Evaluating a new treatment approach for obstructive sleep apnoea in adults with obesity and without diabetes: a proof-of-concept study investigating the effects of glucagon-like-peptide-1 agonist-mediated weight loss versus CPAP or both in combination, on metabolic, cardiovascular and quality of life outcomes

Obstructive sleep apnoea (OSA) is independently associated with an increased risk of metabolic complications and cardiovascular disease, as well as impacting on quality of life. Continuous positive airway pressure (CPAP) is the treatment of choice for OSA, but its benefit on the cardiometabolic sequelae of OSA is uncertain. Weight loss in combination with CPAP therapy is superior in improving metabolic outcomes, however weight loss is difficult to achieve and maintain. A weight loss regimen incorporating the glucagon-like peptide-1 (GLP-1) receptor analogue (RA) Liraglutide is superior to conventional weight loss and furthermore, exhibits anti-inflammatory properties. Thus, Liraglutide combined with CPAP may be superior to either treatment alone for OSA-related metabolic dysfunction and cardiovascular disease processes. The aim of the study was to perform a pilot trial to test this hypothesis and to assist in the planning of further randomized controlled trials. These are data from a randomized proof-of-concept study (clinicaltrials.gov: NCT04186494). 30 patients with moderate to severe OSA without diabetes and with a body mass index (BMI) between 30-40kg/m2 were randomised to CPAP, Liraglutide alone or both in combination for 24 weeks. The primary endpoint of the study was the change in HOMA-IR at 24 weeks, secondary endpoints included 24-week changes in weight, OSA severity, glucose tolerance, circulating inflammatory markers, 24 hour BP profile, coronary artery plaque volume as measured by CT coronary angiogram, vascular inflammation measured by FDG-PET CT and change in quality of life. There were no significant differences between groups in baseline characteristics. At study-end, those on Liraglutide alone had the greatest weight loss and improvement in insulin resistance, as well as reductions in blood pressure and some improvement in OSA parameters. CPAP effectively treated OSA, and only subjects on CPAP had a significant decrease in vascular inflammation accompanied by a similar improvement in low-density coronary artery plaque. Combination therapy appeared superior to either treatment alone in improving HbA1c and glycaemia, and patients on combination therapy patients also had improvements in insulin resistance, vascular inflammation, and coronary artery plaque. In conclusion, Liraglutide alone and in combination with CPAP has beneficial effects on metabolic function, weight and OSA, while CPAP improves early atherosclerotic processes. The combination of CPAP and a GLP-1 RA warrants further investigation in larger trials.