In this Q&A, Atul Malhotra, MD, a board-certified pulmonologist and a sleep medicine specialist at the University of California, San Diego, discussed the impact tirzepatide (Zepbound), a glucagon-like-peptide-1 (GLP-1) agonist receptor, has on
Malhotra was the lead investigator of the phase 3 SURMOUNT-OSA trials, examining the efficacy and safety of tirzepatide (10 mg or 15 mg) for patients with OSA over 52 weeks. The trial showed participants on tirzepatide achieved an average of up to 20% weight loss and experienced ≥ 25 fewer breathing interruptions for each hour slept (P < .001).1,2 Tirzepatide provided significant improvements in the apnea-hypopnea index, oxygenation, patient-reported outcomes, blood pressure, and C-reactive protein levels.
The positive findings led the US Food & Drug Administration (FDA) to approve tirzepatide for OSA, announced by Eli Lilly and Company on December 20, 2024. Since then, sleep specialists have been seeing a surge in OSA referrals.
HCPLive had spoken with 4 experts on the rise of GLP-1s for OSA, who were, aside from Malhotra, Brian Weeks, MD, from Senta Clinic, Harneet Walia, MD, from Baptist Health South Florida, and Vaishnavi Kundel, MD, from Mount Sinai. The 4 perspectives can be watched in a separate article published on the site.
Below is the full interview with Malhotra, which addresses unanswered questions on this topic, how tirzepatide fits into the current OSA treatment landscape, and his predictions on where OSA care is heading.
HCPLive: There’s growing evidence that the interest in GLP-1 is prompting more OSA testing and diagnosis. Have you personally seen the shift in your own practice or in the data?
Malhotra: There is increasing awareness of the results of the SUMROUNT study. With increasing discussion in the public about potential treatments for sleep apnea, more and more people are seeking treatment. Historically, some people have avoided the diagnosis because they didn’t want to be treated for it. They’d heard about CPAP and didn’t know much about it, but [it] didn’t sound appealing to them. So now that there are new treatments available that are FDA-approved, I think there is some enthusiasm to go ahead and seek additional testing.
HCPLive: So tirzepatide led to substantial improvements in the SURMOUNT trials. How do you see this therapy fitting into the current OSA treatment landscape?
Malhotra: There are no direct comparisons between tirzepatide and CPAP, and so first-line therapy for sleep apnea is still CPAP…but [for] those who can’t or won’t use CPAP, tirzepatide [is] a reasonable option. The data suggests if you can treat either obesity or sleep apnea or both, it’s better [to] treat both, rather than either condition alone.
HCPLive: Could you discuss how weight loss via GLP-1 receptor agonism is impacting upper airway physiology, and whether this is reshaping how we understand OSA?
Malhotra: Obesity is the major risk factor for sleep apnea, particularly [a] reversible risk factor that you can potentially fix. People with sleep apnea tend to be heavier than those people without sleep apnea. And if people [with] sleep apnea lose weight, their sleep apnea tends to improve.
We published a meta-analysis just before SURMOUNT-OSA… suggesting that the more weight you lose, the more your apnea hypopnea index improves. Potentially, what tirzepatide is doing in these trials is inducing weight loss, which leads to improvement in sleep apnea. It probably has other effects as well. They’re off target effects [of] these medications that may impact blood sugar and blood pressure and whatnot. But at least, weight loss is a mechanism of improvement in some of the outcomes that we observe.
Was it teaching us about upper airway physiology? [This] is an ongoing discussion.
HCPLive: Given the potential of tirzepatide to improve OSA, independent of CPAP use, how might this availability influence their urgency or approach to diagnosing OSA in patients who are obese? How does it impact the urgency?
Malhotra: If I’m seeing a patient in clinic and they’re having profound symptoms, I can start them on CPAP more or less right away and get them feeling better right away. With tirzepatide, there can be a delay in terms of the approval process and inducing weight loss can take some time. The SURMOUNT-OSA study…had improvements at 1 year. And so, some of that can take time. Things like motor vehicle actions, for example, could occur during that time. And at least in theory, putting on CPAP right away might help to reduce the risk of those kinds of complications.
With starting tirzepatide versus placebo, you start to see separation even as early as 4 weeks. You do see some separation compared to the control group in terms of sleep apnea outcomes, and by 20 weeks, by 5 months, you start to see statistical significance. It’s not that everything is delayed to 1 year. You see improvements.
HCPLive: What patient phenotypes do you believe are the most are most likely to benefit from tirzepatide for OSA?
Malhotra: Yeah, those are ongoing analyses that we’re looking at in terms of who benefits the most. To get into [the SURMOUNT]-OSA study, you need an apnea hypopnea index [of] about 15 events per hour. That means a breathing problem, 1 every 4 minutes for moderate to severe sleep apnea. The people with the lowest apnea hypopnea index are the ones [who] tend to get into a range you consider in remission. That is a value below 5.
