What Is Retatrutide and Why Is It Being Studied?

Retatrutide is an investigational peptide compound developed by Eli Lilly. It acts as a triple incretin receptor agonist, meaning it targets three receptors simultaneously: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. That triple-receptor mechanism distinguishes it from approved GLP-1 single agonists and from dual GIP/GLP-1 agonists like tirzepatide, which is marketed as Mounjaro and Zepbound. Retatrutide itself is not approved under any brand name.

The scientific rationale for adding glucagon receptor activity is that glucagon stimulates energy expenditure in addition to the appetite and insulin-signaling effects driven by GIP and GLP-1 pathways. Preclinical work in rodent models suggested the combination could produce greater fat loss than dual agonism alone. Those animal-study findings informed the dose selection and design of the human trials that followed, though animal results do not predict human outcomes.

Researchers are studying retatrutide primarily in the context of obesity and type 2 diabetes. The compound is administered by subcutaneous injection once weekly in all trials published to date. This page tracks where those trials currently stand, not how the compound is used or obtained.

Phase 1 Results: What the Early Human Data Showed

Eli Lilly completed a Phase 1 first-in-human study to assess safety, tolerability, and pharmacokinetics. That trial enrolled healthy volunteers and participants with type 2 diabetes across single-ascending-dose and multiple-ascending-dose cohorts. The Phase 1 work established that retatrutide had a half-life consistent with once-weekly dosing and identified gastrointestinal side effects, primarily nausea and vomiting, as the most common adverse events, a pattern seen across the GLP-1 class.

Phase 1 data were not published as a standalone primary paper but were summarized in the Phase 2 trial report. The Phase 1 findings were sufficient for regulators to allow advancement into larger, longer trials. Phase 1 studies are designed to assess safety signals in small groups, typically fewer than 100 participants, and are not powered to measure efficacy outcomes.

Phase 2 Trial: Key Numbers and What They Mean

The pivotal Phase 2 trial (NCT04881760) enrolled 338 adults with a body mass index of 27 or higher and without type 2 diabetes. Participants were randomized across multiple dose cohorts and a placebo group. The trial ran 48 weeks. Results were published in the New England Journal of Medicine in June 2023 by Jastreboff and colleagues.

The highest-dose cohort in that trial showed a mean body weight reduction of 24.2% from baseline at 48 weeks, compared with 2.1% in the placebo group. Lower dose cohorts showed reductions ranging from approximately 8.7% to 17.5%. These are Phase 2 figures from a single randomized controlled trial; Phase 3 trials with larger sample sizes are required before any regulatory submission can occur.

A separate Phase 2 trial (NCT04867785) studied retatrutide in 281 adults with type 2 diabetes over 36 weeks. That trial, also published in the New England Journal of Medicine in 2023, reported HbA1c reductions and body weight changes across dose groups. Both trials were industry-sponsored and carried standard limitations including relatively short duration and selected patient populations.

Current Phase 3 Program: Trial Identifiers and Enrollment Status

Eli Lilly launched the TRIUMPH Phase 3 program for retatrutide. The program includes multiple trials targeting obesity, type 2 diabetes, and related cardiometabolic conditions. As of mid-2025, several TRIUMPH trials are listed as active or recruiting on ClinicalTrials.gov. Key identifiers include NCT05929066 (TRIUMPH-1, obesity without diabetes), NCT05929079 (TRIUMPH-2, obesity with type 2 diabetes), and NCT05959785 (TRIUMPH-3, cardiovascular outcomes).

TRIUMPH-1 and TRIUMPH-2 are designed as 72-week randomized, double-blind, placebo-controlled trials with sample sizes in the thousands, substantially larger than the Phase 2 work. The cardiovascular outcomes trial is longer by design, as regulators typically require cardiovascular safety data for weight-management drugs before or shortly after approval. Enrollment figures and completion dates are updated on ClinicalTrials.gov as sites report.

A Phase 3 trial in non-alcoholic steatohepatitis (NASH), listed as NCT06015490, is also part of the broader retatrutide development program. NASH trials require liver biopsy endpoints and tend to run longer than obesity trials. This trial is in an earlier enrollment stage relative to the TRIUMPH obesity studies.

Phase 3 completion across the core TRIUMPH trials is anticipated in 2026 based on estimated primary completion dates listed on ClinicalTrials.gov. Those dates are estimates and subject to change based on enrollment pace, protocol amendments, and regulatory requests.

Regulatory Pathway: What Comes After Phase 3?

If Phase 3 data meet the pre-specified endpoints, Eli Lilly would submit a New Drug Application (NDA) to the FDA. The FDA review process for a standard application typically takes 10 to 12 months from submission, though priority review designation can shorten that to 6 months. No NDA for retatrutide has been submitted as of mid-2025.

For context on how the approval process works with this drug class: semaglutide's branded forms Wegovy and Ozempic are FDA-approved prescription drugs. Tirzepatide's branded forms Mounjaro and Zepbound are FDA-approved prescription drugs. Research-chemical versions of those compounds sold outside the pharmaceutical supply chain are not approved drugs regardless of their chemical similarity. The same framework would apply to retatrutide if it eventually receives approval under a brand name.

The FDA has not granted retatrutide Breakthrough Therapy designation as of the time of this writing, though Eli Lilly has not publicly ruled out seeking it. Breakthrough designation, if granted, would add FDA collaboration during development but would not guarantee approval or accelerate the Phase 3 work already underway.

Evidence Tier Summary

It's useful to be clear about what level of evidence currently exists for retatrutide. There are two published Phase 2 randomized controlled trials in humans, both in the New England Journal of Medicine, covering obesity and type 2 diabetes populations. Those are the strongest data available right now. Phase 3 trials are ongoing and have not reported primary results.

Preclinical data from rodent and non-human primate studies informed the compound's development but are not predictive of human outcomes. No long-term safety data beyond 48 to 72 weeks exist in humans. The Phase 3 cardiovascular outcomes trial is specifically designed to fill part of that gap, but results are years away.

Retatrutide has not been studied in pediatric populations, pregnant individuals, or people with severe renal or hepatic impairment in any published trial. Those populations are typically excluded from early-phase trials and studied separately if a compound advances to approval.