Clinical Practice Guideline Summary for Clinicians: The Role of Weight Management in the Treatment of Adult Obstructive Sleep Apnea

Summary of: Hudgel DW, Patel SR, Ahasic AM, Bartlett SJ, Bessesen DH, Coaker MA, et al.; American Thoracic Society Assembly on Sleep and Respiratory Neurobiology. The role of weight management in the treatment of adult obstructive sleep apnea: an official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2018;198:e70–e87.

Obstructive sleep apnea (OSA) is a common disorder strongly associated with excess body weight. The estimated prevalence of OSA in adults has increased substantially over the last two decades in the United States, likely owing to the rising prevalence of obesity (1). Furthermore, 41% of cases of OSA in U.S. adults (58% of moderate and severe cases) are thought to be attributable to excess weight, suggesting weight loss can have a significant role in OSA management (2).

Prior published guidelines for OSA management consistently recommend weight loss as an adjunct treatment strategy for OSA in overweight/obese patients, but they do not address the comparative effectiveness of weight loss strategies to achieve specific OSA-related outcomes. This knowledge gap may contribute to the lack of emphasis placed on weight loss by many clinicians caring for patients with OSA. To address this important aspect of OSA management, a multidisciplinary panel was convened to assess the evidence regarding the impact of various weight loss strategies on key clinical outcomes important to patients with OSA: resolution/reduction in severity of OSA; mortality; weight loss; improvement in OSA-related symptoms, including sleepiness and quality of life; impact on common OSA comorbidities, such as hypertension, diabetes, and cardiovascular disease; and burden of treatment, such as adverse effects of medications or surgery (3). The Grading of Recommendations, Assessment, Development and Evaluation approach was used to develop recommendations for the prescription of weight loss strategies for the treatment of OSA in overweight/obese adults. What follows is a summary of these guidelines for clinicians (see also Table 1).

Table 1.

Summary of recommendations

OSA Patient Population	Recommended weight loss interventions	Comparison	Strength	Comments
BMI ≥25 kg/m2	Comprehensive lifestyle intervention	No intervention	Strong
		Reduced-calorie diet with or without physical activity	Conditional
	Reduced-calorie diet with or without physical activity	No diet	Conditional
	Exercise/increased physical activity	No exercise/physical activity	Conditional
BMI ≥27 kg/m2	Antiobesity pharmacotherapy	No antiobesity pharmacotherapy	Conditional*	Without cardiovascular contraindications
BMI ≥35 kg/m2	Bariatric surgery referral	No bariatric surgery referral	Conditional*	Without surgical contraindications

Definition of abbreviation: BMI = body mass index; OSA = obstructive sleep apnea.

Comprehensive lifestyle intervention: reduced-calorie diet, physical activity, and behavioral intervention.

^*Only if unsuccessful in achieving weight loss despite comprehensive lifestyle intervention.

Comprehensive Lifestyle Interventions

• •“We recommend participation in a comprehensive lifestyle intervention program that includes a reduced-calorie diet, exercise/increased physical activity, and behavioral counseling rather than no program (strong recommendation, very low certainty in the estimated effects).”

Comprehensive lifestyle interventions are multimodal combinations of various diet, exercise, and behavior modification strategies. The seminal randomized controlled trial (RCT) of a comprehensive lifestyle intervention in mild OSA in 2009 demonstrated significant improvement in apnea–hypopnea index (AHI) and mean oxygen saturation, together with weight loss, compared with control (4). The panel reviewed nine RCTs comparing a comprehensive lifestyle intervention with no intervention in subjects with at least moderate OSA (AHI, ≥15 events/h) who were at least overweight (body mass index [BMI], ≥25 kg/m²), with most being obese (BMI, ≥30 kg/m²) or morbidly obese (BMI, ≥40 kg/m²). Dietary interventions included meal substitution and use of low- to very low–calorie targets. Comprehensive lifestyle interventions were consistently associated with a decrease in AHI and reduced daytime sleepiness; moreover, the decrease in AHI correlated with the magnitude of weight loss (4–8). Thus, the panel strongly recommended a comprehensive lifestyle intervention for overweight and obese patients with OSA.

The panel believed that including a behavioral component in a weight loss program was an important aspect to achieve results. However, behavioral interventions varied significantly across studies and included methods offered in different settings, including a dietitian-led program, a program designed for obese individuals with type 2 diabetes, support groups, and minimal contact self-monitoring protocols. Three trials explicitly included supervised or unsupervised exercise. The length of interventions in trials ranged from 9 weeks to 12 months; longer and more intense interventions had better weight loss results. Comprehensive lifestyle interventions have no demonstrable harm. Therefore, the panel was certain that the balance of desirable to undesirable consequences greatly favored a comprehensive lifestyle intervention over no intervention.

