The role of weight management in sleep disordered breathing

Abstract

Sleep disordered breathing (SDB) has a significant impact on public health, with obesity being a major contributing factor. Obstructive sleep apnoea (OSA) and obesity hypoventilation syndrome (OHS) are primary conditions in SDB, strongly linked to increased body mass index. Obesity exacerbates airway narrowing, reduces lung volumes and promotes inflammation, aggravating OSA and OHS. Weight loss, achieved through nutritional therapies, pharmacotherapy or surgical therapies, reduces apnoea–hypopnea index and associated obesity-related complications. Caloric restriction and exercise provide modest improvements, often independently of substantial weight reduction. Bariatric surgery achieves substantial improvements in many cases but displays variability in outcomes. Emerging pharmacological treatments, such as glucagon-like peptide-1 receptor agonists, show promise for patients with concurrent obesity and SDB. Personalised interventions, including physiological phenotyping and multidisciplinary management, would provide effective treatment strategies. Further research into long-term outcomes, novel therapies and mechanisms beyond weight reduction is essential. Obesity prevention also remains crucial for mitigating the burden of SDB globally. This review will evaluate the role of obesity management strategies in improving SDB outcomes, and will highlight the bidirectional relationship between obesity and SDB, emphasising an integrated patient-centred approach.

Shareable abstract

This review discusses the physiological interplay between obesity and sleep disordered breathing, and explores the efficacy of various weight management strategies, including lifestyle modifications, pharmacotherapy and surgical options https://bit.ly/449uMxR

Educational aims

• To help healthcare professionals understand the physiological interplay between obesity and sleep disordered breathing.

• To explore the efficacy of various obesity management strategies, including nutritional and exercise therapies, pharmacotherapy and surgical therapies, on sleep-related breathing disorders.

• To discuss novel approaches, including emerging therapeutics and surgical techniques.

• To highlight the possible benefits of a multidisciplinary and personalised approach to managing these disorders.

Introduction

Obesity is a growing public health crisis, with prevalence rates increasing significantly over recent decades. By 2022, 23% of adults in the World Health Organization (WHO) European region had obesity, up from 16% in 2016, with further rises anticipated. Obesity-related healthcare spending in the European Union is projected to exceed 8% of national healthcare budgets over the next 30 years [1]. In the USA, obesity affected 40% of adults in 2017–2018, with annual costs reaching USD 149.4 billion during 2008–2012 [2].

Obesity affects respiratory physiology, primarily through chest wall stiffening and reduced lung compliance, driven by adiposity around the thorax and abdomen (figure 1) [3]. These changes reduce tidal volumes and impair diaphragmatic motion, leading to micro-atelectasis and heightened pulmonary blood flow [4]. Obesity causes raised intra-abdominal pressure, which affects transdiaphragmatic pressure by impairing diaphragmatic movement. This causes increased respiratory muscle workload and therefore contributes to work of breathing [5]. Airway narrowing occurs due to mechanical factors, airway hyperresponsiveness and diminished bronchodilating effects from reduced tidal action. Elevated systemic inflammatory cytokines and increased leptin levels further exacerbate bronchial inflammation and airway narrowing [3].

FIGURE 1.

Physiological effects of obesity on respiratory function.

Obesity leads to reduced expiratory reserve volume and functional residual capacity, with total lung capacity typically unaffected except in patients with severe obesity. Parameters like forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) are only mildly reduced, while diffusing capacity of the lung for carbon monoxide may increase slightly [6].

Obesity contributes significantly to respiratory disorders, notably obstructive sleep apnoea (OSA), obesity hypoventilation syndrome (OHS) and asthma. It heightens the risk of pulmonary embolism and hypertension, although its relationship with respiratory infections remains mixed. While obesity predisposes to acute respiratory distress syndrome, the “obesity paradox” suggests a potential survival advantage in certain contexts, albeit that intentional versus unintentional weight loss may explain these observations [3].

Association between obesity and sleep disordered breathing

Obstructive sleep apnoea

OSA is the most common sleep-related breathing disorder (SRBD). Its definition has varied, but efforts continue to standardise it. According to the International Classification of Sleep Disorders third edition (ICSD-3), diagnosing OSA requires either: 1) relevant symptoms/signs (e.g. sleepiness, fatigue, insomnia, snoring, observed apnoea) or an associated medical/psychiatric disorder (e.g. hypertension, coronary artery disease, heart failure), plus ≥5 predominantly obstructive events (obstructive/mixed apnoeas, hypopnoeas or respiratory-effort-related arousals) per hour of sleep; or 2) ≥15 predominantly obstructive breathing events per hour of sleep in the absence of symptoms or comorbidity [7].

These varying definitions can markedly affect prevalence estimates. Hence, it is crucial to note the diagnostic criteria when interpreting prevalence data. A frequently cited study (n=602) using an apnoea–hypopnoea index (AHI) >5 events·h⁻¹ reported OSA prevalence of 24% in men and 9% in women. If the diagnostic criteria also required the presence of excessive daytime sleepiness (EDS), known as obstructive sleep apnoea syndrome (OSAS), prevalence estimates fell to 4% and 2%, respectively [8]. Notably, the same group found that the prevalence of OSAS had increased significantly over time, to 14% and 5% for men and women, respectively, using data gathered from 2007 to 2010 [9].

