TRIUMPH-3
TRIUMPH-3: Weight Management Maintenance Trial
Phase 3 trial evaluating retatrutide for weight management maintenance — assessing whether weight loss can be sustained long-term and the effects of treatment withdrawal.
TRIUMPH-3 — Phase 3 trial evaluating retatrutide for weight management maintenance — assessing whether weight loss can be sustained long-term and the effects of treatment withdrawal.
Trial Facts
| Property | Value |
|---|---|
| Trial Name | TRIUMPH-3 |
| Phase | 3 |
| Status | ongoing |
| Enrollment | 1,400 participants |
| Start Date | February 1, 2024 |
| Conditions | obesity, weight management |
Study Overview
TRIUMPH-3 addresses one of the most critical questions in obesity pharmacotherapy: can weight loss be maintained long-term, and what happens when treatment is stopped? Weight regain after discontinuation has been a limitation of all currently approved obesity medications, and this trial will provide direct evidence on retatrutide’s durability profile.
Scientific Rationale
The Weight Regain Problem
Clinical data from other GLP-1 receptor agonists has shown significant weight regain after treatment discontinuation:
- Semaglutide (STEP 1 extension): Approximately two-thirds of weight lost was regained within 1 year of stopping treatment
- Tirzepatide (SURMOUNT-4): Participants who switched to placebo regained approximately 14% body weight over 1 year
Understanding retatrutide’s maintenance profile is essential because:
- Chronic treatment may be necessary for sustained benefit
- Payers and health systems need duration-of-treatment data for coverage decisions
- Patients need realistic expectations about long-term weight management
Study Design
TRIUMPH-3 is expected to employ a randomized withdrawal design:
- Run-in phase: All participants receive retatrutide to achieve weight loss
- Randomized phase: Responders are randomized to continue retatrutide or switch to placebo
- Assessment: Weight trajectory is compared between groups
Endpoints
- Percent change in body weight during the maintenance/withdrawal phase
- Proportion maintaining clinically meaningful weight loss thresholds
- Cardiometabolic parameter changes during maintenance vs. withdrawal
- Safety during long-term treatment
Key Questions
- Does the glucagon receptor component affect weight regain kinetics differently than dual or single agonists?
- Are metabolic improvements (blood pressure, lipids, glucose) maintained with continued treatment?
- What is the rate and magnitude of weight regain upon discontinuation?
- Can lower maintenance doses sustain weight loss achieved at higher induction doses?
Sources Used On This Page
- 1eli-lilly-2024
- 2jastreboff-2023-nejm