By Alyx Arnett
A class of weight-loss medications is gaining attention for its potential to become a pharmacological treatment option for obstructive sleep apnea (OSA) in patients with obesity.
A handful of glucagon-like peptide-1 (GLP-1) agonists have received US Food and Drug Administration (FDA) approval for obesity treatment—including liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound)—while others, like exenatide (Byetta, Bydureon), liraglutide (Victoza), semaglutide (Ozempic, Rybelsus), and tirzepatide (again, known as Mounjaro for the diabetes indication), are indicated for type 2 diabetes.
Endogenous GLP-1 has several functions, including triggering insulin release from the pancreas, as well as decreasing appetite and digestion, and this drug class mimics the GLP-1 hormone.1
While no GLP-1s have FDA marketing clearance for OSA treatment, that soon could change.
Based on results from the SURMOUNT-OSA trial, investigating tirzepatide in OSA patients with obesity, Eli Lilly submitted a supplemental new drug application to the FDA in June seeking approval for OSA. The company received FDA Fast Track designation to investigate the drug for moderate-to-severe OSA in patients with obesity in 2022.
“We are hopeful about the potential to bring a first-of-its-kind treatment option to people living with moderate-to-severe OSA and obesity, who currently have no pharmaceutical treatments for the underlying disease,” says a spokesperson for Eli Lilly.
Can GLP-1s Treat OSA?
While the connection between GLP-1s and OSA has gained more attention recently, it’s not new. A clinical trial in 2015 linked an undisclosed GLP-1 to significant improvements in OSA severity, while a 2016 clinical trial found that weight loss resulting from liraglutide was significantly associated with a reduction in the apnea-hypopnea index (AHI).4,5
These studies were among nine examined as part of a recent review investigating GLP-1s for treating OSA.6 Lead author Khang Duy Ricky Le, MD, senior lecturer in clinical medicine at Deakin School of Medicine, says, “It became a passion project to look into the research.”
Le, et al, determined evidence exists that GLP-1s may improve OSA, as defined by a reduction in the AHI. For example, a case report showed that a 24-week course of liraglutide in a 62-year-old male with HIV, obesity, type 2 diabetes, and moderate OSA managed with CPAP reduced his AHI from 27 to 7.1.7
Still, Le, who is also a general surgery registrar at Royal Melbourne Hospital, says, “I think it is too early to say this is a robust, durable, and generalizable effect given the high heterogeneity of underlying studies.” He notes a need for more rigorous randomized controlled trials with longer follow-up times to better characterize the impact of these medications on weight and OSA together, as well as gain a better understanding of effect size, optimal doses, side effects, interactions with other medications, and impacts on other comorbidities.
Evidence Builds
The SURMOUNT-OSA trial, funded by Eli Lilly, added to this evidence. Atul Malhotra, MD, a sleep medicine specialist at UC San Diego Health, and co-authors conducted two phase 3, double-blind, randomized controlled trials for tirzepatide in moderate-to-severe OSA patients with obesity who were and were not using CPAP.8
Participants not using CPAP were enrolled in trial 1 (234 participants), and those using CPAP were enrolled in trial 2 (235 participants). At baseline, the mean AHI was 51.5 in trial 1 and 49.5 in trial 2.
They were assigned 10 or 15 mg of tirzepatide or placebo for 52 weeks. Among participants, AHI decreased by an average of 25.3 events per hour in trial 1 (a 50.7% reduction) and 29.3 events per hour in trial 2 (a 58.7% reduction).
Additionally, 42.2% of patients in trial 1 and 50.2% of patients in trial 2 met the secondary endpoint of an AHI less than 5 or 5 to 14 events per hour and an Epworth Sleepiness Scale score of 10 or less—levels at which CPAP may not be recommended.
Additionally, participants saw improvements in cardiovascular risk markers, like hypoxic burden, high-sensitivity C-reactive protein concentration, and systolic blood pressure. Malhotra points out that studies have repeatedly shown CPAP fails to improve cardiovascular morbidity and mortality, “so treating the underlying cause of the sleep apnea might be required to really see the benefits.”
Malhotra says, “Everything went in the right direction. Patients felt better, and their cardiovascular risk profile improved a lot. Their body mass index improved by 18% to 20%.”
‘Nothing Short of A Miracle’ for Sleep Apnea Patients with Obesity
Katherine H. Saunders, MD, DABOM, an obesity physician at Weill Cornell Medicine, says GLP-1s “have proven to be nothing short of a miracle for patients with obesity and sleep apnea.”
Since it generally requires more weight loss to improve OSA compared to other weight-related health complications, GLP-1s are “complete game-changers” for patients with both conditions, according to Saunders. “We are now able to help more patients than ever before improve or resolve their sleep apnea,” says Saunders, who also co-founded FlyteHealth (formerly Intellihealth), a software and clinical services company democratizing access to cost-effective medical obesity treatment.
