Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder, as people with OSA repeatedly stop and start breathing while they sleep. OSA is a significant risk factor for a variety of cardiovascular diseases, the conditions that affect your heart and blood vessels. Moreover, OSA and type 2 diabetes (a condition that causes the level of glucose in the blood to become too high) frequently occur together that further increase the risk for cardiovascular disease. Obesity remains the main modifiable risk factor for OSA. New anti-diabetic drugs (glucagon-like peptide 1 receptor (GLP-1 RA) agonists) have been developed for type 2 diabetes, and have shown significant efficacy in reducing the risk of cardiovascular disease in patients with type 2 diabetes, as well as significantly reducing body weight. We therefore hypothesize that GLP-1 RAs might be efficient to prevent the development of OSA and its severity.
This study will use the Clinical Practice Research Datalink to determine whether the use of GLP-1 RAs is associated with a reduced risk of developing OSA and discontinuing treatment for OSA (such as continuous positive airway pressure, a device that uses positive pressure to keep the airway open during sleep) compared with DPP4 inhibitors (another class of anti-diabetic drugs), in two cohorts of adult individuals between 2007 and 2023.
If confirmed, this study will help inform clinicians about the potential efficacy of GLP-1 RAs to prevent and treat OSA for patients in England and Wales.
Obstructive sleep apnoea (OSA) affects nearly one billion middle-aged individuals worldwide, with a rising prevalence reflecting the increasing prevalence of overweight and obese people. OSA is a significant risk factor for a variety of cardiovascular diseases, including hypertension, coronary heart disease, stroke and arrhythmias. Furthermore, OSA and type 2 diabetes frequently occur together, and both are associated with adverse metabolic consequences that further increase the risk for cardiovascular disease.
Glucagon-like peptide 1 receptors agonists (GLP-1 RAs) were developed as glucose-lowering agents for type 2 diabetes by targeting the incretin pathway, and demonstrated meaningful weight loss in trials of patients with and without type 2 diabetes. Several small non-placebo-controlled studies have suggested a beneficial impact of GLP-1 RAs on OSA, and OSA has been found to be associated with elevated serum levels of the incretin hormones GLP-1 and GIP in patients without diabetes.
he primary objectives of this study will be to assess the effectiveness of GLP-1 RAs to prevent OSA and to improve OSA in patients treated by continuous positive airway pressure (defined as a treatment discontinuation), compared to DPP4 inhibitors use, in two cohorts of patients>18 years of age between 1 January 2007 and 31 December 2023.
We will use an active comparator new user cohort design using the CPRD Aurum Database. The outcomes will be first diagnosis of OSA in the first cohort and discontinuation of CPAP in the second cohort. Subjects exposed to GLP-1 RAs will be matched 1:1 to exposed subjects to DPP4 inhibitors based on time-dependent propensity scores.
The hazard ratios (HR) and corresponding 95% confidence intervals (CI) of the outcomes with GLP-1 RAs use versus DPP4 inhibitors will be estimated using Cox proportional hazards regression models.
Sleep apnoea diagnosis or treatment.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Charles Khouri - Collaborator - McGill University
Laurent Azoulay - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University