The Future of Obstructive Sleep Apnea Treatment: A Paradigm Shift?

Article information

Sleep Med Res. 2025;16(2):81-83

Publication date (electronic) : 2025 June 26

doi : https://doi.org/10.17241/smr.2025.02908

Ji Ho Choi, MD, PhD

Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Korea

Corresponding Author Ji Ho Choi, MD, PhD Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon 14584, Korea Tel +82-32-621-5015 Fax +82-32-621-5016 E-mail handsomemd@hanmail.net

Received 2025 May 6; Accepted 2025 June 17.

Obstructive sleep apnea (OSA) is a prevalent and increasingly recognized sleep disorder characterized by repetitive upper airway collapse during sleep, resulting in intermittent hypoxia, arousals, and disrupted sleep architecture [1]. It is associated with significant health consequences, including cardiovascular disease, metabolic dysfunction, cognitive impairment, and diminished quality of life. Thus, prompt diagnosis is needed for OSA [2]. Currently, various therapeutic modalities are employed in the clinical management of OSA, including positive airway pressure (PAP), oral appliances, surgery, positional therapy, and weight management [3]. Of these, PAP, oral appliances, and surgical interventions have conventionally been the primary modalities used for managing this condition. While these methods have demonstrated clinical efficacy, their real-world adherence and treatment success rates often remain suboptimal [4-6]. Specifically, PAP and oral appliance therapy are frequently discontinued due to discomfort or side effects, while surgical interventions inherently carry risks with difficulty to predict their success [4-6]. In recent years, there has been growing interest in emerging therapies that aim to improve outcomes by targeting the underlying pathophysiology of OSA such as obesity and neuromuscular dysfunction or by enhancing patient adherence through less invasive interventions [7-9]. These novel interventions, including anti-obesity medications, pharmacologic agents targeting muscle responsiveness, and hypoglossal nerve stimulation (HGNS) therapies, raise an important clinical question: Will the OSA treatment paradigm shift?

PAP remains the gold standard treatment for moderate to severe OSA [10]. It works by delivering a constant stream of air to maintain airway patency throughout the night. Numerous studies have shown its effectiveness in reducing the apnea-hypopnea index (AHI), improving oxygenation, and decreasing cardiovascular risk [4]. Despite its efficacy, its adherence rates hover around 40%–80% largely due to discomfort, mask-related issues, noise, or claustrophobia [4]. Patients often discontinue its use within the first few weeks, limiting its real-world effectiveness. Oral appliances, typically mandibular advancement devices, are also established treatment, especially for patients with mild to moderate OSA or those intolerant to PAP [10]. These devices can improve OSA by repositioning the lower jaw forward. They can also enhance upper airway muscle tone, both of which can stabilize the airway and prevent collapse during sleep. Although these devices are less effective than PAP in reducing AHI, they have higher adherence rates and tolerance [5,10]. However, their use can be limited by temporomandibular joint discomfort, dental changes, and/or lack of efficacy in severe OSA [5]. Conventional surgical options including oropharyngeal surgery (e.g., uvulopalatopharyngoplasty), hypopharyngeal surgery (e.g., tongue base reduction), and nasal surgeries aim to reduce upper airway obstruction anatomically [10]. Although these can be effective for select patients, they are associated with variability in outcomes and the risk of postoperative complications [6,10]. In addition, many patients are reluctant to undergo invasive procedures. Furthermore, surgeries are not always curative, especially in the context of multifactorial airway collapse [6,10].

Given that obesity is a major risk factor for OSA, pharmacologic agents targeting weight loss have emerged as a logical therapeutic strategy. Recent medications such as GLP-1 receptor agonists (e.g., tirzepatide, liraglutide, etc.) have demonstrated significant weight reduction and potential improvements in OSA severity [7,11]. Weight loss not only can reduce AHI, but also can improve metabolic health and cardiovascular risk. Anti-obesity medications hold promise as less invasive and more accessible alternatives for select OSA patients such as overweight or obese patients with OSA. However, their clinical utility depends on robust long-term data to inform patient selection and integration into comprehensive treatment strategies.

Multiple clinical trials investigating combinations such as atomoxetine and oxybutynin/aroxybutynin have demonstrated that they can improve OSA [8,12,13]. These compounds can enhance upper airway muscle responsiveness in OSA patients by increasing norepinephrine levels via atomoxetine and reducing cholinergic inhibition through oxybutynin/aroxybutynin, thereby improving genioglossus muscle tone and stabilizing the pharyngeal airway during sleep [8,12,13]. Although their long-term efficacy, safety, and optimal patient selection still require further research, they represent a significant step towards precision medicine in OSA treatment. Future pharmacotherapy targeting muscle responsiveness might offer a tailored alternative for patients with specific endotypic traits such as impaired upper airway muscle tone. As research advances, these agents could become key components of personalized OSA management strategies, complementing or replacing conventional therapies in select populations.

HGNS represents a significant advancement in neuromodulation therapy for OSA, with various companies now developing and offering their own HGNS systems (e.g., Inspire, LivaNova, Nyxoah) [9,14,15]. These devices can stimulate the hypoglossal nerve to promote tongue protrusion and maintain upper airway patency during sleep. Clinical trials have demonstrated that HGNS can improve AHI and quality of life, particularly among patients with moderate to severe OSA who are intolerant of PAP therapy [9,14,15]. While HGNS offers an effective, maskfree alternative, it has limitations, including high cost, the requirement for surgical implantation, and strict eligibility criteria (e.g., for Inspire, patients should not be significantly obese and must not exhibit complete concentric collapse on drug-induced sleep endoscopy) [9]. Long-term durability and broader accessibility of this therapy remain under active investigation.

In conclusion, while conventional managements—especially PAP therapy—remain the mainstay of OSA treatment due to their proven efficacy and clinical familiarity, emerging therapies are rapidly gaining traction. Limitations of current options in terms of adherence and tolerability underscore the need for innovation. As medical science and technology continue to evolve, therapies such as weight-loss medications, pharmacological agents, and nerve stimulation devices might provide more personalized, effective, and acceptable treatment alternatives. In the future, a more individualized and multi-modal approach combining conventional and emerging therapies might redefine the landscape of OSA management, ultimately improving outcomes and quality of life for a broader spectrum of patients.