Anthony Izzo, DO, FAAN, FAASM, sleep center medical director at Community Neuroscience Services, is among a growing number of sleep medicine specialists who prescribe GLP-1s. He had a handful of patients on CPAP who were prescribed these medications for diabetes or obesity by their primary care physicians and were able to stop using CPAP. Then, the SURMOUNT-OSA trial validated clinical experience.
“With my own experience in my practice and science backing it, I felt comfortable enough to start prescribing these medications myself to my patients who aren’t able to tolerate CPAP,” Izzo says.
Raj Dasgupta, MD, FACP, FCCP, FAASM, board-certified in pulmonary, sleep, internal, and critical care medicine and chief medical advisor for Sleepopolis, isn’t prescribing GLP-1s, but he will refer OSA patients to an endocrinologist if he believes they might benefit from a GLP-1.
Dasgupta says GLP-1s have helped some of these patients by promoting weight loss, which can alleviate OSA symptoms and make it easier for them to use treatments like CPAP more consistently.
While also not prescribing GLP-1s personally, Brandon Peters, MD, FAASM, a sleep physician at Virginia Mason Medical Center, has patients taking GLP-1s for obesity or diabetes and seeing improvements in their OSA. “I have definitely had patients who, in using these medications, have lost weight and have resolved their sleep apnea, even folks with severe sleep apnea that have completely normalized their breathing with the medication,” says Peters, also a guest lecturer at Stanford University.
As the industry moves toward an indication to use these medications for OSA, Peters foresees the healthcare system he works in depending on primary care and weight loss clinic providers to initiate these medications. He says these settings are better equipped to handle the monitoring and lab work, while sleep specialists would continue to oversee patients’ CPAP adjustments and reassess their OSA as needed.
What About Other OSA Interventions?
As it’s predicted GLP-1 use will continue to rise in OSA patients, a common topic in discussions, according to Peters, is how GLP-1s might affect the use of other sleep apnea therapies, like CPAP, oral appliances, and hypoglossal nerve stimulation.9 But sleep specialists told Sleep Review they don’t believe the medications will make other therapies obsolete. Peters points out that, for one, he doesn’t believe GLP-1s can be a first-line treatment.
“It might take months or years for someone to lose a sufficient amount of weight for there to be a resolution or improvement of their sleep apnea,” he says, noting that these patients will need to be treated in another way during this time. “So it’s pretty likely that there’s not going to be a real effect on these other modalities, at least in the initial treatment phase.”
Dasgupta hopes to see GLP-1s used alongside current treatments, like CPAP. As patients lose weight, he says CPAP pressure settings might be reduced, making machine use easier and resulting in increased adherence.
According to Malhotra, “It’s always been good practice to treat both the sleep apnea and the obesity in the sense that, if somebody has excess weight, rather than just giving them a CPAP, ideally treat the body weight and the sleep apnea—not either/or.”
GLP-1 use doesn’t appear to be causing patients to simply abandon their CPAP, either. A ResMed-supported study found that, after one year, there was no significant difference in CPAP adherence or discontinuation rates among recent GLP-1 users with OSA.10
Additionally, not all OSA patients are obese and therefore wouldn’t benefit from GLP-1s. An epidemiologic study by Apnimed, a clinical-stage pharmaceutical company developing AD109, an oral drug candidate for OSA, demonstrated that most people with OSA—60.6%—are not obese.11
John Cronin, MD, senior vice president of clinical development at Apnimed, underscores the need for diverse treatment options. “In our field, for so long, we’ve had great treatments but very little choice because there just aren’t that many,” Cronin says. “I think patient choice is paramount. Precision is also paramount in terms of getting optimal treatment for people, and the appeal of different treatments might differ amongst people.”
GLP-1 Treatments Face Hurdles
While GLP-1s offer promising benefits for some patients, significant barriers remain regarding supply, cost, and insurance coverage—challenges that Saunders describes as “humongous limitations.”
Novo Nordisk’s Ozempic and Wegovy have been on the FDA’s drug shortage list since 2022. In October, Eli Lilly’s Zepbound and Mounjaro were removed from the drug shortage list after nearly two years, though the FDA warned that there still may be “intermittent localized supply disruptions.”
The removal from the list—which bars outsourcing facilities from producing compounded versions—spurred the Outsourcing Facilities Association to file a lawsuit against the FDA, saying the move will “deprive much of the public of access to a needed medicine.” In response, the FDA agreed to reevaluate the situation and will allow compounding to continue during this period.
Beyond supply issues, cost and coverage remain hurdles. A Kaiser Family Foundation (KFF) analysis found that Affordable Care Act Marketplace plans rarely cover GLP-1s approved for obesity treatment.12 According to a KFF poll, only about 1 in 4 patients using GLP-1s reported that their insurance fully covered the cost.13 More than half of adults taking these medications reported having difficulty affording them.13
For those with large employer insurance, the average out-of-pocket cost for semaglutide is around $70 per month, according to the Peterson-KFF Health System Tracker.14
Le says these challenges raise health equity questions. “Will patients from diverse backgrounds, such as those from rural or remote areas, be able to access and afford these medications? Would government subsidy be worth considering?” he says.
