults with type 2 diabetes (T2D). In that trial, retatrutide at the 12 mg dose produced a placebo-adjusted least-squares mean weight reduction of 8.96 kg, roughly 10 percent of body weight, after 12 weeks of treatment ^[1]. That early signal is what convinced Lilly to push retatrutide into the larger Phase 2 obesity program.

Gastrointestinal side effects were the dominant adverse events even in Phase 1, and they were dose-related. The pattern matched what semaglutide and tirzepatide had already shown: slow dose escalation reduces but does not eliminate nausea and vomiting at therapeutic doses. Heart-rate increases were observed at higher doses, a class effect for GLP-1-based therapies, and they peaked during dose escalation and partially attenuated thereafter.

Phase 2 obesity trial: Jastreboff et al, NEJM 2023

This is the trial that put retatrutide on the cover of obesity medicine. Jastreboff and colleagues conducted a 48-week, double-blind, randomized, placebo-controlled trial at multiple US sites, registered as NCT04881760 and published in the New England Journal of Medicine in July 2023 ^[1].

Design. 338 adults with BMI 30 to 50, or BMI 27 to under 30 with at least one weight-related condition. Diabetes was an exclusion criterion. Participants were randomized 2:1:1:1:1:2:2 across seven arms: retatrutide 1 mg, 4 mg (with 2 mg or 4 mg initial dose), 8 mg (with 2 mg or 4 mg initial dose), 12 mg (with 2 mg initial dose), and placebo. All injections were subcutaneous, weekly, for 48 weeks. Lifestyle counseling was provided to every arm.

Primary endpoint. Percent change in body weight from baseline to 24 weeks. Secondary endpoints included percent change at 48 weeks and the proportion of participants achieving 5%, 10%, and 15% weight reductions.

Headline result. Least-squares mean weight change at 48 weeks was negative 24.2% in the 12 mg group versus negative 2.1% on placebo ^[1]. Lower doses produced 17.1% loss at 4 mg and 22.8% loss at 8 mg. The weight-loss curves had not plateaued by week 48, which means a longer trial would likely have shown more weight loss.

Why this matters. No prior anti-obesity drug had hit 24% mean weight loss in a randomized trial at 48 weeks. Tirzepatide's SURMOUNT-1 produced 22.5% at 72 weeks on the 15 mg dose. Retatrutide reached 24.2% in three fewer months, and the curves were still falling.

Safety. Adverse events were predominantly gastrointestinal, dose-related, and mostly mild to moderate. Nausea, vomiting, diarrhea, and constipation were the most common. A 2 mg starting dose mitigated GI events compared with a 4 mg start. Dose-dependent heart-rate increases peaked at 24 weeks and declined thereafter. The trial completion rate was 81%, with 71% completion in placebo and 76% to 87% across retatrutide arms.

Phase 2 type 2 diabetes trial: Rosenstock et al, Lancet 2023

Published in The Lancet in August 2023, the Rosenstock T2D Phase 2 trial answered the parallel question: does retatrutide also lower glucose, and how much weight does it remove in people who already have T2D ^[2].

Design. Randomized, double-blind, placebo and active-controlled, parallel-group trial in adults with T2D. Doses tested included retatrutide 0.5 mg, 4 mg (with 2 mg or 4 mg initial dose), 8 mg (with 2 mg or 4 mg initial dose), and 12 mg (with 2 mg initial dose), plus placebo and an active comparator arm with dulaglutide 1.5 mg. Treatment ran 36 weeks.

Headline result. HbA1c reductions reached up to 2.0% (about 20 mmol/mol) on retatrutide 12 mg, alongside body weight reductions of up to 16.9% ^[2]. The investigators described the combined glycemic and weight effects as the largest reported for a glucose-lowering agent at the time of publication. Dulaglutide 1.5 mg in the same study delivered the expected HbA1c reduction near 1.4% and modest weight loss, putting retatrutide's effect in clear context.

Why this matters. Retatrutide can pursue a dual indication (obesity and T2D), the same regulatory pathway Lilly took with tirzepatide as Mounjaro and Zepbound. The Phase 2 T2D data is what unlocked the TRANSCEND-T2D Phase 3 program in parallel with the TRIUMPH obesity trials.

Phase 3: the TRIUMPH program

TRIUMPH is the Phase 3 umbrella program for obesity and obesity-adjacent indications. TRANSCEND-T2D is the parallel diabetes program. Together they cover at least eight registrational and supplemental trials. As of May 2026, only TRIUMPH-4 has reported top-line results.