OSA severity is often classified by AHI thresholds: mild (5–14 events·h⁻¹), moderate (15–29 events·h⁻¹) or severe (>30 events·h⁻¹). Originally intended for research, these cut-offs do not account for clinical symptoms (e.g. EDS), potentially leading to over- or underestimation of disease burden [7]. Pevernagie et al. [10] highlighted the limitations of relying solely on AHI: it can yield high false-positive rates, has low specificity, and shows weak correlation with symptom burden and comorbidities. Furthermore, AHI does not encompass the duration of respiratory events or characteristics of related oxygen desaturations. They recommended establishing a causal relationship, such as improvement on continuous positive airway pressure (CPAP), before attributing symptoms to OSA [10].

In summary, OSA definitions and severity thresholds should be applied with caution. An isolated AHI may be insufficient; incorporating clinical features and treatment response offers a more accurate assessment.

Pathophysiology of OSA in obesity

OSA arises from partial or complete obstruction of the upper airway during sleep. Apnoeas involve cessation of airflow for >10 s, whereas hypopnoeas indicate a ≥30% reduction in breathing amplitude for ≥10 s accompanied by a ≥3% oxygen desaturation or an arousal. This occurs when the upper airway dilator muscles fail to remain patent under the negative intrathoracic pressure generated during inspiration, especially at night, when muscle tone decreases. Forced inspiration against a closed airway generates intrathoracic pressure swings, triggering baroreceptor and chemoreceptor activation, autonomic dysfunction and frequent arousals [11, 12].

The pathophysiological basis of OSA varies between individuals. Various classification structures have been used. However, upper airway narrowing, abnormal upper airway tone and other factors can be used to broadly categorise the causes of OSA (figure 2). Patients with obesity predominantly fit into the upper airway narrowing category; however, in many cases the pathophysiology can be multifactorial [13].

FIGURE 2.

Pathophysiology of obstructive sleep apnoea (OSA). UA: upper airway.

In obesity, fat deposition in the upper airway narrows the lumen, reducing chest compliance and increasing oxygen demand, which worsens hypoxaemia. Additionally, OSA itself may raise visceral fat levels through inactivity and increased appetite, whereas CPAP can lower visceral fat even without weight loss [12]. Recurrent hypoxia and sleep disruption induce oxidative stress, producing C-reactive protein, tumour necrosis factor (TNF)-α and interleukin (IL)-6. This inflammation contributes to airway hyperresponsiveness and endothelial dysfunction, heightening cardiovascular and cerebrovascular risk [3]. Elevated leptin further narrows the airway, correlating with OSA severity [12].

Obesity hypoventilation syndrome

OHS comprises: 1) obesity (body mass index (BMI) ≥30 kg·m⁻²); 2) daytime hypercapnia (arterial carbon dioxide tension (P_aCO2) ≥45 mmHg (6 kPa)); and 3) sleep disordered breathing (SDB) after excluding other causes of alveolar hypoventilation.

OHS typically presents in more severe forms of obesity (BMI ≥40 kg·m⁻²), often with hypersomnolence, and has an estimated adult prevalence of ∼0.4%, usually in the fifth or sixth decade of life. Around 90% of OHS patients meet the AHI criteria for OSA (≥5 events·h⁻¹), most in the severe range (AHI ≥30 events·h⁻¹). Like OSA, OHS is linked to hypertension, ischaemic heart disease, heart failure and pulmonary hypertension. Diagnosis usually requires arterial blood gas sampling and polysomnography or alternatively respiratory polygraphy, but often follows a hospital admission with acute-on-chronic respiratory failure. Patients are frequently misdiagnosed with other obstructive lung diseases (e.g. COPD) [14].

Comorbidities associated with OHS and OSA may appear years before the diagnosis of a SRBD. In a Danish national study, patients typically presented with a relevant comorbidity 3 years before receiving a formal SRBD diagnosis [15]. This underscores the importance of suspecting OHS (or OSA) in individuals with obesity with associated conditions.

Pathogenesis of OHS

Three principal mechanisms drive OHS: 1) obesity-related respiratory changes (reduced chest wall compliance, increased airway resistance, intra-abdominal and transdiaphragmatic pressure changes); 2) altered respiratory drive; and 3) SDB [14].

Increased airway resistance causes premature airway closure and gas trapping (due to expiratory flow limitation), generating intrinsic positive end-expiratory pressure. This increases the respiratory workload, requiring elevated respiratory drive to maintain normal carbon dioxide levels. Over time, sustaining such an increased drive fails, leading first to nocturnal hypoventilation and eventually to daytime hypercapnia, a hallmark of OHS [14]. Central adiposity may also result in increased upper airway collapsibility through an increase in transdiaphragmatic pressure leading to a reduction in lung volumes with subsequent caudal tracheal traction [16].

