A Master Protocol for Orforglipron in Participants With Obstructive Sleep Apnea and Obesity or Overweight

What Was Tested

In this phase 3 trial, researchers set out to test Orforglipron (Foundayo, non-peptide) for sleep apnea (obstructive).

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.

It had two arms (groups): Orforglipron (experimental) and Placebo (placebo comparator).

Participants will receive orforglipron orally. Study 1 GZ01: Participants who are unable or unwilling to use PAP Study 2 GZ02: Participants who plan to continue PAP therapy.

Participants will receive placebo orally. Study 1 GZ01: Participants who are unable or unwilling to use PAP Study 2 GZ02: Participants who plan to continue PAP therapy.

The registry classes the interventions as drug.

Who Took Part

Enrollment: 712 actual participants took part.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Have AHI ≥15 on PSG as part of the trial at screening (V1). Have body mass index (BMI) ≥27 kg/m². Participants who are unable or unwilling to use PAP therapy. Participants must not have used PAP for at least 4 weeks prior to screening. Participants who have been on PAP therapy for at least 3 consecutive months prior to study start and plan to continue PAP therapy during the study.

The full record lists 5 inclusion and 13 exclusion criteria; among the exclusions: have type 1 diabetes (t1d) or type 2 diabetes (t2d), history of ketoacidosis, or hyperosmolar state/coma; had any previous or planned upper airway surgery for sleep apnea or major ear, nose or throat surgery; diagnosis of obesity hypoventilation syndrome or daytime hypercapnia.

How the Study Was Run

Design: randomized, parallel-group and double-blind.

Because people in this Orforglipron (Foundayo, non-peptide) study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

Groups ran in parallel: each of the sleep apnea (obstructive) participants stayed in one arm throughout.

Blinding on both sides kept the sleep apnea (obstructive) participants and researchers unaware of who received Orforglipron (Foundayo, non-peptide).

Those kept unaware of assignments: participant and investigator.

It started in 2024-10-22 with completion listed for 2026-07-21.

It ran at 66 sites in United States (15), China (11), Argentina (8), Germany (8), Mexico (7) and Brazil (5).

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Change from Baseline in Apnea-Hypopnea Index (AHI) (time frame: Baseline to Week 52).

It also tracked 7 secondary outcomes, for example Percent Change from Baseline in AHI, Change from Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% min/hour), Change from Baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a T-score, Percent of Participants with AHI<5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10, Percent Change from Baseline in Body Weight and Change from Baseline in high-sensitivity C reactive protein (hsCRP) Concentration.

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Orforglipron (Foundayo, non-peptide) in 712 people with sleep apnea (obstructive).

With 712 participants it is a large trial for this field.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Orforglipron (Foundayo, non-peptide) compound page, Sleep apnea (obstructive) research.