For years, individualized obstructive sleep apnea care has been more aspiration than routine practice. Pharmacologic therapies may help change that.
By Sree Roy
When the options are limited to devices or surgery, the clinical management of obstructive sleep apnea (OSA) is, in most cases, binary: either a patient adheres to CPAP therapy, or they seek an alternative, such as an oral appliance. Though polytherapy has existed, theoretically—a positional therapy device with CPAP, for example—regularly setting up, cleaning, and maintaining more than one device made it unappealing to some patients and physicians, who tended to rely on positive airway pressure devices as a solution for the masses. And while CPAP-only has proved effective for many, it fails to account for the complex, heterogeneous nature of OSA, and risks treatment abandonment when a single modality becomes insufficient or intolerable.
The emergence of pharmacologic treatments, specifically glucagon-like peptide-1 (GLP-1) receptor agonists and investigational compounds targeting airway physiology, is shifting this mindset. Stakeholders say these medications should be viewed as additional tools that will allow for a more nuanced, multi-modal approach to care, not necessarily as device replacements. This mirrors the management of other chronic conditions, such as hypertension or diabetes, where clinicians routinely combine therapies to address different underlying mechanisms.
“Rather than asking which single therapy is best, I think clinicians will increasingly ask which combination of therapies best addresses an individual patient’s underlying pathophysiology, symptoms, and overall risk profile,” says Taylor Treacy, MD, a postgraduate (year five) in pulmonary, critical care, and sleep medicine at The Mount Sinai Hospital.
Beyond ‘Either/Or’
Patients vary in their disease phenotypes—ranging from those driven primarily by obesity to those with impaired upper airway neuromuscular function or high loop gain.
According to Treacy, the field is moving toward a precision medicine approach where therapies are selected and potentially combined based on the specific factors driving a patient’s OSA. This transition is supported by recent clinical data, such as the SURMOUNT-OSA trials, which evaluated the GLP-1 receptor agonist tirzepatide (Zepbound) in adults with moderate-to-severe OSA and obesity.
The trials demonstrated that tirzepatide was significantly more effective than placebo in reducing breathing disruptions. In adults not on PAP therapy, the medication led to an average of 25 fewer breathing disruptions per hour, compared to five with placebo. For those already on PAP therapy, the reduction was even more pronounced, with an average of 29 fewer disruptions per hour.
“PAP therapy remains an effective treatment option, and Zepbound is not intended to replace it,” says an Eli Lilly spokesperson. “Instead, Zepbound provides an option for adults with moderate-to-severe OSA and obesity, supporting individualized treatment approaches based on the unique needs of each person.” Lilly continues to work with health care providers across specialties and facilities to ensure they can make educated, informed recommendations for their adult patients with obesity when prescribing Zepbound for moderate to severe OSA, the spokesperson adds.
Treacy notes that for patients who struggle with PAP adherence, the introduction of a medication could prevent them from feeling they have “failed” treatment.
“Combination therapy could help keep patients engaged in their care,” she says. “For example, a patient who initially cannot tolerate CPAP may begin treatment with a GLP-1 receptor agonist, lose weight, and experience improvements in symptoms or disease severity. After seeing that progress, they may be more willing to retry CPAP or another therapy that previously seemed overwhelming. Rather than viewing PAP intolerance as the end of the treatment journey, combination therapy reframes it as one component of a broader, individualized treatment strategy.”
GLP-1s Already Impacting Neurostimulator Evaluations
The integration of GLP-1s is already changing how surgeons evaluate candidates for interventions like hypoglossal nerve stimulation.
Generally, having a lower body mass index (BMI) makes people better candidates for neurostimulator therapy for OSA, says ENT-sleep surgeon Ofer Jacobowitz, MD, PhD, co-director of sleep at ENT and Allergy Associates. “The use of medications has become fairly prevalent, and yes, I am seeing patients who have shifted into a more favorable BMI category,” says Jacobowitz, chair of the sleep disorders committee of the American Academy of Otolaryngology. “Even if it’s the same patient with a BMI of 32 versus now 29 or 28, the patient is a much better candidate.”
However, complexities are also introduced. If a patient is currently on medication and expects further weight loss, they may be a more attractive candidate for surgery due to the higher probability of a beneficial outcome, Jacobowitz notes. Conversely, if a patient has already achieved maximal weight loss but discontinues the medication later, subsequent weight gain could counteract the surgical benefits.
A recent survey of 50 ENTs and 100 sleep specialists, supplemented by electronic health record data from approximately 2.8 million OSA diagnoses, was telling. It found that while there might be a short-term decrease in hypoglossal neurostimulator volumes as patients trial weight-loss medications, the long-term outlook suggests a net increase in people seeking alternatives to CPAP. In a SLEEP 2026 abstract, the authors (which include Jacobowitz) state: “The findings suggest that GLP-1 [receptor agonist]s are currently disrupting traditional OSA treatment patterns, and that these medications may expand the total pool of patients seeking treatment for CPAP-alternatives, ultimately increasing the [hypoglossal nerve stimulator]-BMI eligible population.”1
Sequencing Strategies
As the toolbox grows, the question for clinicians shifts from “if” to “when” and “how” to introduce options. Therapy sequencing should be individualized rather than dictated by a rigid algorithm, several stakeholders say.