TRIUMPH-1: obesity, general population

NCT05929066. The pivotal weight-management trial for FDA approval. Approximately 2,500 adults with BMI 30 or higher, or BMI 27 or higher with a weight-related comorbidity, randomized to retatrutide or placebo for 72 weeks ^[3]. Primary endpoint: percent change in body weight. This is the trial that becomes the primary efficacy basis for Lilly's New Drug Application. Top-line results are expected in 2026.

TRIUMPH-2: obesity with type 2 diabetes

NCT05929079. Approximately 1,400 adults with obesity and T2D, treated for 52 weeks. Co-primary endpoints are percent body-weight change and HbA1c reduction ^[3]. A positive readout supports the dual indication strategy. Expected to report in 2026.

TRIUMPH-3: obesity with established cardiovascular disease

NCT05882045. Approximately 1,800 adults with BMI 30 or higher and established cardiovascular disease. The trial is 113 weeks long, designed to assess both weight-loss efficacy and cardiovascular safety in a high-risk population ^[3]. Status as of May 2026: active, not recruiting. A separate, larger cardiovascular outcomes trial (often labeled TRIUMPH-Outcomes, NCT06383390) is enrolling adults with obesity plus atherosclerotic cardiovascular disease or chronic kidney disease, with major adverse cardiac events (MACE) and major adverse kidney events as endpoints. That outcomes trial is the analog of semaglutide's SELECT trial and reports later, likely 2028 or 2029.

TRIUMPH-4: obesity with knee osteoarthritis

NCT05931367. The first Phase 3 result to read out. TRIUMPH-4 enrolled 445 adults with BMI 27 or higher and moderate knee osteoarthritis, treated for 68 weeks with retatrutide 4 mg, 9 mg, or 12 mg versus placebo. Top-line results announced in December 2025 showed mean weight loss of 28.7% on the 12 mg dose and 26.4% on the 9 mg dose, with significant improvements in WOMAC pain scores ^[4]. This is the highest mean weight loss reported in any randomized obesity trial to date and the data that anchors investor expectations for the rest of TRIUMPH.

Other Phase 3 trials in the program

The TRIUMPH umbrella also includes a weight-maintenance trial (NCT06859268, the 80-week lead-in plus 36-week randomized withdrawal design), trials in adolescents, and Phase 3b extensions like NCT07232719 for additional efficacy and safety questions ^[3]. The TRANSCEND-T2D Phase 3 program runs in parallel as three trials in adults with T2D, including TRANSCEND-T2D-3 (NCT06297603) in participants with renal impairment. Eli Lilly announced positive top-line TRANSCEND-T2D-1 results in early 2026 showing significant HbA1c and weight reductions versus placebo ^[4].

Retatrutide for obstructive sleep apnea

A nested or dedicated sleep apnea analysis is part of the TRIUMPH program, with approximately 600 adults having moderate-to-severe obstructive sleep apnea. The primary endpoint is change in apnea-hypopnea index (AHI) at 52 weeks. The logic mirrors tirzepatide's SURMOUNT-OSA trial, which led to the first FDA approval of a GLP-1-class drug for OSA. If retatrutide produces a comparable AHI reduction with its larger weight-loss effect, it becomes a candidate for an OSA label expansion after the initial obesity approval.

Retatrutide for MASH and liver outcomes

Metabolic dysfunction-associated steatohepatitis (MASH) is on the trial map. A dedicated Phase 2/3 program is in planning or early enrollment, separate from the main TRIUMPH-1 obesity trial. Results are not expected before 2027. Liver-fat reduction was already a striking secondary signal in the Phase 2 obesity data, and the glucagon receptor activity is mechanistically attractive for fatty liver disease.

Regulatory status and FDA timeline

Retatrutide has no marketing authorization anywhere in the world as of May 2026. The expected regulatory path:

• NDA submission to FDA. Most likely Q4 2026 or Q1 2027, contingent on TRIUMPH-1 and TRIUMPH-2 reading out positive. Eli Lilly has signaled the late-2026 timeframe in earnings calls.
• FDA review. Standard review is 10 months; Priority Review is 6 months. Lilly may request Priority Review given the magnitude of the TRIUMPH-4 weight-loss benefit. The FDA had not granted any expedited designation as of April 2026.
• Earliest possible approval. Late 2027 to mid-2028, depending on the review category and whether the FDA issues a complete response letter requiring additional data.
• Brand and indication. Lilly has not announced a brand name. The Phase 3 program is designed to support indications for chronic weight management, T2D, and potentially cardiovascular risk reduction in obesity. A separate label expansion for OSA is possible after initial approval.

