TRIUMPH-2: Phase 3 Weight Management in Type 2 Diabetes

Study Overview

TRIUMPH-2 is a Phase 3 clinical trial evaluating retatrutide for weight management in adults with obesity or overweight (BMI ≥27) who also have type 2 diabetes. Alongside TRIUMPH-1 (the core obesity trial without T2D), TRIUMPH-2 is a central component of Eli Lilly’s regulatory submission strategy. The trial includes a nested obstructive sleep apnea (OSA) basket to evaluate the effect of weight loss on sleep-disordered breathing in this population.

TRIUMPH-2 is expected to enroll approximately 1,000 participants globally.

Trial Design

Study Type

TRIUMPH-2 is a randomized, double-blind, placebo-controlled, multicenter, international trial.

Participant Population

• Adults with obesity or overweight (BMI ≥27 kg/m²) AND type 2 diabetes
• Nested OSA basket: subset of participants with documented obstructive sleep apnea
• Expected enrollment of approximately 1,000 participants
• Global enrollment for demographic and geographic diversity

Dose Selection

TRIUMPH-2 evaluates three dose levels of retatrutide:

• 4 mg once weekly
• 9 mg once weekly
• 12 mg once weekly

All doses use a structured escalation protocol (five-step titration) to optimize tolerability, starting at lower doses and gradually increasing to the target maintenance dose over several weeks.

Endpoints

Primary endpoints:

• Percent change in body weight from baseline (main population)
• Change in apnea-hypopnea index (AHI) from baseline (OSA basket)

Expected secondary endpoints:

• Proportion of participants achieving ≥5%, ≥10%, ≥15% weight loss thresholds
• Change in HbA1c from baseline
• Proportion of participants achieving HbA1c <7.0% and <5.7%
• Fasting plasma glucose changes
• Changes in cardiometabolic parameters (blood pressure, lipids)
• Liver fat content (in imaging substudy)
• Safety and tolerability, including hypoglycemia rates

Context from Phase 2

The Phase 2 type 2 diabetes trial provided a strong foundation for TRIUMPH-2:

• Weight loss: Up to -16.9% at 12 mg/36 weeks, substantial for a diabetes population
• HbA1c reduction: Up to -2.02% at 12 mg, with 95% of participants achieving <7.0% and ~62% achieving <5.7%
• Active comparator data: Retatrutide at 8 mg and 12 mg (Phase 2 doses) significantly outperformed dulaglutide 1.5 mg
• Safety: Consistent incretin-class GI profile; low hypoglycemia rates

Key Questions TRIUMPH-2 Will Address

Weight Management in the T2D Population

The primary focus of TRIUMPH-2 is weight management in adults who have both obesity and type 2 diabetes. This population often experiences attenuated weight loss with anti-obesity medications compared to patients without diabetes. TRIUMPH-2 will establish whether retatrutide’s triple agonism can overcome this attenuation and deliver clinically meaningful weight loss in this harder-to-treat group.

OSA Improvement

The nested OSA basket is designed to evaluate whether retatrutide-induced weight loss translates into improvements in obstructive sleep apnea severity. OSA is highly prevalent in the obesity-plus-T2D population, and a positive signal here would broaden retatrutide’s clinical value. The primary OSA endpoint is change in AHI from baseline.

Glycemic Benefits

While the primary endpoint is weight loss (not glycemic control — the TRANSCEND program addresses the standalone T2D indication), TRIUMPH-2 will capture HbA1c and other glycemic parameters as secondary endpoints, providing important data on the combined metabolic benefits of retatrutide in this population.

Safety at Scale

The larger Phase 3 population will provide greater sensitivity for detecting uncommon adverse events and will generate more robust data on hypoglycemia rates, pancreatic safety, thyroid safety, and other monitoring parameters in the diabetes population specifically.

Significance

If TRIUMPH-2 confirms that retatrutide produces substantial weight loss and metabolic improvement in adults with co-existing obesity and type 2 diabetes, it would strengthen the overall regulatory submission by demonstrating efficacy across a broader patient population. The OSA basket adds further clinical relevance, potentially supporting a comorbidity-specific benefit claim. Combined with TRIUMPH-1 (obesity without T2D) and TRIUMPH-4 (obesity with knee OA), TRIUMPH-2 rounds out the evidence base across key obesity subpopulations.

Timeline

• Enrollment: Ongoing
• Treatment period: 68-72 weeks estimated
• Primary results: Expected 2026
• Regulatory implications: TRIUMPH-2 data, combined with TRIUMPH-1, will form the basis for regulatory submission for the weight management indication in the T2D population