Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea

Inclusion Criteria:

For GPI1 Participants:

• Participants who are unable or unwilling to use PAP therapy. Participants must nothave used PAP for at least 4 weeks prior to screening.

For GPI2 Participants:

• Have been on PAP therapy for at least 3 consecutive months prior to screening andplan to continue PAP therapy during the study

For Both GPI1 and GPI2 Participants:

• Have an AHI ≥15 on PSG as part of the trial at screening

• Have a body mass index (BMI) ≥30 kilogram/square meter (kg/m²)

• Have a history of at least 1 self-reported unsuccessful dietary effort to lose bodyweight

Exclusion Criteria:

For GPI2 Participants:

• 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 priorto PSG testing during the course of the study

• Are unwilling to stop PAP therapy for 7 days prior to polysomnography (PSG) testingduring the course of the study

For GPI1 and GPI2 Participants:

• Female participants must not be pregnant, intending to be pregnant, breastfeeding,or intending to breastfeed.

• Have type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), history ofketoacidosis, or hyperosmolar state/coma.

• Have HbA1c ≥ 6.5% (≥ 48 mmol/mol) at baseline

• Any previous or planned surgery for sleep apnea or major ear, nose or throatsurgery, including tonsillectomy and adenoidectomy that still may affect breathingat time of baseline

• Have significant craniofacial abnormalities that may affect breathing at baseline

• 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 (for example, dentalappliance), or other treatment, that in the opinion of the investigator, mayinterfere with study outcomes, unless willing to stop treatment at baseline andthroughout the study.

• 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 orabdominoplasty if performed more than 1 year prior to screening)

• Have or plan to have endoscopic and/or device-based therapy for obesity or have haddevice removal within the last 6 months (for example, mucosal ablation, gastricartery embolization, intragastric balloon, and duodenal-jejunal bypass sleeve)