In addition, blunted ventilatory responses to hypercapnia and hypoxia during sleep may arise from renal bicarbonate buffering. Leptin, a respiratory stimulant, may also become less effective due to central resistance, further contributing to hypoventilation, particularly in rapid eye movement (REM) sleep [14].

By recognising how excess weight predisposes to both airway obstruction and hypoventilation, clinicians can better diagnose and manage these intertwined conditions. Careful consideration of clinical features, comorbidities and the limitations of AHI-based thresholds is vital in tailoring effective treatment strategies for OSA and OHS.

Obesity management strategies

Weight gain strongly correlates with the development of SRBDs. Conversely, weight loss is an established therapeutic strategy. A recent meta-analysis of 32 studies found that reducing BMI by 10%, 20% or 30% decreased the AHI by approximately 36%, 57% and 69%, respectively [17]. The relationship was non-linear, with each incremental decrease in BMI yielding smaller additional AHI reductions. This effect was consistent across weight-loss interventions (diet, exercise, medication and bariatric surgery) and was sustained for 1–3 years, even with partial weight regain [18]. Notably, some lifestyle interventions (e.g. diet and exercise) offer benefits beyond weight loss alone.

Diet and exercise

The American Academy of Sleep Medicine (AASM) recommends lifestyle interventions (dietary change and exercise) as behavioural treatments for SRBDs [18].

Dietary interventions

Caloric restriction

Calorie-restricted diets (1000–1200 kcal·day⁻¹) consistently produce weight loss, averaging 8% over 6 months [19]. However, regain of weight is common due to the non-physiological nature of the intervention. Two randomised trials in patients with OSA showed statistically significant reductions in AHI and oxygen desaturation with caloric restriction. One trial (n=23) reported a 9% weight reduction and decreases in AHI in both REM sleep (57.0±3.2 to 37.6±5.7 events·h⁻¹; p<0.01) and non-REM sleep (55.0±7.5 to 29.2±7.1 events·h⁻¹; p<0.01) at 5–8 months follow-up [20]. Another study (n=29) using a regimen of <800 kcal·day⁻¹ demonstrated modest but statistically significant decreases in AHI and improvement in minimum oxygen saturation level after 4 months [21]. Neither study found changes in daytime sleepiness or quality of life.

Dietary composition

Most studies show nutritional therapies can achieve >10% weight loss in 15–20% of patients [22]. These approaches normally emphasise low-fat, calorie-restricted diets, but dietary composition (e.g. low-carbohydrate or Mediterranean) may independently influence SRBDs. Low-carbohydrate diets, which reduce abdominal fat and systemic inflammation, are more effective for weight loss than low-fat diets, although formal SRBD data are limited. A case report documented a marked AHI decrease (from 71.2 to 2.8 events·h⁻¹) over 18 months in a Japanese male patient on a very-low-carbohydrate diet, although longer-term data were not available [23].

Mediterranean diets may also benefit SRBDs beyond weight reduction [18]. In one study (n=40), those on a Mediterranean diet had greater REM sleep AHI reduction than those on a prudent diet (both calorie restricted), with better adherence but no overall AHI difference [24]. Proposed mechanisms include reduced central adiposity and anti-inflammatory effects that could improve upper airway neuromuscular control.

Overall, while nutritional therapies such as low-carbohydrate and Mediterranean diets appear promising, these warrant further research. Response to nutritional therapies can usually be predicted within 3 months and if a patient does not respond then their treatment should be changed or escalated [22].

Exercise therapies

Population studies indicate that physically active individuals have a lower risk of developing a SRBD, independent of body habitus [25]. Trials show that moderate-intensity aerobic or combined aerobic/resistance training can decrease AHI, often without major weight changes. One randomised controlled trial (RCT) (n=43) found 150 min per week of moderate-intensity aerobic exercise plus twice-weekly resistance training reduced AHI (from 32.2±5.6 to 24.6±4.4 events·h⁻¹; p<0.01) over 12 weeks [25]. Other studies observed similar modest reductions in AHI and oxygen desaturation index (ODI) [26]. However, exercise as an adjunct to CPAP therapy has not consistently lowered AHI beyond CPAP alone [27].

A meta-analysis of 12 studies (n=526) concluded that exercise reduced AHI by 7 events·h⁻¹ and improved daytime sleepiness [27]. Variations in design make comparisons difficult, but exercise probably exerts both weight-dependent and weight-independent benefits. Further research is needed to determine the optimal exercise regimen for SRBD management. Response to exercise therapies can usually be predicted within 3 months and if a patient does not respond then their treatment should be changed or escalated.

Combined diet and exercise therapies

A meta-analysis of RCTs compared the effect on weight loss of diet or exercise alone versus combined diet and exercise therapy. 20% greater initial weight loss was seen in those who combined diet and exercise therapy versus diet or exercise alone. Furthermore, weight loss was more likely to be sustained [28]. However, a recent meta-analysis (n=702) looking at the impact of the same interventions on OSA parameters found that combined diet and exercise did not cause a greater reduction in AHI than diet or exercise therapy alone. A number of limitations of this meta-analysis were raised, however, including variable inclusion of CPAP therapy, a relative lack of combined (diet and exercise) intervention subjects and limited intention-to-treat data [29]. Ultimately, more study in this area will be needed to determine whether there is an incremental benefit of combining these measures.

