Home › Trials › NCT06649045

Evaluating orforglipron for treating obstructive sleep apnea in overweight or obese patients

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

Phase 3 Interventional Eli Lilly and Company · NCT06649045

This study is testing if a new medication called orforglipron can help overweight or obese people with moderate-to-severe sleep apnea feel better, whether or not they are using a breathing machine.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company Industry-sponsored
Locations78 sites (Long Beach, California and 77 other locations)
Trial IDNCT06649045 on ClinicalTrials.gov

What this trial studies

This clinical trial is designed to assess the efficacy and safety of orforglipron in individuals suffering from moderate-to-severe obstructive sleep apnea (OSA) who are also overweight or obese. The study employs a master protocol that supports two independent studies: one for participants unable or unwilling to use positive airway pressure (PAP) therapy, and another for those currently using PAP therapy. Participants will be randomly assigned to the appropriate study based on their eligibility criteria, which include specific body mass index (BMI) and apnea-hypopnea index (AHI) thresholds.

Who should consider this trial

Good fit: Ideal candidates for this study are adults with a body mass index (BMI) of 27 kg/m² or higher and a diagnosis of moderate-to-severe obstructive sleep apnea.

Not a fit: Patients with Type 1 or Type 2 diabetes, or those who have undergone significant upper airway surgery for sleep apnea, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with OSA who are overweight or obese, particularly those who cannot tolerate traditional PAP therapy.

How similar studies have performed: While this approach is novel in its specific application, similar studies evaluating pharmacological treatments for OSA have shown promise in the past.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

Master GZRA inclusion criteria

* have AHI ≥15 on PSG as part of the trial at screening (V1).
* have body mass index (BMI) ≥27 kg/m²

Study 1 GZ01 inclusion criteria

* Participants who are unable or unwilling to use PAP therapy.
* Participants must not have used PAP for at least 4 weeks prior to screening.

Study 2 GZ02 inclusion criteria

* 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.

Exclusion Criteria:

Master GZRA exclusion criteria

* Have Type 1 diabetes (T1D) or Type 2 diabetes (T2D), history of ketoacidosis, or hyperosmolar state/coma
* Have HbA1c ≥6.5% (≥ 48 mmol/mol), as determined by the central laboratory at Visit 1.
* Had any previous or planned upper airway surgery for sleep apnea or major ear, nose or throat surgery
* Have diagnosis of Central or Mixed Sleep Apnea with % of mixed or central apneas/hypopneas ≥50%, or diagnosis of Cheyne Stokes Respiration
* Diagnosis of Obesity Hypoventilation Syndrome or daytime hypercapnia.
* Active device treatment of OSA other than PAP therapy
* Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator.
* Have a self-reported change in body weight \>5 kg within 3 months prior to screening
* Have a prior or planned surgical treatment for obesity (excluding liposuction, abdominoplasty or cryolipolysis if performed more than 1 year prior to screening)
* Have a prior or planned endoscopic and/or present device-based therapy for obesity.
* Have obesity induced by other endocrinologic disorders or diagnosed monogenetic or syndromic forms of obesity.

Study 2 GZ02 exclusion criteria

* Have personal or job-related responsibilities, or in the opinion of the investigator have any situation that would make it unsafe to stop PAP therapy for 7 days prior to PSG testing during the study.
* Are unwilling to temporary discontinue PAP therapy for 7 days prior to PSG testing during the study.

Where this trial is running

Long Beach, California and 77 other locations

+28 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions OSAOverweight or Obesity
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.