A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants Who Have Obstructive Sleep Apnea and Obesity or Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial

ClinicalTrials29 Sept 2025·Phase 3● 6/10i

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants Who Have Obstructive Sleep Apnea and Obesity or Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial

Eli Lilly and Company

Eli Lilly is testing orforglipron, its oral small-molecule GLP-1, in adults with moderate-to-severe obstructive sleep apnea and obesity or overweight across two parallel studies. The phase 3 master protocol will enroll 600 participants through November 2026, comparing orforglipron to placebo with sleep apnea severity as the primary endpoint. This represents Eli Lilly's move into sleep medicine with orforglipron, targeting an indication where Zepbound recently gained FDA approval in December 2024. The dual-study design separates participants by PAP therapy use, suggesting potential for differentiated positioning across OSA treatment patterns.

Strategic signal

Eli Lilly is building orforglipron's sleep apnea evidence base to compete with tirzepatide's December 2024 FDA approval for OSA in adults with obesity. The master protocol design suggests Lilly sees commercial opportunity across PAP-using and non-PAP populations, potentially enabling broader market access than Zepbound's current positioning. This trial positions orforglipron as Lilly's second OSA asset after Zepbound, creating potential cannibalization risk but also indication diversification for the oral small-molecule platform.

GLP-1Weight lossOtherEli Lilly

Original Abstract

Study GZRA is a master protocol that will support 2 independent studies, GZ01 and GZ02. Participants will be assigned to the appropriate study prior to randomization. The purpose of the studies is to evaluate the efficacy and safety of orforglipron in participants who have moderate-to-severe OSA and obesity or overweight. Study GZ01 will include participants who are unable or are unwilling to use PAP therapy. Study GZ02 will include participants who are on PAP therapy for at least 3 months at time of screening and plan to continue PAP therapy during the study. | Condition(s): OSA; Overweight or Obesity | Primary endpoint(s): Change from Baseline in Apnea-Hypopnea Index (AHI) | Enrollment: 600 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2026-11 | Status: Active Not Recruiting | Last update: 2025-09-29

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