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A guide to the active Phase 1, 2, and 3 retatrutide trials — including the populations, endpoints, and timeline for the next generation of human data.
The August 2023 New England Journal of Medicine publication of retatrutide's Phase 2 data was not the end of human evaluation — it was the trigger for a broad Phase 3 program. As of this writing, approximately 20 retatrutide trials are registered on ClinicalTrials.gov across all phases.
This article surveys what those trials are investigating, what data they will produce, and when the next major readouts can be expected.
Several Phase 1 and Phase 2 trials have already completed and either provided the foundational data or supplemented it:
NCT03841630 — The original first-in-human safety study. Phase 1, completed. Single-dose administration in healthy participants established the initial safety, tolerability, and pharmacokinetic profile.
NCT04143802 — Phase 1 study in participants with type 2 diabetes mellitus. Completed. Multi-dose safety and pharmacokinetics in the target population.
NCT04867785 — Phase 2 in participants with type 2 diabetes. Completed. Established efficacy in glucose handling and weight reduction in T2D specifically.
NCT04881760 — The Phase 2 obesity trial whose 48-week data was published in the 2023 NEJM paper. Completed.
NCT04823208 — Phase 1 in Japanese participants with T2D. Completed. Population-specific pharmacokinetic and pharmacodynamic data.
NCT05548231 — Phase 1 in Chinese participants. Completed.
NCT05611957 — Phase 1 in participants with impaired renal function. Completed. Important for understanding dose adjustments in patients with kidney disease, who are common in the target population.
NCT05916560 — Phase 1 in participants with hepatic impairment. Completed.
These early trials collectively establish the pharmacokinetic profile across populations and provide the safety baseline against which Phase 3 data will be evaluated.
The bulk of the upcoming data will come from Phase 3 trials targeting specific clinical indications. The Phase 3 program is divided across two main trial series:
The TRIUMPH series targets obesity and obesity with comorbidities.
NCT05882045 — Phase 3 in participants with obesity and established cardiovascular disease. Active, not recruiting. This trial includes cardiovascular outcomes endpoints — a critical safety and efficacy demonstration for any obesity drug. Expected readout in the next 1-2 years.
NCT07357415 — Phase 3 in participants without type 2 diabetes who have obesity or overweight. Recruiting. The primary obesity efficacy trial in the population most analogous to SURMOUNT-1 (tirzepatide) and STEP-1 (semaglutide), enabling direct cross-trial comparisons.
NCT07035093 — Phase 3 in obesity or overweight with chronic low back pain. Recruiting. Tests whether weight reduction translates to musculoskeletal symptom improvement — an outcome of clinical interest beyond weight itself.
The TRANSCEND series targets T2D populations.
TRANSCEND-T2D-1 (NCT06354660) — Phase 3 in adults with T2D and inadequate glycemic control on diet/exercise alone. Completed. Results not yet published as of this writing but expected imminently.
NCT05929079 — Phase 3 in participants with T2D who have obesity or overweight. Active, not recruiting. Combines the glucose-control and weight-loss endpoints relevant to the most clinically common T2D presentation.
Several trials are designed to answer specific mechanistic or safety questions rather than to establish indication-level efficacy:
NCT06039826 — Phase 1 in postmenopausal women with obesity or overweight. Completed. Addresses whether menopausal status affects pharmacological response.
NCT06313528 — Phase 1 examining calorie consumption and energy expenditure in participants with obesity. Completed. Mechanistic insight into whether retatrutide's effects on weight are mediated primarily by reduced intake, increased expenditure, or both.
NCT06808802 — Phase 1 examining whether retatrutide affects the pharmacokinetics of metoprolol (a beta-blocker). Completed. Drug-drug interaction characterization required for clinical use in patients on cardiovascular medications.
NCT06982846 — Phase 1 investigating retatrutide's effect on the hypoglycemic response in T2D. Active, not recruiting. Addresses whether triple agonism affects counter-regulatory hormone response to low blood sugar — important for combination use with insulin or sulfonylureas.
NCT07467447 — Phase 2 versus placebo in obesity or overweight. Recruiting. Additional confirmatory efficacy data.
The Phase 3 readouts, when they appear, will address several questions that the Phase 2 data could not:
Durability beyond 48 weeks. The Phase 2 trial duration was insufficient to establish whether weight loss plateaus and at what level. Phase 3 trials with 72-104 week durations will produce this data.
Effect size at scale. Phase 2 trials with hundreds of participants can produce effect estimates with relatively wide confidence intervals. Phase 3 trials with thousands of participants narrow those estimates substantially and detect rare safety signals.
Performance in specific populations. Effect size in elderly populations, patients with multiple comorbidities, patients with established cardiovascular disease, and patients with various metabolic complications may differ from the relatively healthy Phase 2 population.
Cardiovascular outcomes. The cardiovascular disease trial (NCT05882045) will produce the first definitive data on whether retatrutide reduces major adverse cardiovascular events — the outcome that ultimately drives clinical adoption in the metabolic disease space.
Comparison with tirzepatide. While no head-to-head trial is currently registered, similar trial designs across the TRIUMPH and SURMOUNT programs will enable cross-trial comparisons with stronger inference than the current Phase 2-only data permits.
For drug development of this scale and complexity:
Several of the Phase 3 trials initiated in 2022-2023 will read out beginning 2025-2026, with regulatory submissions likely in 2026-2027 and potential approval in late 2027 or 2028. These timelines are subject to change based on actual trial progression, regulatory queries, and manufacturing scale-up considerations.
The retatrutide development program represents one of the most ambitious obesity drug development efforts ever undertaken, with the trial portfolio designed to support:
The compound's eventual clinical role will be determined by how well the Phase 3 data confirms the Phase 2 efficacy signals and how the safety profile holds up at scale and over longer durations. The Phase 2 data was promising enough to justify this development scope; whether retatrutide ultimately becomes the dominant clinical option or settles into a more specialized role depends on what the next 24-36 months of trial readouts demonstrate.
NoteThis article is intended for informational and educational purposes only. It does not constitute medical advice.
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