Tirzepatide (Zepbound®): Its Effects on Sleep Apnea in the Surmount-OSA Phase 3 Trial
- gcoakford
- Jun 8
- 6 min read
Key Takeaways
● Tirzepatide significantly reduced obstructive sleep apnea (OSA) severity in the Surmount-OSA clinical trial
● Tirzepatide is now FDA-approved to treat OSA in people with obesity
● It’s an add-on therapy, not a replacement for CPAP
● Patients also gained health benefits beyond sleep
● A personalized approach to treatment is essential
● Patients should discuss with their healthcare provider which treatment or combination of treatments is best for them
For people with sleep apnea and obesity, recent clinical research suggests that tirzepatide, sold under the brand names Zepbound® and Mounjaro®, may offer more benefit than weight reduction alone. A new study shows that tirzepatide could also improve or even significantly reduce obstructive sleep apnea (OSA) symptoms in certain patients.
To find out more about tirzepatide and its potential promise for sleep apnea patients, Alliance of Apnea Partners President (ASAP) and CEO Dr. Monica Mallampalli, PhD, and Italian Apnoic Association President Luca Roberti hosted an online discussion with Dr. Atul Malhotra, MD, research chief of Pulmonary, Critical Care and Sleep Medicine at US San Diego. Dr. Malhotra led the Surmount-OSA clinical trial team that tested tirzepatide for the treatment of sleep apnea and is the lead author of the research paper detailing the team’s findings.
“Treating both sleep apnea and obesity is better than treating either one alone.”
The trial was funded by Eli Lilly and Company, the pharmaceutical company that developed tirzepatide.
The online discussion, which took place before the Food and Drug Administration (FDA) approved tirzepatide for the treatment of patients with sleep apnea in December of 2024, is available to watch here.Here’s what you need to know.
What Is Tirzepatide—and Why Are Sleep Doctors Interested in It?
Tirzepatide combines two synthetic hormones, GLP-1 agonist and GIP, that increase insulin sensitivity and decrease appetite. Tirzepatide is the first of these drugs approved by the Food and Drug Administration (FDA) for managing sleep apnea.
That’s a welcome step for sleep apnea patients, who are eager to see new treatment innovations. For decades, continuous positive airway pressure (CPAP) has remained the gold-standard therapy for sleep apnea patients, but some patients find it difficult to adhere to CPAP therapy. A recent safety-related recall of Philips-manufactured CPAP machines also caused many patients to become wary of using the devices, highlighting the importance of bringing new therapies to the market.
“We support innovation because we believe that patients need options for treatment and to manage their sleep apnea,” said Dr. Mallampalli. “At the same time, we need these treatments to be safe and effective. We do not believe one size fits all. … We look forward to a future where there is a personalized approach to treatments.”
In June 2024, researchers submitted data to the FDA seeking approval for tirzepatide as a treatment for sleep apnea in people with obesity. After granting it a fast-track designation to Eli Lilly, the FDA approved tirzepatide for that use in December 2024.
What the Surmount-OSA Study Revealed
The Surmount-OSA study was a 52-week, randomized, double-blind, placebo-controlled clinical trial. It included two groups of adults with moderate to severe OSA and obesity: one group who were not using CPAP therapy, and one group who were using CPAP.
All participants had a body mass index (BMI) over 30, and most had severe sleep apnea with an apnea-hypopnea index (AHI) around 50 at baseline. The AHI is the average number of times a patient stops breathing (apnea) or has abnormally shallow breathing (hypopnea) in an hour.
The results Dr. Malhotra and his team described were striking. In the CPAP group, about 72% saw at least a 50% drop in AHI. Roughly 40–50% of patients improved to a level that might no longer require CPAP, depending on other symptoms and severity.
Patients also experienced:• Average weight loss of 18–20% over one year• Significant reductions in high-sensitivity C-reactive protein, a marker of cardiovascular risk• Lower systolic blood pressure• Better daytime alertness and nighttime sleep quality, according to patient-reported sleep scores
Dr. Malhotra noted that some patients who received tirzepatide in the trial achieved an apnea hypopnea index of less than five or between five and 14 without daytime sleepiness--a significant improvement.
A New Era for Treating Sleep Apnea?