Significant weight loss was achieved in comprehensive lifestyle intervention trials for OSA that included meal substitution and in those including exercise (5, 6). Meal substitution using a nutritionally balanced but calorie-restricted bar or drink has been shown in non-OSA obesity literature to achieve greater weight loss, greater adherence, and higher likelihood of adequate nutritional intake than other diets. Meal substitution was used on a short-term basis to achieve early weight loss in some studies, and this strategy may be difficult to sustain. The panel highlighted, but did not explicitly recommend, meal substitution over other diets.

The panel specifically acknowledged having less certainty that a comprehensive lifestyle intervention (including a reduced-calorie diet) would be favored over a reduced-calorie diet alone because of limitations in available evidence. Recommendations for both diet and exercise were extrapolated from non-OSA literature (9, 10). No specific dietary composition(s) was recommended, but general recommendations were to reduce caloric intake, engage in regular aerobic activity, and make diet and exercise modifications that can be maintained in the long term. Behavioral counseling was thought to improve adherence to exercise and diet. Review of non-OSA literature suggests that multimodal strategies and higher intervention intensities predict greater weight loss.

Reduced-Calorie Diet

• •“We suggest a reduced-calorie diet (with or without exercise/increased physical activity) rather than no diet (conditional recommendation, very low certainty in the effects).”

Weight loss can be achieved by reduced-calorie diet as demonstrated consistently in randomized trials. In overweight or obese adults, meta-analyses of RCTs show that diets of 1,000–1,200 kcal/d resulted in a mean loss of about 8% of body weight compared with control diet (10). The diet composition does not appear to impact weight loss outcomes in several meta-analyses comparing fat, carbohydrate, protein content after controlling for calories consumed (11). Overall, reducing caloric intake can lead to weight loss, but long-term dietary changes are needed for durable results. Thus, a diet plan that best aligns with patients’ food preferences is likely optimal.

On the basis of available evidence from two small RCTs, the panel recommended reduced-calorie diet to achieve weight loss. Among overweight and obese subjects with OSA, these studies showed that a reduced-calorie diet alone can lead to lower sleep apnea severity. Caloric restriction compared with control diet in patients with OSA led to a greater reduction in AHI, despite no statistically significant differences in weight loss when studies were pooled (12, 13). The effects of reduced-calorie diets on other sleep parameters were not statistically significant, owing to small cohorts with high dropout rates, and follow-up durations were short.

Exercise

• •“We suggest exercise/increased physical activity rather than no exercise/increased physical activity, regardless of whether a reduced-calorie diet is added (conditional recommendation, very low certainty in the estimated effects).”

Increased physical activity in the form of aerobic exercise has been shown to have a modest effect on weight loss, possibly greater in combination with reduced-calorie diet than reduced-calorie diet alone. In a meta-analysis of trials more than 1 year in duration in subjects with obesity, exercise plus diet yielded more weight loss than diet alone (14). Increasing activity may also lead to reduced blood pressure and improved perceived health. In OSA trials, exercise programs compared with control (no specific exercise prescription) did not result in robust weight loss or significant improvements in OSA severity. However, trial methodologies varied significantly (exercise type, OSA severity, comorbidities, inclusion of positive airway pressure [PAP] therapy) (15, 16). The effect of aerobic exercise on OSA was seen in subjective outcomes (improved sleep quality, vitality, vigor) in small trials of short duration. The benefits of exercise for cardiovascular health support recommending it in obese/overweight individuals with OSA, but perhaps with modest expectations for weight loss or change in OSA severity.

A reduced-calorie diet and exercise are likely complementary for improving sleep apnea and general health. The balance of evidence supports recommending both calorie reduction and exercise rather than calorie reduction alone, but it is not yet definitive for OSA improvement.

Weight Loss Medications

• •“For patients with OSA with a BMI greater than or equal to 27 kg/m², who have not lost sufficient weight despite participating in a comprehensive lifestyle weight management program and have no contraindications or active cardiovascular disease, we suggest an evaluation for potential antiobesity pharmacotherapy (conditional recommendation, very low certainty in the estimated effects).”