Now, who benefits in terms of cardiovascular risk…is a little bit less clear. We excluded people with diabetes in the SURMOUNT-OSA studies. I can’t draw conclusions about that, but some data suggest that even though people with diabetes lose less weight, which is appetite, than people without diabetes, they may have a bigger bang for the buck.
HCPLive: If tirzepatide becomes a widely adopted treatment for OSA, how might that affect long term adherence to CPAP therapy?
Malhotra: There are a couple ways to look at this. Number one is what’s called the healthy user effect. The healthiest patients tend to be the most educated, the highest socioeconomic status. They tend to listen to their doctor. They tend to be adherent [to] treatment. And so, we have some data saying that the patients who use the GLP-1 receptor agonists are also adherent [to] the CPAP, potentially, because that’s the most motivated patients and the ones who are seeking change, and so they tend to use their CPAP more, not less.
The other way to think about [it] is there are lots of patients coming out of the woodwork, and so we’ve estimated about a billion people worldwide with obstructive sleep apnea. That number is increasing, not decreasing, because of the obesity pandemic. And so, these drugs are having an impact, but we’re not going to run out of sleep apnea patients anytime soon.
HCPLive: How do you see pharmacologic therapies likely to improving or possibly complicating OSA care globally, particularly when CPAP therapy may be unaffordable or unavailable?
Malhotra: CPAP is relatively speaking of inexpensive therapy. Prescribing CPAP is not just cost-effective, but…actually cheaper to buy the machine than not because you save money with car accidents or other complications. Tirzepatide is also not cheap. The price has been coming down over time. When people have estimated the total cost of…paying for all these medications, it’s quite substantial.
On the other hand, tirzepatide has benefits as well. For example, people report that their food intake goes down. I have many patients [who] say there’s [fewer] meal[s] per day, and that saves them 20 bucks a day or $600 a month.
Economics are complex. Suffice to say, people say they can’t afford CPAP. Push back a little bit, saying, ‘Well, compared to what, because you can’t afford a motor vehicle accident either.’ People say [CPAP is] expensive. It is, but so is the alternative.
HCPLive: What are the most important questions that still need to be answered about how GLP-1 therapies modulate sleep-disordered breathing?
Malhotra: There are several questions that are outstanding. Number one is, our trial was a 1-year study, so what happens after five or 10 years? We don’t know. Potentially, people maintain the medication long term, and they sustain the benefits. Others may stop the medication, and the body weight may come back.
The second question is, if you did go head-to-head with tirzepatide versus CPAP versus the combination, that’s not been done in a prospective study…so that might be an outstanding question.
The third question might be regarding cardiovascular risk. Are we actually preventing stroke and heart attack, and other kinds of complications?
HCPLive: Where do you see the future of OSA care heading?
Malhotra: The future of sleep apnea care is not clear. I’ll make a couple predictions here. Number one is these wearable technologies… are becoming more and more common. The idea of doing one snapshot in time to get a sleep test only tells you about one point in time, and many patients, particularly those on GLP-1 receptor agonists, are moving targets, so doing serial testing over time may be quite helpful. Some patients find it highly motivating as they’re losing weight, for example, to follow the output from one of these wearables and look over time how things are changing.
Number two is, I think there will be some efforts at prevention. We think of diet, exercise, and sleep [as] the 3 pillars of health. If you ignore one, the other two will suffer. So, if you don’t eat well, you don’t sleep well, [and] if you don’t sleep well, you tend to eat crummy foods. If you don’t exercise, you don’t sleep as well.
The third thing [is] this idea of personalizing medicine. People don’t all get sleep apnea for the same reason, and people vary in how they manifest clinically. Some people have profound sleepiness. Some people have insomnia where they can’t sleep at night. They keep waking up because of their breathing. Other people have no symptoms at all. That one-size-fits-all all approach has sort of failed us, where there are probably some patients that really benefit from one particular intervention, others probably need a different intervention.
Relevant disclosures for Malhotra include Eli Lilly and Company, LivaNova USA, ZOLL Respicardia, Itamar Medical, Avadel CNS Pharmaceuticals, Axsome Therapeutics, JAZZ Pharmaceuticals.
References
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Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. New England Journal of Medicine. 2024;391(13). doi:https://doi.org/10.1056/nejmoa2404881
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Derman C, Malhotra A, Walia H, Weeks B, Kundel V. Tirzepatide Is A “Ray of Hope” for Patients with OSA: Referral Uptick, Who Benefits. HCPLive. Published September 25, 2025. Accessed September 29, 2025. https://www.hcplive.com/view/tirzepatide-is-a-ray-of-hope-for-patients-osa-referral-uptick-who-benefits