While CPAP remains the first-line treatment for many due to its strong evidence base for reducing respiratory events and improving quality of life, clinicians are lowering the threshold for adjunctive therapies. This is particularly true for patients with persistent symptoms, residual disease, or difficulty tolerating CPAP.
“The question should shift from ‘What should I use instead of CPAP?’ to ‘What additional therapy addresses the remaining drivers of this patient’s disease?'” Treacy says.
For some patients, a GLP-1 might be the first step, especially if weight loss is a primary goal. For others, investigational drugs like Apnimed’s AD109, which targets upper airway muscle tone rather than weight, may eventually, if approved by the Food and Drug Administration, provide a solution for non-obese phenotypes. Jacobowitz views this as a “rational, advanced treatment” model. He compares it to cardiovascular care, where a patient isn’t just given one pill but a spectrum of treatments—lifestyle changes, multiple medications, and perhaps a device—to achieve success.
The survey data supports this trend: sleep specialists are already utilizing GLP-1s in 29% of first-line OSA treatments. When CPAP is the primary therapy, GLP-1s are used as an adjunct in approximately 50% of patients. This suggests that the “polytherapy” model is already taking root in clinical practice, even as many physicians continue to trial the medications to determine their long-term role.1
Multidimensional Strategy for Success
The shift toward polytherapy necessitates a reevaluation of how “success” is measured in sleep medicine. For decades, the apnea-hypopnea index (AHI) has been the primary metric for diagnosis and treatment efficacy. However, experts argue that AHI alone does not capture the full clinical picture.
“Two patients with the same AHI may have very different symptom burdens, oxygen desaturation profiles, and long-term cardiovascular risk,” Treacy says. She advocates for a multidimensional endpoint strategy that keeps AHI in the frame but also includes:
- hypoxic burden: measuring the depth and duration of oxygen desaturations.
- sleep quality and daytime functioning: prioritizing patient-reported outcomes.
- cardiometabolic markers: tracking blood pressure, high-sensitivity C-reactive protein, and weight.
- long-term cardiovascular events: assessing the ultimate impact on mortality and morbidity.
Jacobowitz adds, “Finally, the AHI is not looked at as the true target. I think there’s a greater understanding of the physiology of sleep apnea, and other measures that are being used now, which include the hypoxic burden, will be very useful for risk prediction.”
Practical Realities
Despite the enthusiasm for pharmacologic options, several practical hurdles remain for widespread adoption in sleep clinics. Prescribing GLP-1s requires a significant administrative framework for which many sleep practices are not equipped.
Jacobowitz points out that managing these drugs involves staffing expenses for pre-approvals and frequent dose adjustments at first—an uncompensated expense. Additionally, some sleep specialists may be hesitant to manage medications that also impact hypertension or diabetes, preferring to defer to primary care physicians or endocrinologists.
However, prescribing GLP-1s “could increase patient visits and be a positive aspect to attract more patients to the practice. And so some doctors may want to prescribe for that reason,” he says.
The issue of treatment persistence for GLP-1s is critical. Experience shows that weight relapse often occurs after the discontinuation of GLP-1 medications, whether discontinuing be due to insurance changes, intolerance, or other reasons. This “potential pitfall” must be factored into the long-term management plan, especially when the medication is used to make a patient eligible for a permanent surgical intervention.
The Future of OSA Therapies
In the future, the typical treatment plan for a newly diagnosed OSA patient is unlikely to follow the linear path of the past. Instead, it will likely resemble a precision medicine model that prioritizes each patient’s phenotype.
“The defining change over the next five years will not be that OSA is routinely treated with polytherapy, but that it is treated with the same level of individualization that has transformed the management of other chronic diseases,” Treacy says.
A next step will be generating evidence to identify which combinations are truly synergistic. The field still needs data to determine which patients benefit most from specific pairings—such as CPAP plus a GLP-1 versus an oral appliance plus an airway-targeting medication.
For now, the introduction of popular drugs for OSA allows clinicians to move beyond the limitations of single-device therapy. By embracing a more complex, multi-modal approach, the field is positioning itself to better address the diverse needs of the millions of patients living with sleep-disordered breathing. As Jacobowitz proclaims, the ultimate goal remains: “We want, of course, to reduce medical risk, but at the same time, listen to the patients and adapt the treatment that best fits, based on their preference and their physiological characteristics.” With the addition of pharmacotherapies, it is becoming easier to do just that.
Reference
1. Mack K, Briggs A, O’Brien T, et al. 0653 Integration of GLP-1 receptor agonists into treatment protocols for obstructive sleep apnea. Sleep. 2026 May;49(supp_1):A290.
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