The study is a multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III clinical trial to evaluate the efficacy and safety of GZR18 injection in Chinese adult obese patients with moderate-to-severe obstructive sleep apnea (OSA) who are currently using positive airway pressure (PAP) therapy. This study will assess the impact of GZR18 on OSA-related symptoms, respiratory parameters, and quality of life compared to placebo.

Inclusion Criteria:

1. Subject is aged ≥18 years at the time of signing the informed consent form.

2. Body mass index (BMI) is ≥28 kg/m² at both screening and randomization.

3. Subject has a documented history of at least one unsuccessful attempt at weight loss through dietary control prior to screening, and has had <5% change in body weight during the 12 weeks prior to screening (see Appendix 2 for the weight change calculation formula).

4. Subject has been diagnosed with obstructive sleep apnea (OSA) according to the International Classification of Sleep Disorders, 3rd Edition (ICSD-3) criteria prior to screening, and has a centrally assessed apnea-hypopnea index (AHI) ≥15 events/hour on polysomnography (PSG) at screening. (See Appendix 3 for ICSD-3 diagnostic criteria for adult OSA.)

5. Subject has been receiving continuous positive airway pressure (PAP) therapy for at least 12 consecutive weeks prior to screening and intends to continue PAP therapy throughout the study period.

6. Subjects of childbearing potential must agree to remain abstinent or use highly effective contraception from the time of signing informed consent until 8 weeks after the last dose of investigational product, and must not donate sperm or oocytes during this period. Female subjects of childbearing potential must not be lactating and must have a negative pregnancy test at both screening and randomization.

7. The subject fully understands the purpose, nature, methods, and potential adverse reactions of the trial; is able to communicate effectively with the investigator; comprehends and agrees to comply with all study requirements; and voluntarily signs the informed consent form to participate in this study.

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Exclusion Criteria:

1. Known or suspected hypersensitivity to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or any of their excipients, or presence of a contraindication to GLP-1 RA use.
2. History of any type of diabetes mellitus (history of gestational diabetes is permitted).
3. Has undergone or plans to undergo during the study period surgical or device-based obesity treatment (exceptions: acupuncture, liposuction, or abdominal fat removal performed >1 year prior to screening; prior device-based obesity treatment is acceptable if the device was removed >1 year before screening).
4. Secondary obesity due to disease, medication, or other causes (e.g., Cushing's syndrome, Prader-Willi syndrome, monogenic obesity, or obesity secondary to hypothalamic/pituitary injury).
5. Clinically significant gastric emptying disorders at screening (e.g., gastroparesis or gastric outlet obstruction); or long-term use (≥4 consecutive weeks) of medications affecting gastrointestinal motility within 6 months prior to screening.
6. History of acute or chronic pancreatitis or pancreatic injury prior to screening.
7. History of symptomatic gallbladder disease at screening (post-cholecystectomy status is permitted); or presence at screening of cholelithiasis conferring high risk for acute biliary pancreatitis.
8. Clinical or subclinical thyrotoxicosis at screening, regardless of treatment status.
9. Inadequately controlled blood pressure at screening or randomization: systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg (concurrent antihypertensive therapy is permitted).
10. History within 6 months prior to screening of: decompensated heart failure (NYHA Class III-IV), unstable angina, myocardial infarction, ischemic or hemorrhagic stroke (lacunar infarcts excluded), transient ischemic attack; or invasive cardiovascular procedures/therapies (e.g., valve replacement, CABG, PCI). (Diagnostic coronary angiography without intervention is permitted.)
11. Positive response on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening Version to Question 4 or 5 of the "Suicidal Ideation" section, or any question in the "Suicidal Behavior" section, with the event occurring within 4 weeks prior to screening; or investigator assessment of significant suicide risk during the study.
12. History of moderate-to-severe depression; or Patient Health Questionnaire-9 (PHQ-9) score ≥15 at screening.
13. Any uncontrolled acute or chronic hepatitis other than metabolic dysfunction-associated fatty liver disease (MAFLD).
14. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia (MEN) type 2A or 2B.
15. History of malignancy within 5 years prior to screening (exceptions: definitively cured in situ carcinomas, e.g., basal/squamous cell skin cancer, cervical in situ carcinoma, or prostate in situ carcinoma).