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

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 tostudy 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, orhyperosmolar state/coma

• Have HbA1c ≥6.5% (≥ 48 mmol/mol), as determined by the central laboratory at Visit

• Had any previous or planned upper airway surgery for sleep apnea or major ear, noseor throat surgery

• Have diagnosis of Central or Mixed Sleep Apnea with % of mixed or centralapneas/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 thetrial 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 orsyndromic forms of obesity.

Study 2 GZ02 exclusion criteria

• Have personal or job-related responsibilities, or in the opinion of the investigatorhave any situation that would make it unsafe to stop PAP therapy for 7 days prior toPSG testing during the study.

• Are unwilling to temporary discontinue PAP therapy for 7 days prior to PSG testingduring the study.