 Atul Malhotra, MD

Credit: University of California, San Diego

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 (

 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.

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

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.

: 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?

 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.

: So tirzepatide led to substantial improvements in the SURMOUNT trials. How do you see this therapy fitting into the current OSA treatment landscape?

 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.

: 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?

 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.

: 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?

 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.

: What patient phenotypes do you believe are the most are most likely to benefit from tirzepatide for OSA?

 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.

: If tirzepatide becomes a widely adopted treatment for OSA, how might that affect long term adherence to CPAP therapy?

 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.

: How do you see pharmacologic therapies likely to improving or possibly complicating OSA care globally, particularly when CPAP therapy may be unaffordable or unavailable?

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.

: What are the most important questions that still need to be answered about how GLP-1 therapies modulate sleep-disordered breathing?

 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?

: Where do you see the future of OSA care heading?

 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.

Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. 

. 2024;391(13). doi:https://doi.org/10.1056/nejmoa2404881

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

Articles

Tirzepatide, a GLP-1 receptor agonist, has shown promise in treating obstructive sleep apnea (OSA) by inducing significant weight loss and improving apnea-hypopnea index, oxygenation, and other health markers. The FDA's approval of tirzepatide for OSA has increased interest and referrals for OSA diagnosis and treatment. While CPAP remains the first-line therapy, tirzepatide offers an alternative for those unable to use CPAP. Ongoing research is needed to understand long-term effects, cardiovascular benefits, and the potential for personalized treatment approaches in OSA care.

In this Q&A, Malhotra discusses how tirzepatide impacts obstructive sleep apnea treatment.

Tirzepatide’s Impact on OSA, With Atul Malhotra, MD

Tirzepatide Is A ‘Ray of Hope’ for Patients with OSA: Referral Uptick, Who Benefits 

Ever since the US Food & Drug Administration (FDA) approved tirzepatide (Zepbound) for 

 last December, there has been an increase in OSA referrals.

Tripeptide’s FDA approval, announced by Eli Lilly and Company on December 20, 2024, was based on positive findings from the Phase 3 SURMOUNT-OSA clinical trial.

 The pivotal trial assessed tirzepatide (10 mg or 15 mg), a dual-activating glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 agonist, in 469 adults with OSA and obesity over 52 weeks. Among this patient population, tirzepatide provided significant improvements in the apnea-hypopnea index, oxygenation, patient-reported outcomes, blood pressure, and C-reactive protein levels.

Participants on tirzepatide achieved an average of up to 20% weight loss and experienced ≥ 25 fewer breathing interruptions for each hour slept (

Among patients not on PAP therapy, tirzepatide was approximately 5 times more effective than placebo in reducing breathing disruptions. Tirzepatide led to 25 fewer hourly breathing disruptions, compared with 5 in patients on placebo. For those on PAP therapy, tirzepatide brought 29 fewer hourly breathing disruptions, compared with 6 for placebo.

Tirzepatide continued to demonstrate improvements at 1 year, with approximately 42% of adults treated with tirzepatide and 50% of adults on tirzepatide and PAP therapy experiencing remission or mild, non-symptomatic OSA. Whereas in the placebo arm, 16% and 14% experienced remission or non-symptomatic OSA, respectively.

Tirzepatide is the first and only prescription medicine available for adults with moderate-to-severe OSA and obesity, and since its approval, OSA awareness has risen among patients and healthcare providers. GLP-1s have driven attention to this previously underrecognized and undertreated sleep disorder.

“We're seeing lot of lots and lots of patients who are inquiring about GLP-1s as one of the potential treatment options for obstructive sleep apnea, and we also seeing that it has raised the awareness of sleep disorders, particularly obstructive sleep apnea,” Atul Malhotra, MD, lead investigator of the SURMOUNT-OSA trial and sleep medicine specialist at UC San Diego Health, told 

 spoke with 4 experts regarding GLP-1’s impact on sleep apnea, receiving insight from specialists in sleep medicine, pulmonology, and otolaryngology.

“A lot of the patients that do suffer from obstructive sleep apnea are overweight, and so their body mass index is an important component that's contributing to their disease, but there's a lot of patients that come into our practices that don't have weight issues, or that have weight issues and have additional structural issues, so I think it really just has to be thought of as a tool,” said Brian Weeks, MD, an ENT-Otolaryngologist is at Senta Clinic, during an interview with 

 “Now, obviously, for overweight patients, it's a ray of light, it's a ray of hope for them, but it's one tool in the armamentarium that we have.”

(sleep medicine and pulmonary medicine specialist)

Relevant disclosures: Malhotra (Eli Lilly and Company, LivaNova USA, ZOLL Respicardia, Itamar Medical, Avadel CNS Pharmaceuticals, Axsome Therapeutics, JAZZ Pharmaceuticals), Weeks (Stryker Corporation), Walia (Eli Lilly and Company, Resmed Corp, JAZZ Pharmaceuticals, Boston Scientific Corporation, Itamar Medical, Harmony Biosciences, Lilly USA, Fisher & Paykel Healthcare, Novo Nordisk, Merck Sharp & Dohme), and Kundel (ZOLL Respicardia, Eli Lilly and Company).

Iapoce, C. FDA Approves Tirzepatide for Obstructive Sleep Apnea in Obesity. Hcplive.com. Published December 20, 2024. Accessed September 25, 2025. 

https://www.hcplive.com/view/fda-approves-tirzepatide-for-obstructive-sleep-apnea-in-obesity

. 2024;391(13):1193-1205. doi:10.1056/NEJMoa2404881

Videos

FDA approval of tirzepatide for OSA sparks a surge in referrals as experts highlight weight loss benefits, symptom relief, and patient selection.