Safety profile across the trials so far

Aggregating Phase 1, Phase 2 obesity, Phase 2 T2D, and TRIUMPH-4 top-line data:

• Gastrointestinal events dominate the safety profile: nausea, vomiting, diarrhea, constipation. Dose-related, mostly mild to moderate, partially mitigated by slow titration.
• Heart-rate increases at higher doses, peaking during titration and declining over time. Comparable in magnitude to tirzepatide and semaglutide.
• No new safety signals specific to glucagon receptor agonism have emerged in the published data so far. Liver enzymes, lipase, and amylase have been monitored without flagging dose-limiting findings, though Phase 3 will refine this.
• Class warnings for GLP-1-based therapies (pancreatitis, gallbladder events, medullary thyroid carcinoma in animal models) are still tracked in the TRIUMPH program. The eventual label will reflect Phase 3 incidence rates.

How retatrutide compares to semaglutide and tirzepatide on trial data

Cross-trial comparisons are imperfect because trial durations, populations, and titration schedules differ. With that caveat in mind:

The TRIUMPH-4 number is from a population with knee osteoarthritis on a refined dose-escalation, so it is not directly comparable to TRIUMPH-1 (the eventual primary efficacy trial), but it sets expectations. If TRIUMPH-1 lands between 24% and 28% mean weight loss at 72 weeks, retatrutide will have the largest efficacy of any anti-obesity medication in history.

What this article does not cover

Pricing, insurance coverage, compounding, and access strategies for retatrutide do not exist yet because there is no approved product. Any "retatrutide" available for purchase today is unapproved, unregulated, and not the same compound studied in TRIUMPH. The clinical-trial enrollment process, eligibility criteria for specific sites, and how to participate in a TRIUMPH trial are covered in their own articles. For the underlying mechanism and how retatrutide differs from a dual GIP/GLP-1 agonist like tirzepatide, see the dedicated mechanism article.

Common questions about retatrutide trials

When will retatrutide be FDA-approved?

Earliest plausible approval is late 2027 to mid-2028, contingent on positive TRIUMPH-1 and TRIUMPH-2 readouts in 2026 and a subsequent Lilly NDA filing. As of May 2026 retatrutide is not approved.

What were the Phase 2 retatrutide results?

The 48-week Phase 2 obesity trial (Jastreboff, NEJM 2023) produced 24.2% mean weight loss on the 12 mg dose versus 2.1% on placebo, with 83% of 12 mg participants losing at least 15% of body weight.

What did the Phase 2 diabetes trial show?

The Rosenstock Lancet 2023 trial showed HbA1c reductions up to 2.0% and weight loss up to 16.9% on retatrutide 12 mg in adults with T2D over 36 weeks, exceeding the dulaglutide active comparator.

Is retatrutide better than tirzepatide?

Cross-trial comparisons favor retatrutide on weight loss (24.2% Phase 2 at 48 weeks versus tirzepatide 22.5% at 72 weeks in SURMOUNT-1), but no head-to-head randomized trial has been published. Direct comparison would require a dedicated trial.

What is the TRIUMPH program?

TRIUMPH is Eli Lilly's Phase 3 umbrella program for retatrutide in obesity and related conditions. It includes TRIUMPH-1 (general obesity), TRIUMPH-2 (obesity with T2D), TRIUMPH-3 (obesity with CVD), TRIUMPH-4 (obesity with knee osteoarthritis), and TRIUMPH-Outcomes (cardiovascular and kidney outcomes).

What were the TRIUMPH-4 results?

Top-line results announced in December 2025 showed 28.7% mean weight loss on retatrutide 12 mg at 68 weeks versus 2.1% on placebo, plus significant WOMAC knee-pain improvement. Full publication is expected in 2026.

Is retatrutide being tested for sleep apnea?

Yes, a sleep apnea arm or nested study within the TRIUMPH program enrolls adults with obesity and moderate-to-severe obstructive sleep apnea, with apnea-hypopnea index as the primary endpoint. Results timing is later 2026 or 2027.

Can I enroll in a retatrutide clinical trial?

TRIUMPH-1, TRIUMPH-2, the weight-maintenance trial, and TRANSCEND-T2D trials are still recruiting at sites across the US, Canada, and globally. Search ClinicalTrials.gov by the relevant NCT number for site locations and eligibility.

What is the difference between TRIUMPH and TRANSCEND-T2D?

TRIUMPH covers obesity and obesity-related indications. TRANSCEND-T2D is the parallel Phase 3 program for adults with type 2 diabetes, run as three registrational trials including one in renal-impairment populations.

Is compounded retatrutide the same as the trial drug?

No. Retatrutide has no approved active pharmaceutical ingredient source. Compounded or peptide-vendor retatrutide is not the product studied in the TRIUMPH trials, and its purity, potency, and stability cannot be verified.