In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide and tirzepatide have made headlines for their impressive ability to promote weight loss and improve glycemic control among people with type 2 diabetes. But with the recent FDA approval of Zepbound® (tirzepatide) to treat obstructive sleep apnea (OSA), these medications are stepping into a new spotlight — one that highlights their emerging role in ways that go beyond shedding pounds.
This development, experts say, marks a turning point in sleep medicine.
“Sleep apnea is now entering an era where medications, not just devices like continuous positive airway pressure (CPAP), can play a role in treatment,” says Atul Malhotra, MD, a leading sleep researcher at University of California at San Diego Health. “And it’s not just about losing weight. There are metabolic, inflammatory, and even potential neurological effects that GLP-1s may be addressing, all of which contribute to better sleep.”
For many patients, weight loss is the most important step in managing sleep apnea. “The number one modifiable risk factor for sleep apnea is obesity,” saysAlcibiades Rodriguez, MD, medical director of the Comprehensive Epilepsy Center — Sleep Center at NYU Langone. “When patients lose weight — whether it’s through traditional means, bariatric surgery, or now with GLP-1 receptor agonists — we often see their sleep apnea improve or even resolve completely.”
At first, Dr Rodriguez saw these improvements among patients who were prescribed GLP-1 receptor agonists for diabetes or weight loss and happened to also be under his care for sleep apnea. Now, with the medication approved specifically for OSA, he is using it regularly as part of his treatment strategy.
“I’m prescribing GLP-1 medications regularly now, and the results so far have been encouraging,” he says. “We’ve had patients who went from needing CPAP machines every night to barely needing them at all after significant weight loss. Some can stop using them altogether.”
Indeed, while the weight loss benefits of GLP-1 receptor agonists remain central to their effectiveness against sleep apnea, researchers are increasingly finding that their positive impact on sleep may run deeper. For general practitioners and non-specialists managing patients with metabolic disorders, obesity, or sleep issues, the implications of these medications could be wide-ranging.
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GLP-1s are a game-changer, but they’re not magic. Patients need to understand that GLP-1s work best as part of a comprehensive plan.
Alcibiades Rodriguez, MD
A Groundbreaking Approval
In late 2024, the FDA’s approval of Zepbound for the treatment of OSA marks the first time a GLP-1 receptor agonist has been cleared for use outside of weight management and diabetes treatment. It is also the first-ever FDA-approved medication specifically for OSA, a condition that — until now — has primarily relied on mechanical interventions such as CPAP machines and oral appliances.
“Until now, our options have focused on devices or surgical interventions,” says Dr Malhotra, an internationally recognized expert in sleep apnea who is the recipient of the 2024 Sleep and Respiratory Neurobiology Lifetime Achievement Award by the American Thoracic Society. “Having a medication approved for OSA opens a whole new avenue for treatment.”
The approval followed the success of the SURMOUNT-OSA trial, a pivotal study designed to evaluate the impact of tirzepatide on sleep apnea. Led byDr Malhotra, the trial found that patients with obesity experienced significant improvements in their sleep apnea severity — some moving from severe to mild OSA or resolution of the condition altogether.1
“We were already seeing patients taking these medications for diabetes or weight loss report better sleep, but the trial showed us it’s more than just shedding pounds,” he says. “We saw reductions in inflammation, improvements in breathing and other benefits that go beyond weight loss alone.”
The approval represents a shift in how sleep apnea will be treated moving forward, Dr Rodriguez says.
“Patients were calling within days of the announcement,” he says. “CPAP can be a challenge, and many are eager for alternatives. Now we have an FDA-approved medication that not only helps manage sleep apnea but also improves metabolic health and reduces cardiovascular risks.”
And this approval may be just the start. Researchers are already investigating GLP-1 receptor agonists for other conditions beyond OSA, including neurodegenerative diseases, anxiety, and cardiovascular health.
“We’re still learning, but it’s clear these medications are opening new possibilities for how we approach complex conditions beyond sleep apnea,” Rodriguez says.
The Weight-Sleep Connection
OSA happens when the airway becomes blocked during sleep, causing frequent pauses in breathing. It is often marked by loud snoring, gasping for air, and daytime fatigue. The condition affects an estimated 2% to 4% of the population.2 Although it can develop in anyone, OSA is more common among people with overweight or obesity and tends to worsen with age. Fat deposits around the neck and upper airway can narrow the airway, making weight loss a key strategy in managing the condition.
Tirzepatide helps by targeting receptors for 2 gut hormones — GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). These hormones reduce appetite and food intake, leading to significant weight loss. Studies have shown that this weight loss improves OSA symptoms.1
The results that led to Zepbound’s approval for sleep apnea came from 2 randomized, double-blind, placebo-controlled studies involving 469 adults without type 2 diabetes. One study included participants who were using positive airway pressure (PAP), the current standard of care for OSA, while the other enrolled participants who were unable or unwilling to use PAP.1
In both studies, participants were randomly assigned to receive either 10 or 15 mg of tirzepatide or a placebo once weekly for 52 weeks. The main measure of success was the change in the apnea-hypopnea index (AHI), which tracks how many times per hour a person either stops breathing (apnea) or breathes shallowly (hypopnea) during sleep.1
After a year of treatment, participants receiving tirzepatide vs placebo showed statistically significant reductions in AHI. Many saw their sleep apnea improve to mild or even remission, along with relief from symptoms such as daytime fatigue. On average, participants lost 18% to 20% of their body weight, a key factor in reducing airway obstruction.2
The trial also measured levels of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and cardiovascular risk. Patients on tirzepatide vs placebo showed significant decreases in hs-CRP, further supporting the idea that GLP-1 receptor agonists could be tackling sleep apnea on multiple fronts.1
Anti-Inflammatory Effects
In addition to promoting weight loss, GLP-1 receptor agonists may improve sleep apnea through their anti-inflammatory effects, which could play a key role in reducing airway obstruction and enhancing overall sleep quality.