Tirzepatide Is A ‘Ray of Hope’ for Patients with OSA: Referral Uptick, Who Benefits

Weight Loss May Be Key to Resolving OHS, Says Atul Malhotra, MD 

, the 39th annual meeting of the Associated Professional Sleep Societies in Seattle, Atul Malhotra, PhD, a sleep medicine specialist at UC San Diego Health, presented “Obesity Hypoventilation Syndrome - Updates in Diagnosis, PAP, and Weight Management” on June 10th in Seattle. HCPLive sat down with Malhotra at the meeting to discuss updates in weight management for 

In the first half of the interview, Malhotra shared OHS updates regarding diagnosis and positive airway pressure (PAP), which can be viewed

. He discussed how, despite OHS being a common issue, arterial blood gases are not checked as often as they used to be.

However, examining serum bicarbonate is helpful for identifying OHS, a disorder that often worsens the prognosis of obstructive sleep apnea (OSA). OHS and OSA tend to occur at the same time with a raised bicarbonate level.

Many patients with OHS do not find relief with PAP. Even though Malhotra offered suggestions to improve PAP adherence—patient education, intensive support, maintaining nasal pain—he said weight management is the most helpful.

“Data suggest you need to lose about 25 or 30% [of] your body weight to resolve obesity hypoventilation syndrome,” Malhotra said.

Malhotra conducted a big clinical trial recently that showed appetite therapy was helpful in improving OSA and cardiovascular symptoms, such as systolic blood pressure, reactive protein sleep apnea, and hypoxic burden. In that study, weight loss of 18 to 20% was substantial.

“So, if I started 200 pounds, 20% weight loss would be 40 pounds, or bring me 260 pounds, quite a game changer for those patients,” Malhotra said. “But given the need [of] 25% - 30% weight loss to resolve obesity hypoventilation syndrome... current data suggests that your tirzepatide may not be enough to get you to resolution of that subset of patients.”

Malhotra highlighted another drug in the pipeline—retatrutide (Triple G), a GLP-1 with a glucagon agonist. He said that retatrutide looks promising in preliminary studies, providing up to 25% of weight loss.

“That might be what we need to see [for] resolution of obesity hypervalent syndrome, but bottom line is, we need more data,” he said.

Relevant disclosures for Malhotra include Eli Lilly and Company, LivaNova, Itamar, ZOLL Respicardia, Impulse Dynamics, Jazz Pharmaceuticals, and Eisai Inc.

Nowalk N, Malhotra A, Mokhlesi B, et al. Obesity Hypoventilation Syndrome - Updates in Diagnosis, PAP, and Weight Management. Presented at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies, on Tuesday, June 10 in Seattle.

At SLEEP 2025, Malhotra emphasized the need for weight loss to resolve obesity hypoventilation syndrome and highlighted limitations of current therapies.


Updates in Obesity Hypoventilation Syndrome Diagnosis, with Atul Malhotra, MD

Atul Malhotra, MD, a sleep medicine specialist at UC San Diego Health, presented “Obesity Hypoventilation Syndrome - Updates in Diagnosis, PAP, and Weight Management” at 

SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies

HCPLive sat down with Malhotra at the meeting to discuss these new updates and what they mean for 

 care. He talked about the most important updates in the diagnostic criteria or clinical approach to identify OHS in 2025 and what’s new in the management of OHS with positive airway pressure (PAP) therapy.

“We don't check as many arterial blood gases as we used to, and I think there's increasing awareness that obesity hypoventilation syndrome is a common problem, particularly [in] the sleep clinic,” Malhotra said. “Body Mass Index is 40, about a 30% prevalence of obesity. [With] obesity hypoventilation syndrome, if your body mass index is 50, it's about a 50% prevalence of obesity. Looking at the serum bicarbonate can be quite helpful, and high clinical suspicion can be quite helpful as well.”

He explained that when the bicarbonate level is elevated, obstructive sleep apnea (OSA) and OHS often coexist. OHS worsens the prognosis of OSA, leading to poor outcomes.

“[Assessing] blood gas during the daytime can be quite helpful because it's elevated in patients with obesity hypoventilation syndrome and typically not elevated in obstructive sleep,” Malhotra said.

Capnometry via an app can also be helpful. In clinical settings, experts have used polysomnography to measure carbon dioxide levels transcutaneously, but now patients have begun at-home capnometry through apps.

When bicarbonate rises, Malhotra said hypercapnia could be a cause, but also other influences such as steroids and diuretics. Glucocorticoids or thiazide diuretics can elevate bicarbonates via metabolic alkalosis.

“it's really not diagnostic of hypercapnia if you have a high bicarbonate, but should raise your clinical suspicion,” Malhotra said. “Especially if a bicarbonate is normal, it's less likely to be hypoventilation.”

When it comes to PAP, many patients have high adherence to this treatment, but do not feel any better.

“See, the usual things that we do in terms of PAP troubleshooting…You need to lose about 25 or 30% of your body weight to resolve hypoventilation syndrome,” Malhotra said. “Let's resolve the hypercapnia.”

At SLEEP 2025, Malhotra shared updates on diagnosing and managing OHS, including the role of bicarbonate, PAP use, and weight loss.