Do the successes in weight loss observed with the use of glucagonoid peptide 1 (GLP-1) receptor agonists have an impact on the improvement of obstructive sleep apnea (OSA)? And will these purported benefits reduce the need for continuous positive airway pressure (CPAP) use? Experts have talked about these positives while highlighting the importance of lifestyle changes and pointing to concerns about access to GLP-1 agonists.
“I think this is a turning point in the treatment of people who are overweight or obese,” Dr. Samuel T. Kuna, MD, chief of sleep medicine at Corporal Michael J. Crescenz VA Medical Center, in the United States. “In my opinion, this exciting new era is just beginning. We finally have truly effective treatments for this population.” The study Sleep AHEAD (Action for Health in Diabetes) in 2021, led by Dr. Samuel, found that participants with OSA and type 2 diabetes who received intensive lifestyle interventions for weight loss had the severity of their OSA reduced over 10 years. The findings also showed that OSA remission at 10 years was more common with intensive lifestyle interventions than with diabetes monitoring and awareness.
Possible impact on OSA
An article published in the journal JAMA Network Open/Pulmonary Medicine reports the results of a study carried out in 2022 with 89 Spanish male adults who had moderate to severe OSA and a body mass index ≥ 25. In the research, participants used CPAP accompanied or not by intervention for weight loss and change in lifestyle. life for eight weeks. The primary outcome of the apnea-hypopnea index at six months showed that the intervention produced “clinically significant and sustained improvement in OSA”.
Dr Samuel said: “I don’t think these weight loss agents eliminate the importance of behavioral change, dietary adjustments, reducing consumption of highly processed foods and maintaining a healthy lifestyle.” He acknowledged, however, that behavioral efforts have generally been disappointing with regard to weight loss. “These medications really are a new strategy to help patients through this process,” he added.
Dr. Samuel cited a recent (2023) perspective article by Grunstein et al., published in the journal Sleep. The study shows results from phase 3 trials with GLP-1 agonists and highlights differences in weight loss compared to placebo. With subcutaneous semaglutide 2.4 mg, there were losses of 12.6% of baseline weight in patients with overweight or obesity and ≥ 1 weight-related comorbidities (except type 2 diabetes); in a similar population, the reduction was 17.8% with tirzepatide (15 mg, subcutaneous, weekly use), a combination of GLP-1 agonist and glucose-dependent insulinotropic polypeptide (GIP) agonist. The authors stated: “Provided they are available to the people who need them most—who are often socioeconomically disadvantaged—these agents could revolutionize the treatment of obesity and its many complications, including OSA.”
Grunstein et al. observed that the number of studies showing improvement in cardiometabolic outcomes (e.g., blood pressure) with OSA treatments before the emergence of incretins is “minimal.” They highlighted, however, the need to obtain more data on the risk, benefit and cost-effectiveness of treatments with incretins and cited evidence that stopping treatment leads to the resumption of weight gain and adverse cardiometabolic factors.
They also pointed out key questions that require more research to answer: what differences in response to incretins differ based on sex (women predominate in most weight loss studies, but OSA is more common in men); how CPAP users will adapt to incretins; direct comparisons of the impact on OSA with incretins versus mechanical therapy; and which target populations derive the most benefit from incretins.
Despite the unanswered questions, for Grunstein et al., the path forward is very clear: “Ultimately, the focus must shift from mechanical therapy in obesity-related OSA to weight loss, which is likely to have superior results in improving clinical outcomes, including mortality from all causes.”
Dr. Samuel agreed that one implication of this “incretin revolution” is that sleep physicians will have to expand their skills to encompass obesity management. “As the field evolves, we may need to start training our colleagues to treat these patients,” he said.
Significant impact on OSA and CPAP use
“Obesity is a risk factor for sleep apnea,” explained Dr. Saadia A. Faiz, physician and professor in the Department of Pulmonology at University of Texas MD Anderson Cancer Center, In the USA. “Therefore, with the increased use of GLP-1 agonists for weight loss, we anticipate a significant impact on both the severity of OSA and the need for CPAP.”
Referring to Dr. Samuel’s study, she said in an interview: “As stopping medication can lead to regained weight gain, an emphasis on healthy eating and exercise is crucial to controlling [da obesidade]”.
“It is important to note that there are other weight-independent factors that influence OSA, such as anatomy of the upper airways, mechanisms that modulate the stability of these pathways, sensitivity of chemoreceptors, visceral adiposity, neuroendocrine control, sleep quality and other aspects of the pathophysiology of OSA. To those who have yet to be discovered,” she said.
Cost: obstacle for some patients
“For many health plans, the coverage criteria are the diagnosis of obesity and pre-diabetes based on glycated hemoglobin. Those who do not meet the requirements have to pay out of their own pocket,” said Dr. Saadia. She mentioned a comment published in the journal Respirology, in which Dr. Garun S. Hamilton, Ph.D., and Bradley A. Edwards, Ph.D., highlighted that there are nearly 1 billion people worldwide with OSA, the majority of whom are overweight or obese. “GLP-1 agonists are so effective that they have become a worldwide phenomenon. However, the high cost of the drugs combined with the high prevalence of OSA means that there is no way for universal healthcare systems to pay for these drugs unless there are strict criteria to prioritize patients who can have subsidized access and/or there is a limit on treatment time. This will undoubtedly exacerbate inequalities in access and clinical outcomes between individuals from different socioeconomic groups, given the attributable benefit. to GLP-1 agonists will probably depend on whether you can afford them.”
Beyond health equity concerns
Evidence of clinically relevant weight loss and, consequently, reduction of other risk factors supports the widespread use of GLP-1 agonists. At the same time, however, there are warnings from advocates of treatments focused on changes in nutrition and lifestyle. They argue that prescriptions for non-pharmacological strategies that promote better sleep, healthier food choices and more physical exercise need to be more prominent and encouraged.
Regarding this, Dr. Saadia commented: “The availability and consumption of ultra-processed foods can influence food intake and weight. Specifically, in a small study of 20 adult patients admitted to the NIH Clinical Center randomized to diets with ultra-processed foods vs. unprocessed foods for 14 days, there was an increase in caloric intake and weight gain in the cohort that ate ultra-processed foods.” In the study, she cited, meals were matched in terms of calories, energy density, macronutrient content, sugar, sodium and fiber. Subjects were instructed the desired amounts. The analysis showed a weight difference of 1.8 kg between the groups in two weeks: the ultra-processed group ate 500 more calories per day and gained weight (0.9 ± 0.3 kg; P = 0.009) and body fat, while the unprocessed food group lost weight (0.9 ± 0.3 kg; P = 0.007) and body fat.
“So the type of food we choose can also have a significant impact on weight loss,” said Dr. Saadia.
Dr. Saadia A. Faiz and Dr. Samuel T. Kuna reported no conflicts of interest.
This content was translated from Medscape
