Emerging treatments

Atomoxetine plus oxybutynin

Combination therapy with atomoxetine (a selective noradrenaline-reuptake inhibitor) plus oxybutynin significantly improved OSA severity in patients with moderate pharyngeal collapsibility in a phase 2, randomised, placebo-controlled crossover study.[204] The presumptive mechanism is enhanced genioglossus responsiveness.[205] Phase 2, randomised, double-blind, placebo-controlled trials report short-term improvement of OSA among patients who received atomoxetine plus aroxybutynin (an [R]-isomer of oxybutynin).[206][207]

Novel implantable hypoglossal neurostimulation systems

Include systems that do not require a respiratory sensor (aura6000), instead using selective, cyclical, near tonic stimulation of the hypoglossal nerve’s trunk via multiple contacts. Drug-induced sleep endoscopy (DISE) is not needed for patient selection. AHI and oxygen desaturation index (ODI) reduction of 52% and 62%, and clinical improvement in sleepiness and quality of life have been demonstrated in a randomised-controlled trial (RCT).[208] An additional system (Genio) utilises an implantable receiver that stimulates the terminal hypoglossal nerve to the genioglossus muscles bilaterally. This system is unique in that the pulse generator is external, applied to the skin on a patch. In a case series of 22 patients, significant AHI and ODI reduction, and improvement in quality of life, was reported after 6 months.[209] Clinical trials are recruiting or ongoing.[210][211]​​​​

Ansa cervicalis co-stimulation

Co-stimulation of the ansa cervicalis nerve with hypoglossal nerve stimulation resulted in a greater benefit than hypoglossal neurostimulation alone, in one small study.[212] The mechanism may be longitudinal stabilisation of the upper airway. Further trials are recruiting.[213]

Pharmacotherapy for concurrent obesity

Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, increases insulin secretion, suppresses glucagon secretion, and slows gastric emptying. In one RCT in moderate-to-severely obese OSA patients, liraglutide (as adjunct to diet and exercise) significantly reduced AHI, body weight, systemic blood pressure, and HbA1c compared with placebo.[214] Liraglutide was generally well tolerated. One small trial to investigate the effect of liraglutide on cardiometabolic outcomes in patients with OSA is ongoing.[215]

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