Mechanism of exercise in SRBDs

Exercise appears to improve SRBDs through several mechanisms. One hypothesis is that reducing leg fluid volume lowers nocturnal rostral fluid shift, thereby decreasing tissue pressure around the upper airway and therefore its collapsibility. In a study of patients with sleep apnoea and coronary artery disease (n=44), subjects participated in 30 min of moderate-intensity walking five times weekly over 4 weeks. The study found significant decreases in AHI, overnight leg fluid shift and morning neck circumference, and an increase in upper airway cross-sectional area, despite no change in cardiorespiratory fitness or body weight [30]. A similar effect was previously observed in patients with end-stage kidney disease with OSA undergoing dialysis. AHI reduced by 36% (43.8±20.3 to 28.0±17.7 events·h⁻¹; p<0.001) following ultrafiltration of 2.17 L [31].

Exercise may also reduce visceral fat despite minimal overall weight loss, thus diminishing the load on the diaphragm and enhancing rib cage expansion [32]. This effect probably reflects increased catecholamine release, which preferentially stimulates lipolysis in visceral over subcutaneous fat. Similarly, reductions in adipose tissue around the upper airway and tongue may improve airway patency [33].

Finally, exercise-induced hormonal adaptations parallel those seen with dietary modifications. Exercise lowers serum leptin levels and improves its sensitivity. It also increases growth hormone secretion, which decreases abdominal fat and has potent anti-inflammatory properties. These changes may diminish airway hyperresponsiveness and augment upper airway control, thereby improving SRBDs [33]. Collectively, these adaptations can mitigate multiple contributing factors to SRBD severity.

Bariatric surgery

Bariatric surgery is known to improve OSA substantially, with some patients even achieving remission [34]. 77% of patients who undergo bariatric surgery have OSA. SRBDs increase the peri-operative risk. Therefore, polysomnography is recommended as part of the pre-operative assessment and is a common point of diagnosis [12]. In many cases, treatment will be initiated several months prior to surgery to reduce this risk. However, this has the potential to result in delays to surgery. This is particularly the case when access to polysomnography is limited due to associated costs, resources or lack of availability. Therefore, more readily available options like type 3 (cardiopulmonary) and type 4 (oximetry) studies should be considered in settings where there is limited access to more comprehensive sleep studies [35].

Indications for bariatric surgery

Bariatric surgery is typically considered following failure of weight loss with diet and exercise strategies. Indications for bariatric surgery encompass BMI and associated obesity-related complications and include: 1) BMI of ≥40 kg·m⁻²; 2) BMI of 35–39.9 kg·m⁻² and an obesity-related complication (such as metabolic dysfunction-associated steatotic liver disease (MASLD), gastro-oesophageal reflux disease (GORD), asthma, venous stasis disease, severe urinary incontinence and debilitating osteoarthritis); and 3) BMI of 30–34.9 kg·m⁻² and type 2 diabetes. There is less evidence demonstrating the benefit of surgery for those with a BMI of 30–34.9 kg·m⁻² with other complications. There are no absolute contraindications for bariatric surgery; however, relative contraindications include severe heart failure, unstable coronary artery disease, end-stage lung disease, actively treated cancer and drug or alcohol dependency [36].

Types of bariatric surgery

A sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB), which are typically performed laparoscopically, are the two most common bariatric surgeries. Biliopancreatic diversion with duodenal switch (BPD/DS) is performed in some centres. Gastric banding, previously a common surgery, is not widely performed any more, due to significant associated complications [37]. However, it is still performed in some centres as a low-cost alternative.

Efficacy in OSA

A recent meta-analysis of 32 studies (n=2310) found that bariatric surgery led to OSA remission (i.e. no longer needing CPAP) in 65% of patients, accompanied by significant reductions in AHI (of 19.3±4.6 events·h⁻¹) and BMI (of 11.9±1.5 kg·m⁻²) [38]. Another meta-analysis of 24 studies (n=1043) demonstrated improvements not only in AHI but also in other measures, such as FVC, Epworth Sleepiness Scale (ESS) scores, mean or nadir peripheral oxygen saturation (S_pO2), ODI, time spent at S_pO2 <90%, arousal index and neck and waist circumferences. These benefits were more pronounced in patients with severe obesity [39]. A large longitudinal study evaluating which surgical approach is most beneficial for a given patient found that RYGB or BPD/DS was more likely to induce OSA remission than sleeve gastrectomy, noting that individuals with a higher number of obesity-related complications are also more inclined to undergo RYGB or BPD/DS rather than sleeve gastrectomy [40].

Despite these encouraging results, further analysis reveals substantial variability in individual responses to surgery. Some studies suggest that moderate weight loss provides similar improvements in OSA parameters, implying that the profound weight reduction often seen with bariatric procedures may not confer additional benefit [41]. Notably, improvements have been observed soon after surgery, even before significant weight loss targets are met [42].