Chronic low-grade inflammation is a common issue among people with obesity and sleep apnea, contributing to airway swelling and frequent breathing interruptions during the night. The root of this inflammation often stems from a vicious cycle tied to OSA itself, Dr Malhotra explains.
“When the airway repeatedly collapses, oxygen levels drop, and that triggers inflammation,” he says. “That inflammation, in turn, makes the airway more prone to obstruction. Breaking that cycle — whether by addressing weight, hypoxia, or both — can result in significant improvements.”
Reducing inflammation may do more than open airways — it could also help improve overall sleep quality. Dr Rodrigueznotes that patients with high levels of systemic inflammation often struggle with poor sleep beyond their breathing issues.
“Inflammation interferes with normal sleep regulation,” he says. “When you can bring it down, you’re not just improving breathing — you’re helping the body get more restorative sleep.”
GLP-1 receptor agonists’ impact on sleep may also be tied to their ability to regulate energy metabolism and stabilize glucose levels. Sleep and metabolism are closely intertwined, as the body’s circadian rhythms help to regulate both processes.3 Disruptions in one system can spill over into the other, which is why people with conditions like type 2 diabetes often experience poor sleep.
“Better glucose control could improve circadian rhythms and lead to more stable sleep patterns,” Dr Malhotra says. “We didn’t measure circadian effects directly in the SURMOUNT-OSA trial, but it’s a potential mechanism worth exploring in future studies.”
Researchers are also investigating the potential for GLP-1s to affect rapid eye movement (REM) sleep, the phase of sleep associated with memory consolidation and emotional regulation. While this link has not been fully proven in clinical trials, Dr Malhotra adds that it’s an area worthy of further exploration.
“What happens to REM sleep and circadian rhythms, I don’t really know,” he notes. “Those weren’t pre-specified outcomes in this trial, but it’s something worth studying further.”
GLP-1s’ Effects on Mental Health
Another intriguing benefit is the medication’s potential to improve mental health. Study findings have shown GLP-1 receptor antagonists can reduce anxiety and depression, likely due to their effects on neurotransmitters and inflammatory pathways in the brain.4 Since sleep and mental health are deeply connected, any improvements in mood could indirectly lead to better sleep, Dr Rodriguez says.
“We know that stress and anxiety are major contributors to insomnia and sleep disturbances,” he says. “By improving mood and reducing stress, GLP-1s could help patients fall asleep more easily and stay asleep longer.”
Although research in this area is still emerging, doctors suspect GLP-1s provide neuroprotective properties that could slow the progression of neurological conditions such as Alzheimer disease, Dr Malhotra says.
“There’s a theory that these medications may reduce the accumulation of tau proteins in the brain,” he says. “It’s speculative for now, but if proven true, it could open up new possibilities for treating sleep disorders linked to neurodegenerative diseases.”
Why GLP-1s Aren’t a Magic Bullet
Despite the medication’s many potential benefits, experts caution that GLP-1s are not a standalone solution for sleep apnea, and they are not appropriate for everyone with the condition.
One key limitation is that GLP-1 receptor agonists primarily work by addressing excess weight, which is not the root cause of sleep apnea for all patients. Some 20% of adults with OSA are considered non-obese, meaning they do not fall into the overweight or obese category on the basis of their BMI.5 Facial structure, for example, can play a significant role in narrowing the airway, regardless of body weight.6
“Some people have sleep apnea because they have small, narrow airways or a recessed jaw,” Dr Malhotra says. “In those cases, weight loss won’t fix the problem, and medications like this aren’t the right fit.”
Sleep apnea also affects children, but the underlying causes and treatment strategies often differ. “In kids, enlarged tonsils and adenoids are often the problem,” Dr Malhotra says. “We wouldn’t be using GLP-1 receptor agonists in those cases. This treatment is specifically for adults with obesity-related sleep apnea.”
Also, for optimal results, patients who are prescribed GLP-1s still need to combine the therapy with lifestyle changes like regular exercise and healthy eating. Without those changes, patients risk losing lean muscle mass along with fat, which could undermine their long-term health, Dr Rodriguez says.
“The goal is to help patients lose weight and potentially come off CPAP, but that doesn’t happen overnight,” he adds. “It’s a process that requires commitment.”
What’s on the Horizon?
As researchers continue to study the ways GLP-1 receptor agonists influence sleep, there is growing optimism that these medications could reshape the treatment landscape for OSA and beyond.
“This is just the beginning,” Dr Malhotra says. “We have a new tool for managing sleep apnea, but we’re also learning how it may help with insomnia, anxiety, and even neurodegenerative conditions. There’s a lot more to explore.”
For now, though, the focus remains on integrating GLP-1 inhibitor therapy into standard care for OSA patients — while managing expectations.
“Obesity is a disease, and it requires a comprehensive approach,” Dr Rodriguez says. “GLP-1s are a game-changer, but they’re not magic. Patients need to understand that GLP-1s work best as part of a comprehensive plan.”
“They should be working with a nutritionist, increasing physical activity, and thinking long-term. It’s not just about losing weight quickly — it’s about maintaining that weight loss and improving overall health. We know that once patients stop taking these medications, they can regain a significant portion of the weight. That’s why it’s critical to address the underlying lifestyle factors.”