For the millions of people managing both obesity and obstructive sleep apnea, tirzepatide may offer a welcome approach to help reduce symptoms and improve overall health and quality of life. But it’s not the only potential solution, and Dr. Mallampalli cautioned that patients should not just drop CPAP treatment and try tirzepatide instead in the hope of a dramatically improved outcome. Dr. Malhotra noted that existing research has suggested that, even before the advent of tirzepatide, weight loss and CPAP combined were more effective than CPAP alone.
So patients and healthcare providers should consider what therapy or combination of therapies might work best for an individual with sleep apnea.
“It adds to the existing therapies for sleep apnea,” Dr. Malhotra said of tirzepatide. “Just giving people CPAP and ignoring their body weight is not a good idea. Diet, exercise, and sleep are the three pillars of health. Existing obstructiveon sleep apnea therapies work well. We didn't compare CPAP to tirzepatide, and so it's not that tirzepatide is better or worse than CPAP. It's an extra therapy, but not a replacement.”
What This Means for Sleep Apnea Patients With Obesity
Tirzepatide might be the first medication to directly reduce the severity of OSA by addressing one of its primary causes: excess weight. But it’s not a standalone solution or a CPAP replacement. It’s part of an evolving treatment toolkit.
“We didn’t compare CPAP to tirzepatide,” Dr. Malhotra emphasized. “It’s an extra therapy, but not a replacement. … Treating both sleep apnea and obesity is better than treating either one alone.”
For patients who can’t tolerate CPAP or have struggled with lifestyle-based weight loss alone, this could represent a significant new option. It remains important for patients to discuss their treatment options with their healthcare providers to determine what Dr. Mallampalli stresses should be “the right treatment for the right patient.”
Side Effects
Tirzepatide’s most commonly reported side effects have included nausea, vomiting, and diarrhea. But the Surmount-OSA trial’s study reported two cases of mild pancreatitis in the tirzepatide group. “There may be something called ascertainment bias,” Dr. Malhotra said, where symptoms like nausea prompt more frequent testing. Malhotra said that, after careful review of these, he did not find them unduly worrying.
Overall, “the safety and tolerability profile of tirzepatide in people with moderate to severe sleep apnea and obesity was generally consistent with the safety profile in people with obesity,” Dr. Malhotra said.
The Future: Personalized Sleep Apnea Treatment
There are other treatments, including oral appliances, positional therapy, and potentially surgery, in some cases. Tirzepatide may now join the list, especially for patients with obesity who haven’t responded well to traditional therapies alone.
“These are exciting times for the sleep apnea community,” Dr. Mallampalli noted. “But I believe many patients are still not aware of all these innovations that are happening.”
Dr. Mallampalli also asked Dr. Malhotra whether his team has considered investigating additional analysis around males and females or sleep apnea patients of different ages.
“We do know from other literature that women lose more weight than do men with these GLP-1 receptor agonists,” Dr. Malhotra responded. “And why that's the case isn't entirely clear. Some people think it's just a matter of body size, the pharmacology … but that's a theory. Nobody knows.”
Dr. Malhotra also pointed to differences among the various Surmount studies. The Surmont One study saw about 21% weight loss, slightly more than the Surmount-OSA study found. “It could be that, because there are more women in Surmount One than there were in Surmount-OSA, they had more weight loss because we expect that with tirzepatide,” Dr. Malhotra said. “It could also be that their follow up was just over 70 weeks. [Ours in Surmount-OSA] was 52 weeks. It could be that the longer duration of follow up allowed more weight loss—ongoing, progressive weight loss—over time.
“But the other point to make is that people with diabetes tend to lose less weight than people without diabetes with tirzepatide,” he added. “The Surmount Two study that was [published] in ‘The Lancet’ a few years ago showed 13% to 14% weight loss, rather than 21%. So the fact that we excluded diabetics may have given more efficacy for tirzepatide.”
“What I believe clinically is that treating both sleep apnea and obesity is a good idea,” Dr. Malhotra concluded. “If diet and exercise don’t work, then we have tirzepatide as an option for improving weight loss.”
If you live with sleep apnea and obesity, talk to your healthcare provider about whether this new treatment might be right for you and how it might fit into a broader, more personalized care plan.
Read more about Zepbound and sleep apnea at the Alliance of Sleep Apnea Partners blog. Watch the online discussion between Dr. Atul Malhotra, Dr. Monica Mallampalli, and Luca Roberti here. For more sleep apnea information and resources, sign up for our newsletter at apneapartners.org/newsletters.
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