In some patients, bariatric surgery-induced weight loss does not cause as significant a reduction in OSA parameters. This indicates that other factors may contribute to outcomes, such as pre-operative OSA severity, the degree of post-operative weight reduction and premorbid type 2 diabetes. Ethnicity, pathophysiological variables and anatomical features also play a role; for example, an atypical upper airway (lowered hyoid bone, thicker soft palate) can limit pharyngeal space. Individual patterns of fat distribution may exert additional effects.

Study heterogeneity and varying definitions of OSA and remission further complicate outcome comparisons. While some studies define remission as AHI <5 events·h⁻¹, others use AHI <15 events·h⁻¹ or “no longer requiring CPAP/bilevel positive airway pressure”. Moreover, relying on respiratory polygraphy in lieu of full polysomnography may miss up to 30% of AHI events [34]. Polysomnography is not a perfect test either, with studies demonstrating significant night-to-night variability in AHI [43]. In fact, many studies demonstrate that AHI <15 events·h⁻¹ is not achieved despite substantial weight loss with bariatric surgery [44].

The mechanisms underpinning OSA improvement after bariatric surgery primarily involve enhanced upper airway patency associated with weight loss. Similar to the effects of diet and exercise, reduced visceral adiposity leads to better ventilation and oxygenation, accompanied by lower levels of pro-inflammatory cytokines such as TNF-α and IL-6, which otherwise contribute to airway narrowing [42].

Efficacy in OSA and OHS

Evidence specific to bariatric surgery in OHS is limited. However, an early observational study (n=29) reported remission of OHS in 86.2% of participants undergoing RYGB, along with marked improvements in gas exchange (arterial oxygen tension increase of 15 mmHg (2 kPa) and P_aCO2 reduction of 10 mmHg (1.3 kPa)) and subjective improvements in daytime hypersomnolence [45]. Achieving and maintaining substantial weight loss (25–30% of total body weight) appears necessary in order to have a meaningful impact on hypoventilation in OHS, and such a degree of weight reduction generally necessitates surgical intervention.

In summary, bariatric surgery has a clear role in the treatment of SRBDs, with high rates of remission. Surgery may provide definitive therapy, particularly for those with a higher BMI. However, interindividual variability does exist, probably due to individual factors. Furthermore, some research suggests that the extremes of weight loss seen in bariatric surgery do not provide additional benefit in SRBDs beyond mild–moderate weight loss. Finally, many patients do not achieve AHI <15 events·h⁻¹ post-operatively. Despite this, many will discontinue their CPAP, which contributes to weight regain. One study (n=22) found that CPAP adherence in those who underwent bariatric surgery declined from 83.3% pre-operatively to 38.1% at 1 year after surgery. BMI was found to increase in those not using CPAP at long-term follow-up (mean 7.2 years) versus those who continued CPAP (increase of 6.8 versus decrease of 1.8 kg·m⁻²; p=0.05) [46].

Pharmacotherapy

Medications targeting the disease of obesity and its related complications are becoming more effective. Their efficacy in treating SRBDs is also becoming apparent from clinical trial data. This section presents an overview of weight loss medications.

Orlistat

Mechanism of action

Orlistat acts by inhibiting gastrointestinal lipase, thereby reducing fat absorption. When taken with food, it prevents the hydrolysis of triglycerides, preventing the absorption of monoacylglycerides and free fatty acids and contributing to weight loss.

Clinical efficacy and side-effects

Orlistat was one of the first of a wave of anti-obesity drugs, originally gaining US Food and Drug Administration (FDA) market approval in 1999. Its efficacy is modest, with an average of 5–10% weight loss. The effects of orlistat on SRBDs have not been studied. Gastrointestinal side-effects include steatorrhoea, abdominal pain and flatus with oily discharge, which commonly occur when the patient eats too much fat [47].

Glucagon-like peptide-1 receptor agonists

Mechanism of action

Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from the L-cells in the intestines. It is released in response to macronutrient intake, particularly carbohydrates. GLP-1 binds to its receptors on pancreatic β-cells, stimulating insulin secretion and inhibiting glucagon release. It binds to receptors in the pylorus, thereby slowing gastric emptying. It also binds to appetite-regulating centres in the subcortical areas of the brain, causing satiation. As GLP-1 has a very short half-life of 2–3 min, GLP-1 receptor agonists (e.g. liraglutide, semaglutide and tirzepatide) function by resisting degradation and enhancing these physiological effects [48]. Tirzepatide acts as a dual GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist; GIP is a hormone that also stimulates insulin secretion. In a recently published head-to-head study, compared to semaglutide, the dual agonism of tirzepatide provided a greater reduction in body weight and waist circumference over 72 weeks [49].

