BACKGROUND: Obstructive sleep apnea (OSA) is a chronic condition that is associated with significant morbidity and mortality. Positive airway pressure (PAP) therapy is the gold-standard treatment for OSA but has low adherence rates. Observational studies, including post-hoc analyses of clinical trials, suggest an association between treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) and reduction in incident or diminished severity of prevalent OSA. However, the effects of SGLT2i therapy on the clinical severity of OSA and its mechanistic relation to underlying OSA pathophysiology have not been tested in a randomized clinical trial.
METHODS AND RESULTS: The Adipose Dysfunction, Imaging, Physiology, and Outcomes with SGLT2i's for Sleep Apnea (ADIPOSA) study is a double-blind, randomized, placebo-controlled clinical trial that will enroll 164 patients with overweight/obesity and moderate to severe OSA across two sites (Cleveland, OH and New Haven, CT). All participants will complete medical history and sleep questionnaires and undergo ambulatory polysomnography, neck and body fat imaging, 7-day actigraphy, 24-h ambulatory blood pressure monitoring, and a blood draw at baseline and 6-month follow-up. Patients will be randomized 1:1 to receive either bexagliflozin 20 mg once daily or a matching placebo. The primary outcome is a reduction in the apnea-hypopnea index, and secondary outcomes include changes in sleep health, body fat distribution, blood pressure, activity, and biomarkers of inflammation and metabolism.
CONCLUSIONS: The ADIPOSA study will identify the mechanisms underlying the effects of SGLT2i on OSA while providing evidence for future investigation to test the efficacy of pharmacologic SGLT2i on OSA prevention and treatment.