Two trials randomly assigned subjects with obesity and moderate OSA to either weight loss pharmacotherapy plus a comprehensive lifestyle intervention or a comprehensive lifestyle intervention alone plus placebo (17, 18). Compared with placebo, phentermine/topiramate led to greater weight loss, a reduction in AHI, and improvement in patient-reported sleep quality (17). The SCALE (Effect of Liraglutide in Obese Subjects with Moderate or Severe Obstructive Sleep Apnea) trial found liraglutide did not provide a greater reduction in sleepiness but led to more pronounced weight loss, greater AHI reduction, and better self-reported quality of life than placebo (18). Weight loss was correlated with lower PAP in one RCT of orlistat versus placebo, but AHI and sleepiness were not assessed (19). Two other RCTs evaluating the impact of orlistat did not restrict enrollment to OSA; these trials found improvements in quality of life and vitality among patients with OSA in post hoc analyses (20, 21).

Although antiobesity medications can modestly improve OSA symptoms and severity, the risks of these medications must be carefully considered. In particular, phentermine, phentermine/topiramate, and naltrexone/bupropion may pose risks for patients with “active cardiovascular disease,” defined as “myocardial infarction or cerebrovascular accident within the past 6 months, uncontrolled hypertension, life-threatening arrhythmias, or decompensated heart failure,” although an increase in cardiovascular events was generally not observed in these trials (17). Patients with active cardiovascular disease were typically excluded from enrollment, and duration of follow-up (6–12 mo) was inadequate to fully assess risk or benefit.

Bariatric Surgery

• • “For patients with OSA with a BMI greater than or equal to 35 kg/m² whose weight has not improved despite participating in a comprehensive lifestyle intervention program for weight loss, and who have no contraindications, we suggest referral for bariatric surgery evaluation (conditional recommendation, very low certainty in the estimated effects).”

Two RCTs compared gastric banding with lifestyle modifications for obesity among patients with OSA treated with PAP and with a BMI greater than or equal to 35 kg/m². Although weight loss was greater with gastric banding in both trials, neither showed a significant benefit of gastric banding for either OSA severity by AHI or sleep symptoms (22, 23). Another trial randomized obese patients with OSA to either CPAP or gastric banding and noted similar improvements in sleep symptoms in both groups. Patients undergoing gastric banding experienced greater weight loss than individuals randomized to CPAP, but gastric banding did not improve OSA severity by AHI (24). No OSA-specific trials have evaluated bariatric procedures such as gastric bypass or sleeve gastrectomy that typically result in more weight loss than gastric banding. Although gastric banding does not appear to provide significant improvement in OSA severity, trials of a variety of bariatric surgery procedures in the general obese population provide strong evidence that bariatric surgery results in weight loss, as well as that it improves glycemic control, type 2 diabetes, and quality of life to a greater extent than nonsurgical therapies (9, 25). When one considers these non-OSA outcomes and the relative safety of bariatric surgery in the populations studied, it appears that the benefits of bariatric surgery are likely to outweigh the risks among obese individuals with OSA and a BMI greater than or equal to 35 kg/m² who have been unable to lose weight with other methods.

Conclusions

Obese and overweight patients with OSA should be counseled about specific methods to achieve and sustain weight loss. Clinicians should discuss the impact of excess weight on OSA, the benefits of weight loss, and how comprehensive lifestyle interventions can be used to accomplish this. Clinicians may offer detailed counseling, online behavioral tools, or referral to a program that offers these treatments; this is more effective than simply recommending weight loss. Clinicians may consider compiling lists of local resources and online programs to assist their patients in initiating a weight loss program. These recommendations closely parallel the National Institutes of Health/National Heart, Lung, and Blood Institute “Aim for a Healthy Weight” education campaign (26), which similarly endorses comprehensive lifestyle intervention for weight loss and weight maintenance. Recommendations based on general weight loss guidelines include reducing caloric intake by 500–1,000 kcal/d with composition tailored to patient preference, increased physical activity of at least 150 min/wk, and behavioral counseling with self-monitoring and frequent in-person sessions in the first 6 months (9). For obese patients with OSA who are unsuccessful in achieving a weight loss goal through comprehensive lifestyle programs, pharmacotherapy and weight loss surgery options should be considered, with the risks and benefits balanced by comorbidities such as diabetes and cardiovascular disease. No specific antiobesity medications or bariatric surgeries were recommended by the panel.

Weight loss does improve OSA severity, and comprehensive lifestyle interventions may help sustain benefits and improve quality of life. Obesity is a chronic disease that is a consistent contributor to OSA. A fundamental aspect of caring for obese and overweight patients with OSA should include assisting patients in the implementation of lifestyle interventions.