Clinical efficacy and side-effects

Liraglutide

A randomised trial studied those with obesity and moderate–severe OSA (n=276) who were unwilling or unable to use CPAP therapy. The treatment cohort received 3 mg of liraglutide for 32 weeks while the control cohort received a placebo. Both cohorts received counselling about diet (500 kcal·day⁻¹ deficit) and exercise (>150 min physical activity weekly). The mean reduction in AHI was greater with liraglutide than placebo (12.2±1.8 versus 6.1±2.0 events·h⁻¹; p<0.05). Weight loss of 5.7% was observed with liraglutide versus 1.6% in the control group. A post hoc analysis demonstrated a correlation between degree of weight loss and OSA end-points (p<0.01). Interestingly, most of the reduction in mean AHI occurred by week 12, despite continued weight loss beyond this point. No statistically significant change was seen in ODI, total sleep time, wakefulness after sleep onset, ESS score and desaturation mean or nadir. The modest improvements seen with liraglutide, particularly in those with severe OSA, result in the clinical significance of its use being unclear. The effect may be more significant in those with mild–moderate disease or as an adjunct to CPAP therapy. Side-effects were predominantly gastrointestinal in nature, including nausea, vomiting, diarrhoea and dyspepsia. Importantly, these side-effects were generally mild or moderate and abated after 8 weeks [50].

Semaglutide

Surprisingly, no RCT has reported the use of semaglutide in SRBDs thus far. However, the effect on weight following withdrawal of semaglutide has been studied. Participants were found to regain two-thirds of their prior weight loss, 1 year following discontinuation. Similar changes were seen in cardiometabolic variables. This reinforces the need for continuation of treatment in order to maintain weight loss and associated improvements in sleep parameters [51].

Tirzepatide

A recently published RCT studied the effect of the novel combined GLP-1 and GIP receptor agonist tirzepatide in patients with moderate–severe OSA with obesity both on and off CPAP [52]. The treatment cohort received 10–15 mg of tirzepatide and the control cohort received a placebo. Similar to the liraglutide trial, lifestyle counselling for diet and exercise was given. The change in AHI for those not on CPAP was −25.3±4.0 and −5.3±4.1 events·h⁻¹ in the treatment and control cohorts, respectively, at 52 weeks (p<0.001). Reductions in AHI of −29.3±3.9 and −5.5±4.4 events·h⁻¹ were seen in the treatment and control arms, respectively, in those on CPAP (p<0.001). This was associated with weight loss of 17.7% and 19.6% at 52 weeks in the non-CPAP and CPAP cohorts, respectively, with minimal weight loss being observed in the control groups. Significant improvements in secondary end-points including hypoxic burden, blood pressure and PROMIS (Patient-Reported Outcomes Measurement Information System) sleep-related score were also seen. One of the end-points was an AHI of <5 events·h⁻¹ or AHI of 5–14 events·h⁻¹ with ESS score ≤10. In the non-CPAP group, 48% of those on tirzepatide versus 19% in the control group met this end-point. In the CPAP group, 60% on the treatment versus 16% in the control group met this end-point. Similar to other GLP-1 receptor agonists, the most commonly reported side-effects were gastrointestinal in nature and they were generally mild to moderate in severity [52]. Tirzepatide has recently been approved by the FDA as the first drug for the treatment of moderate–severe OSA.

In summary, while the effect of liraglutide on SRBDs is limited, tirzepatide offers more promising data. As there are many similar new medications in the pipeline (see the section “New therapeutics”), anti-obesity drugs are likely to have a significant role in the long-term management of SRBDs in the future.

Clinical implications and recommendations

Integrated approach

SRBDs are associated with many comorbidities. They also affect cognitive, social and occupational performance. The wide-ranging nature of SRBDs stresses the importance of managing patients as a whole, rather than a condition in isolation. In order to do this and successfully implement the strategies discussed in this review, ideally this would be under the guidance of a multidisciplinary team, provided enough resources are available and access to a multidisciplinary team does not become a barrier to care. A multidisciplinary team should consist of physicians, bariatric surgeons, dietitians, advanced nurse practitioners, nurses, pharmacists, physiotherapists, occupational therapists and social workers, although a primary care physician or respiratory medicine specialist can initiate treatment. Disease management programmes have been effective in the treatment of other chronic conditions with associated morbidities and costs, like heart failure and diabetes [53]. Similarly, SRBDs are likely to benefit from such an integrated approach, provided it does not become a barrier to care.

Personalised medicine

Patients with SRBDs are a heterogeneous group with varying response to therapy. Historically, CPAP has been the mainstay of treatment with a “one size fits all” approach. Long-term compliance with CPAP therapy is often poor and its efficacy is variable, with 25–30% of those using CPAP having a residual AHI of >10 events·h⁻¹. Lack of symptomatic relief and discomfort for many often results in non-adherence [54]. Identification of specific anatomical and physiological factors, like those discussed in this article, may aid in determining a treatment approach that is both effective and tolerable for a specific patient. The PALM (passive critical closing pressure, arousal threshold, loop gain and muscle responsiveness) scale has been developed to stratify OSA patients on the basis of physiological phenotypes, to identify responsiveness to CPAP, mandibular advancement devices and lifestyle measures [55]. In the same way, it may be possible to use a scoring system that would determine phenotypically the weight loss measures that would be most suited to a certain patient.

