Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial
- Design
- Randomized trial · 338 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationObesity; weight-loss dose-finding trial. Included here for the heart-rate safety signal and as the reference for triple-agonist programmes.
- Could weight loss explain it?
- Not applicable[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 2[Auto] Randomized trial of moderate size; outcome type and follow-up limit certainty (auto-provisional).
- Assessment
- Version 2 · curated · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
Phase 2 trial of the triple agonist retatrutide: up to 24% weight loss at 48 weeks in adults with obesity, with dose-related gastrointestinal effects and increases in heart rate. Sets the stage for TRIUMPH and TRANSCEND trials.
01Findings
What the study reported
- Drugs
- Retatrutide
- Dose
- 1 to 12 mg weekly
- Route
- subcutaneous
- Treatment duration
- 48 weeks
- Comparator
- placebo
- Primary outcome
- Percent change in body weight at 24 weeks
- Effect
- -24.2% at 48 weeks (12 mg) vs -2.1% placebo; dose-dependent heart-rate increase peaking at 24 weeks
- 95% confidence interval
- Not extracted
- Follow-up
- 48 weeks
- Adverse events
- Dose-related GI events; dose-dependent heart-rate increase.
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Sex distribution
- 48.2% female
- Bmi min
- 30
- Obesity status
- obesity or overweight with comorbidity
- Sample size
- 338
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 338
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- 48 weeks
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- not extracted
- Risk of bias
- not assessed (auto)
- Funding conflicts
- yes
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Eli Lilly
- Industry funded
- Yes
- Manufacturer
- Eli Lilly
- Sponsor role
- Sponsor designed and analysed.
- Author conflicts
- Authors report Eli Lilly relationships; sponsor co-authors.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Eli Lilly
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. Its dose-response relationships with respect to side effects, safety, and efficacy for the treatment of obesity are not known. [METHODS] We conducted a phase 2, double-blind, randomized, placebo-controlled trial involving adults who had a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 30 or higher or who had a BMI of 27 to less than 30 plus at least one weight-related condition. Participants were randomly assigned in a 2:1:1:1:1:2:2 ratio to receive subcutaneous retatrutide (1 mg, 4 mg [initial dose, 2 mg], 4 mg [initial dose, 4 mg], 8 mg [initial dose, 2 mg], 8 mg [initial dose, 4 mg], or 12 mg [initial dose, 2 mg]) or placebo once weekly for 48 weeks. The primary end point was the percentage change in body weight from baseline to 24 weeks. Secondary end points included the percentage change in body weight from baseline to 48 weeks and a weight reduction of 5% or more, 10% or more, or 15% or more. Safety was also assessed. [RESULTS] We enrolled 338 adults, 51.8% of whom were men. The least-squares mean percentage change in body weight at 24 weeks in the retatrutide groups was -7.2% in the 1-mg group, -12.9% in the combined 4-mg group, -17.3% in the combined 8-mg group, and -17.5% in the 12-mg group, as compared with -1.6% in the placebo group. At 48 weeks, the least-squares mean percentage change in the retatrutide groups was -8.7% in the 1-mg group, -17.1% in the combined 4-mg group, -22.8% in the combined 8-mg group, and -24.2% in the 12-mg group, as compared with -2.1% in the placebo group. At 48 weeks, a weight reduction of 5% or more, 10% or more, and 15% or more had occurred in 92%, 75%, and 60%, respectively, of the participants who received 4 mg of retatrutide; 100%, 91%, and 75% of those who received 8 mg; 100%, 93%, and 83% of those who received 12 mg; and 27%, 9%, and 2% of those who received placebo. The most common adverse events in the retatrutide groups were gastrointestinal; these events were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose (2 mg vs. 4 mg). Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter. [CONCLUSIONS] In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT04881760.).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 37366315 first ingestion |