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

Clinical Trial29 Sept 2025Phase 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

View original source ↗

Related signals

Strategic Signal

FDA1 Apr 2026New Drug Approval (NDA/BLA)High impact● 10/10i

FDA Approves Foundayo (Orforglipron) — New Drug Approval (NDA/BLA)

FDA approved orforglipron (Foundayo, Eli Lilly) for type 2 diabetes -- a once-daily oral small-molecule GLP-1 receptor agonist. Orforglipron is the first non-peptide oral GLP-1 approved in the US; oral semaglutide (Rybelsus, Novo Nordisk) has been approved for T2D since 2019 and expanded to obesity in January 2026. Unlike Rybelsus, orforglipron requires no fasting or water volume restrictions before dosing.

GLP-1Type 2 diabetesPricing/accessEli Lilly Novo Nordisk

Strategic Signal

Clinical Trial19 Mar 2026Phase 3High impact● 9/10i

Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)

Phase 3 SURMOUNT-1 tests once-weekly tirzepatide at three doses versus placebo in adults without type 2 diabetes who have obesity or are overweight with comorbidities. The randomized, double-blind trial targets 2,539 participants with primary efficacy assessment at 72 weeks. This represents tirzepatide's pivotal obesity trial against placebo, potentially supporting Eli Lilly's bid to compete directly with Wegovy in the non-diabetic obesity market. A prediabetes subgroup continues long-term to assess diabetes prevention.

Weight lossGLP-1Eli Lilly

Strategic Signal

FDA19 Mar 2026Supplemental Approval: Efficacy [Priority Review]High impact● 9/10i

FDA Approves Imcivree (Setmelanotide): Supplemental Approval: Efficacy [Priority Review]

FDA approved a supplemental application for Imcivree (setmelanotide, Rhythm) on March 19, 2026, under priority review. This represents an efficacy-based label expansion for the melanocortin-4 receptor agonist, which was initially approved for rare genetic obesity disorders. Rhythm gains additional indication breadth in the specialized rare obesity market, where treatment options remain extremely limited. The priority review designation signals FDA recognition of significant unmet medical need in the expanded patient population.

Weight lossOtherRhythm

Strategic Signal

Clinical Trial17 Apr 2026Phase 3High impact● 8/10i

A Phase 3, Open-Label Study of Once Daily LY3502970 Compared With Insulin Glargine in Adult Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk

Phase 3 open-label trial compared once-daily oral orforglipron versus insulin glargine in people with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study enrolled 2,749 participants with primary endpoint of time to first major adverse cardiovascular event, completed in March 2026. Eli Lilly is positioning orforglipron as a cardiovascular outcomes option in high-risk populations, directly competing with established insulin therapy in this indication. This represents the first cardiovascular outcomes trial for orforglipron following its April 2026 FDA approval for type 2 diabetes.

GLP-1Type 2 diabetesWeight lossCardiovascularEli Lilly