Long-term follow-up

In many of the weight management strategies discussed, the impact of the intervention can be seen in a relatively short period of time, often within 3–6 months. With some interventions, there is little additional benefit beyond this interval. Therefore, short-interval follow-up appointments would permit assessment of the effect of an intervention. They also provide an opportunity to augment or discontinue a treatment strategy and consider an alternative. For a chronic disease, regular follow-up appointments are important for continued assessment of response and alteration to the chosen therapy.

Future directions

New therapeutics

A number of novel weight loss therapeutics are in development (table 1). Similar to tirzepatide, many of these medications act as receptor agonists for combinations of GLP-1 with other entero-pancreatic hormones that have synergistic properties. These include CagriSema (GLP-1/amylin), survodutide (GLP-1/glucagon) and retatrutide (GLP-1/GIP/glucagon), which are currently in phase 3 of their development. Other medications include bimagrumab, a monoclonal antibody therapy that stimulates skeletal muscle growth by inhibiting the activin type II receptor, which reduces fat mass and increases lean mass. Similar to tirzepatide, these medications may confer additional benefit in the treatment of obesity and SRBDs.

TABLE 1.

Therapeutics in development (phase 2 and 3) for the treatment of obesity

Name	Dose	Administration	Mechanism	Manufacturer	Completion date
Phase 3 trials
Semaglutide	50 mg	p.o., daily	GLP-1 RA	Novo Nordisk	Completed
Orforglipron	NA	p.o., daily	GLP-1 RA	Eli Lilly	July 2027
Semaglutide	7.2 mg	s.c., weekly	GLP-1 RA	Novo Nordisk	Completed
Tirzepatide	5–15 mg	s.c., weekly	GLP-1 RA + GIP RA	Eli Lilly	Completed
CagriSema	2.4 mg + 2.4 mg	s.c., weekly	GLP-1 RA + amylin RA	Novo Nordisk	October 2026
Survodutide	3.6–6 mg	s.c., weekly	GLP-1 RA + GCG RA	Boehringer Ingelheim	Completed
Mazdutide	4–6 mg	s.c., weekly	GLP-1 RA + GCG RA	Innovent Biologics	Completed
Mazdutide	9 mg	s.c., weekly	GLP-1 RA + GCG RA	Innovent Biologics	September 2025
Retatrutide	4–12 mg	s.c., weekly	GLP-1 RA + GIP RA + GCG RA	Eli Lilly	May 2026
Phase 2 trials
Danuglipron	40–200 mg	p.o., twice daily	GLP-1 RA	Pfizer	Completed
Cagrilintide	0.3–4.5 mg	s.c., weekly	Amylin RA	Novo Nordisk	Completed
PYY 1875	0.03–2.4 mg	s.c., NA	PYY RA	Novo Nordisk	Completed
Efinopegdutide	5–10 mg	s.c., weekly	GLP-1 RA + GCG RA	Hanmi Pharmaceutical	Completed
Pemvidutide	1.2–2.4 mg	s.c., weekly	GLP-1 RA + GCG RA	Altimmune	Completed
AMG 133	NA	s.c., monthly	GLP-1 RA + GIP receptor antagonist	Amgen	January 2026
NNC0165-1875 +  semaglutide	1–2 mg + 2.4 mg	s.c., every 2–4 weeks	GLP-1 RA + PYY RA	Novo Nordisk	Completed
Dapiglutide	4–6 mg	s.c., weekly	GLP-1 RA + GLP-2 RA	Zealand Pharma	August 2025
Bimagrumab +  semaglutide	30 mg·kg−1 + 1–2.4 mg	i.v., monthly (bimagrumab); s.c., weekly (semaglutide)	Activin receptor II inhibition + GLP-1 RA	Versanis Bio	June 2025
S-309309	NA	p.o., daily	MGAT2	Shionogi	Completed

GLP: glucagon-like peptide; RA: receptor agonist; GIP: glucose-dependent insulinotropic polypeptide; GCG: glucagon; PYY: peptide YY; MGAT2: monoacylglyceroltransferase 2; p.o.: oral; s.c.: subcutaneous; i.v.: intravenous; NA: not available.

Technological innovations

Novel surgical techniques are becoming increasingly popular. These include intragastric balloons (figure 3), such as the Heliosphere balloon and Spatz3. These devices are inserted into the stomach endoscopically and generally remain in situ for 6–8 months before removal. Studies have demonstrated reasonable weight loss of 10–15%, although this does not persist after removal. The devices reduce appetite and calorie intake by delaying gastric emptying and influencing satiety hormones. The balloons are often used as temporary measures due to long waiting lists for bariatric surgery and as a “bridging treatment” for severe obesity to lower peri-operative risks of major surgery [37].

FIGURE 3.

Intragastric balloon demonstrating balloon following inflation within the stomach.

