Obstructive Sleep Apnoea Treatments—Where Are We Now?

1.

Obstructive sleep apnoea (OSA) affects up to 1 billion adults worldwide [1]. The impact of untreated OSA is well described, contributing to an elevated risk of cardiovascular disease, neurocognitive impairment, motor vehicle accidents, and mortality [2]. Although positive airway pressure (PAP) therapy is the gold standard to treat moderate‐to‐severe OSA, high rates of intolerance limit its clinical applicability. Pharmacological, device‐based, and surgical interventions are reshaping the therapeutic landscape and signal a shift towards precision medicine (Figure 1). However, long‐term outcome data is lacking. This commentary provides an overview of current and emerging OSA treatments.

FIGURE 1.

Emerging treatment options for obstructive sleep apnoea beyond positive airway pressure therapy.

When used as prescribed, PAP therapy reduces OSA severity, daytime sleepiness, and systolic blood pressure [3]. A recent meta‐analysis combining randomised controlled trials (RCTs) and non‐randomised controlled studies reported an association between PAP use and reduced cardiovascular and all‐cause mortality [4]. This should be cautiously interpreted as all RCTs to date have been negative, and non‐randomised studies (which accounted for 80%–95% of the meta‐analysis weight) are vulnerable to biases such as the healthy user effect [5]. Among those who do commence PAP therapy, its use is plagued by poor adherence, and almost half of the patients terminate treatment within 3 years [6]. Despite improvements in mask design, device technology, and behavioural support strategies, adherence rates have stagnated over the past two decades [7]. Discontinuation of PAP therapy, even intermittently, leads to rapid OSA recurrence, with clinical and objective relapses observed within 1 week [8].

Obesity is a major risk factor for OSA, with 39% of people with moderate and 47% with severe OSA having comorbid obesity [9]. In recent years, notable breakthroughs in incretin‐based medications for obesity have had important implications for OSA treatment. In the SURMOUNT‐OSA trial, tirzepatide, a long‐acting glucose‐dependent insulinotropic polypeptide receptor and glucagon‐like peptide‐1 receptor agonist developed for weight loss, significantly reduced the apnoea‐hypopnoea index (AHI), with 48%–60% of study participants achieving OSA resolution [10]. Tirzepatide improved patient‐reported sleep outcomes, excess weight, systolic blood pressure, and markers of inflammation. It also reduced hypoxic burden, a physiologic measure that outperforms AHI in predicting cardiovascular and all‐cause mortality [11]; and in non‐OSA samples, improved various cardiometabolic outcomes [12, 13, 14]. However, uncertainties regarding the feasibility of routine clinical implementation remain. The SURMOUNT‐OSA participants had marked obesity (mean BMI ~39 kg/m²), which limits generalisability to individuals who are only overweight, in whom improvements in OSA severity may be less pronounced. Given the proportional relationship between weight loss and AHI reduction [15], weight regain following tirzepatide withdrawal [16] will likely lead to OSA relapse. Long‐term data on safety, adherence, and efficacy outcomes are therefore essential before incretins can be considered first‐line options or substitutes for PAP therapy in the patient with OSA and obesity.

The pursuit of personalised OSA treatments has been driven by the characterisation of ‘endotypes’ (physiological traits) underlying OSA pathophysiology. Of particular interest in contemporary pharmacotherapy research are four OSA endotypes: high loop gain, reduced arousal threshold, impaired pharyngeal muscle responsiveness, and increased upper airway collapsibility [17]. As PAP therapy only targets airway collapsibility, its failure in some patients may reflect the contribution of untreated endotypes. Proof‐of‐concept studies proposed to target these traits have demonstrated only modest reductions in AHI [18]. A common methodological limitation is the enrolment of participants who were rarely selected based on the specific endotypes the drugs supposedly target. These studies lacked metrics on long‐term efficacy, patient‐reported outcomes, safety, or tolerability to justify routine clinical use. In contrast to the predictable improvement in OSA severity observed with weight loss, improvements in AHI did not correlate with changes in the targeted endotype. In some cases, adverse effects outweighed potential benefits and patient‐reported outcomes worsened on the study drug. Encouragingly, recent press releases from two phase III RCTs (SynAIRgy NCT05813275 and LunAIRo NCT05811247) reported that aroxybutynin‐atomoxetine, theorised to enhance upper airway muscle tone during sleep, achieved its primary endpoint of AHI reduction at 26 weeks [19, 20]. If subsequent data confirm improvements in patient‐reported outcomes, these findings may represent a pivotal step towards endotype‐driven treatments.

Device‐based therapies and surgical treatments offer an alternative for patients who decline or cannot tolerate PAP therapy. For instance, oral appliance therapy, such as mandibular advancement splints (MAS), repositions the mandible anteriorly to maintain upper airway patency during sleep. While less effective than PAP in reducing OSA severity, they yield comparable improvements in daytime sleepiness, blood pressure, simulated driving performance, and disease‐specific quality of life [21, 22]. Uvulopalatopharyngoplasty is the most common surgical approach. Multilevel upper airway surgery, a contemporary uvulopalatopharyngoplasty technique, significantly improves polysomnographic measures of OSA severity, daytime sleepiness, and sleep‐related quality of life, compared to medical management alone [23]. Serious surgery‐related morbidity was rare, and clinical effectiveness was sustained at 3.5 years of follow‐up [24]. Further studies are needed to clarify long‐term effects on cardiovascular outcomes and mortality, and to define patient characteristics that predict benefit. Hypoglossal nerve stimulation has emerged as a promising second‐line therapy, supported by data from the STAR trial and ADHERE global registry demonstrating durable treatment effects and sustained improvements in insomnia, daytime hypersomnolence, quality of life, and depression [25, 26]. However, cardiovascular benefits remain unproven, and broader implementation is limited by high cost, surgical risks, and strict eligibility criteria. As with multilevel upper airway surgery, the influence of phenotypic traits on treatment response is uncertain.

For patients with OSA and residual daytime sleepiness (despite adequate PAP or MAS use), wakefulness‐promoting agents can be valuable adjuncts. Pitolisant, a histamine H3 receptor antagonist and inverse agonist, and solriamfetol, a dopamine‐norepinephrine reuptake inhibitor, have demonstrated wake‐promoting effects irrespective of PAP adherence [27, 28, 29]. In a long‐term open‐label study, pitolisant maintained efficacy, safety, and tolerability for up to 1 year [30]. Modafinil and armodafinil also improve subjective and objective measures of sleepiness in this population [31]. However, access to these agents varies across countries.

The therapeutic landscape of OSA is expanding beyond PAP therapy, with a recent survey indicating that patients have diverse preferences for treatment modalities, with most favouring lifestyle and oral options [32]. Promising advances in OSA treatments are helping meet this demand. Long‐term studies and refined patient selection are critical to translating these therapies into routine clinical practice and advancing personalised OSA management.

Conflicts of Interest

The authors declare no conflicts of interest.

Luu S., Lee D., and Yee B. J., “Obstructive Sleep Apnoea Treatments—Where Are We Now?,” Respirology 30, no. 10 (2025): 920–922, 10.1111/resp.70109.