Tirzepatide Versus Positive Airway Pressure for the Treatment of Obstructive Sleep Apnoea: A Randomised Comparative Effectiveness Trial

Inclusion Criteria: * Females and Males aged ≥ 18 years at the time of signing informed consent * Moderate-severe OSA defined as an AHI ≥ 15/hr determined from a Type 1 or 2 sleep study conducted within the previous 12 months with a clinician recommendation for CPAP therapy. * Moderate overweight or obesity defined as BMI ≥ 27 kg/m2. (Adjusted to BMI ≥ 25 kg/m2 for Asian populations as per WHO guidelines (WHO Expert Consultation (2004)) * No contraindication to tirzepatide use as per Australian Product Information * Home internet access to enable cloud storage of SleepTracker-AI in-home BDI. * Fluent English literacy and able to provide informed consent. Exclusion Criteria: OSA or other respiratory related criteria: * Respiratory failure including obesity hypoventilation syndrome (OHS) or daytime hypercapnia or moderate-severe chronic obstructive pulmonary disease (COPD) with FEV1/FVC ratio\<0.7 and FEV1\<80% predicted (GOLD criteria). * Driver occupation with excessive sleepiness (Epworth Sleepiness Scale \>=16) or sleepiness-related motor vehicle accident or near accident within 12 months prior to enrolment * Current or prior (≤3 months) OSA treatment with mechanical therapy (CPAP, MAS, Positional) * \>50% respiratory events with Cheyne-Stokes Respiration (CSR) or Central Sleep Apnoea (CSA) * Relative or absolute contraindication to CPAP including chronic cranial injury; recurrent pneumothorax; indication for oral-pharyngeal surgery, significant craniofacial abnormalities that may affect breathing, or are unwilling to use CPAP * Any previous or planned surgery for OSA or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy that still may affect breathing (NB: Inclusion of a participant with more minor ear, nose or throat surgery (for example, deviated septum) will be at the investigator's discretion) Glycaemia related criteria: * HbA1c ≥ 48 mmol/mol (6.5%) at screening * Type 1 or type 2 diabetes mellitus * Treatment with glucose-lowering agent(s) within 90 days before screening * Treatment with a GLP-1 receptor agonist within 90 days before screening Obesity related criteria: * A self-reported change in body weight \>5 kg or \>5% within 90 days before baseline * Treatment with medication for the indication of obesity within 90 days before baseline and/or currently enrolled in a weight loss program Other criteria: * Pregnancy/breast feeding or planning a pregnancy during the trial period * Relative or absolute contraindication to tirzepatide including needle phobia