Malhotra adds that long-term cost-effectiveness should be evaluated, asking, “Is it worth it to put people on these medications, or are there cheaper ways of achieving that same results, which, right now, I don’t know what that would be. But there are cost considerations.”
Questions, Concerns, and Considerations
Experts stress that GLP-1s aren’t a blanket solution for weight loss. Saunders says they “should never be prescribed in the absence of a comprehensive evaluation, lifestyle management, and tons of ongoing education and support.”
Patients in the SURMOUNT-OSA clinical trial received regular lifestyle counseling sessions focused on maintaining healthy nutrition while following a 500 calorie per day deficit and at least 150 minutes of physical activity per week.
“It is perhaps too simple of an explanation to think weight is a key factor that is solely solvable by GLP-1 agonists,” says Le. “We know how complex obesity and obesogenic environments are, and efforts to address obesity should not prioritize medications but rather consider the complex holistic and systemic changes in health environments, lifestyle factors, etc, to derive more sustainable benefits.”
Careful patient selection is also critical. “GLP-1 medications are extremely powerful medications, so side effects and adverse events can occur when they’re prescribed to poorly selected patients without education, close monitoring, and support,” says Saunders.
Peters says the industry is still understanding some of the potential risks of these medications, and it will be important to identify who may be at greater risk for those issues.
Other questions also warrant further research, such as understanding why some patients with OSA don’t fully respond to GLP-1 treatments. Malhotra has submitted a grant proposal to the National Institutes of Health to explore this issue. “Is it a control of breathing problem? Is it a mechanical problem? Is it something else?” says Malhotra.
Malhotra also submitted a grant proposal to conduct a comparative effectiveness study between CPAP and tirzepatide.
“I am encouraged that there’s a new avenue for therapy, and as these medications are developed and put into practice,” says Peters. “I think we’ll be able to successfully identify who should be using them, who will be a good responder to the intervention, and who might need continued treatment.”
According to Malhotra, the bottom line is this: “Diet, exercise, and sleep are the three pillars of health. If you ignore one, the other two will suffer.”
References
- Cleveland Clinic. GLP-1 agonists. Updated 30 May 2023. Accessed 23 Oct 2024. Available at
- St-Onge MP, Tasali E. Weight loss is integral to obstructive sleep apnea management. Ten-year follow-up in Sleep AHEAD. Am J Respir Crit Care Med. 2021;203(2):161-2.
- López-Padrós C, Salord N, Alves C, et al. Effectiveness of an intensive weight-loss program for severe OSA in patients undergoing CPAP treatment: a randomized controlled trial. J Clin Sleep Med. 2020;16(4):503-14.
- Amin RS, Simakajornboon N, Szczesniak RV. Treatment of obstructive sleep apnea with glucagon like peptide-1 receptor agonist. Am J Respir Crit Care Med. 2015;191:A4144
- Blackman A, Foster GD, Zammit G, et al. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes (Lond). 2016;40(8):1310-19.
- Le KDR, Le K, Foo F. The impact of glucagon-like peptide 1 receptor agonists on obstructive sleep apnoea: a scoping review. Pharmacy (Basel). 2024;12(1):11.
- García de Lucas MD, Olalla Sierra J, Piña Fernández J. Liraglutide treatment in a patient with HIV, type 2 diabetes and sleep apnoea-hypopnoea syndrome. Diabetes Metab. 2015;41(1):102-3.
- Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 21 June 21 2024;391(13):1193-1205.
- Cole K, Woodford C, Alpert N, et al. 8-year trends in obesity, type 2 diabetes, and glucagon-like peptide-1 (GLP-1) use in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2024;209:A1084.
- Malik A, Cameron A, Woodford C, et al. 0621 Glucagon-like peptide 1 receptor agonist and positive airway pressure use in patients with OSA and obesity. Sleep. 2024;41(1):A265.
- Esmaeili N, Gell L, Taranto-Montemurro L, et al. 0866 Prevalence of obesity in obstructive sleep apnea within a large community-based cohort of middle-aged/older adults. Sleep. 2024;47(1):A372.
- KFF. Costly GLP-1 drugs are rarely covered for weight loss by Marketplace plans. 19 Oct 2023. 23 Oct 2024. Available at
- Kirzinger A, Lopes L, Muñana C, et al. KFF health tracking poll – May 2024: The public’s use and views of GLP-1 drugs. KFF. 31 May 2024. 23 Oct 2024. Available at
- Telesford I, Schwartz H, Claxton G, et al. How have costs associated with obesity changed over time? Peterson-KFF Health System Tracker. 24 March 2023. Accessed 23 Oct 2024. Available at
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