Endoscopic sleeve gastrectomy uses endoscopy instead of surgery to tabularise and reshape the stomach. It is associated with fewer complications, faster recovery time and shorter hospital admissions. Further study of these devices is required to determine their long-term safety and efficacy profiles [37].

A number of other endoscopic techniques are currently in development. These include linear magnetic compression anastomosis. This uses magnets to create a suture-less and staple-free anastomosis. The magnets compress and fuse the tissue over time, forming a stable anastomosis, following which the magnets are expelled from the body naturally [56]. The EndoQuest is another exciting platform that is currently in development. It provides an endoscopic robotic platform with the capabilities of providing scar-free flexible endoluminal robotic surgery. It avoids the need for laparoscopy or open surgery and the associated damage to healthy tissue [57].

Public health initiatives

The AASM commissioned a market research programme entitled “Hidden health crisis costing America billions”. The programme estimated that the costs of undiagnosed and untreated OSA to employers and patients amounted to USD 149.6 billion in 2015. This was predominantly due to lost productivity and absenteeism but also to associated obesity-related complications and road traffic and workplace accidents [58].

Due to the relatively low cost of implementing some of the aforementioned weight loss measures, there is a strong argument for public health campaigns promoting comprehensive diagnosis and long-term management of OSA. This is in line with the WHO recommendation of prevention of non-communicable disease by reducing common risk factors such as tobacco use, harmful alcohol use, physical inactivity and eating unhealthy diets. It is likely that even small changes would have a significant impact in terms of cost–benefit analysis. Furthermore, the economic interest currently largely focuses on diagnosis and treatment of SRBDs. As is often the case, the most beneficial public health measure would be aimed at preventing obesity and associated comorbidities like SRBDs.

Conclusion

Weight loss, regardless of the strategy, via nutritional, exercise, pharmacological or surgical therapies, has an impact on SRBDs. Poor adherence and response to CPAP therapy, the mainstay of treatment for SRBDs, emphasise the need for alternative treatments. These include the various weight loss strategies discussed in this review, either as monotherapy or as an adjunct to CPAP. While some of these strategies, like bariatric surgery and pharmacotherapy, result in significant weight loss, some have more modest effects. The impact of such modest weight loss on SRBDs is not clearly established as there is significant variation in the literature as to what constitutes clinically significant weight loss. According to the American Association of Clinical Endocrinologists, clinically significant improvement in OSA requires at least 7–11% weight loss and the weight loss required is likely to be higher in OHS [59]. However, as outlined, certain weight loss strategies, including diet, exercise and surgery, have beneficial effects on SRBDs that are independent of weight loss. As a result, such measures should not only be viewed as a means of weight loss but as part of a holistic approach to managing SRBDs. Ultimately, further research is required to determine the true benefit of such measures for SRBDs, due to the variability of outcomes reported in the literature. Nonetheless, the current consensus favours the use of diet and exercise as a management strategy in SRBDs.

A number of novel pharmacological and surgical approaches are currently in the pipeline, with favourable efficacy data, and there has been significant advancement in existing surgical techniques. In light of this, these strategies have significant potential in the management of SRBDs and their use is likely to become more widespread in the future.

Key points

• Weight loss strategies, including nutritional, exercise and surgical therapies, can have beneficial effects on SRBDs that are independent of weight loss.

• Pharmacotherapies are simple and safe strategies that are scalable for the treatment of SRBDs.

• Comorbidities associated with OHS and OSA may appear years before the diagnosis of a SRBD and clinicians should remain vigilant of this.

• Bariatric surgery can have significant effects on SRBD parameters. However, inter-individual variability exists due to underlying factors. Furthermore, many patients do not achieve remission of OSA despite significant weight loss.

• CPAP remains the mainstay for treatment of SRBDs. However, significant issues exist with respect to adherence, making novel therapeutics and surgical techniques exciting alternatives.

Self-evaluation questions

1. What AHI is consistent with a diagnosis of moderate OSA?

   1. <5 events·h⁻¹
   2. 5–14 events·h⁻¹
   3. 15–29 events·h⁻¹
   4. >30 events·h⁻¹

2. In addition to obesity (BMI ≥30 kg·m⁻²) and SDB, which additional parameter is required for a diagnosis of OHS?

3. Is the following statement true or false? OSA has a significant impact on FVC and FEV₁.

4. Which of these is not an indication for bariatric surgery?

   1. BMI ≥40 kg·m⁻²
   2. BMI 35–39.9 kg·m⁻² and an obesity-related complication (such as MASLD, GORD, asthma, venous stasis disease, severe urinary incontinence and debilitating osteoarthritis)
   3. BMI 30–34.9 kg·m⁻² and an obesity-related complication (such as MASLD, GORD, asthma, venous stasis disease, severe urinary incontinence and debilitating osteoarthritis)
   4. BMI 30–34.9 kg·m⁻² and type 2 diabetes

5. In addition to being a GLP-1 receptor agonist, what additional mechanism of action does tirzepatide have?

Suggested answers

1. c.

2. Daytime hypercapnia (P_aCO2 ≥45 mmHg (6 kPa)).

3. False.

4. c.

5. GIP receptor agonist.