TRIUMPH-5: Obesity with Obstructive Sleep Apnea

Study Overview

TRIUMPH-5 evaluates retatrutide in adults with obesity and moderate-to-severe obstructive sleep apnea (OSA). OSA affects approximately 936 million adults worldwide and is strongly associated with obesity — excess weight in the neck and pharyngeal area directly contributes to airway obstruction during sleep.

Scientific Rationale

Obesity-OSA Connection

The relationship between obesity and OSA is bidirectional:

• Obesity causes OSA: Fat deposition in the pharyngeal area reduces airway caliber; abdominal obesity decreases lung volume
• OSA worsens obesity: Sleep fragmentation disrupts appetite hormones (leptin, ghrelin), promotes insulin resistance, and reduces physical activity

Weight Loss and OSA

Weight loss is the most effective non-surgical treatment for OSA:

• A 10% weight loss typically reduces AHI by 26-32%
• The STEP 2 trial with semaglutide showed significant AHI improvement
• Tirzepatide demonstrated OSA benefits in the SURMOUNT-OSA trial
• Retatrutide’s greater weight loss magnitude could provide superior AHI reduction

Study Design

Population

Adults aged 18-75 with:

• BMI ≥30 kg/m²
• Moderate-to-severe OSA (AHI ≥15 events/hour by polysomnography)
• Currently using or candidates for CPAP therapy

Endpoints

Co-primary endpoints:

• Percent change in body weight at the primary assessment timepoint
• Change in AHI from baseline

Key secondary endpoints:

• Proportion achieving AHI <5 (OSA resolution)
• Oxygen desaturation index change
• CPAP pressure requirements
• Epworth Sleepiness Scale improvement
• Quality of life measures

Expected Outcomes

Based on the Phase 2 weight loss data and the relationship between weight loss and AHI:

• 20-25% weight loss could reduce AHI by 50-70%
• A significant proportion of patients may achieve AHI <15 (below moderate threshold)
• Some patients may achieve complete OSA resolution (AHI <5)

Competitive Context

• Tirzepatide SURMOUNT-OSA: Demonstrated AHI reduction of ~50% with ~18% weight loss
• Semaglutide: Showed modest AHI improvements
• Retatrutide advantage: Greater weight loss could translate to greater AHI improvement