As weight-linked cases improve, the field is left to confront the patients whose condition stems from other mechanisms.

By Sree Roy

With Zepbound (tirzepatide), the first FDA-approved GLP-1 for obstructive sleep apnea (OSA), showing strong reductions in the apnea-hypopnea index (AHI) in patients with obesity,¹ it’s easy to see why the public misperception that OSA is simply a weight problem is being reinforced.

These drugs are a powerful tool. But their biggest impact may not be treating a subset of OSA patients—it may be forcing the field to look beyond weight. Obesity remains a key risk factor. But anatomy, age,² and other drivers get far less attention. As GLP-1s target adiposity, those neglected factors may finally come into focus.

A recent meta-analysis of four community cohorts found that most adults with OSA are not obese. Only 31.5% had obesity (BMI ≥30), while 44.4% were overweight (25 ≤ BMI < 30) and 23.5% were normal weight or underweight.³ As neuroscientist Elie Gottlieb, PhD, who was not involved in the study, notes, “Where this study adds the most value is in reminding the field that a treatment strategy anchored exclusively to weight loss—whether through GLP-1 receptor agonists, bariatric surgery, or lifestyle intervention—will leave a substantial portion of the OSA population without a clear therapeutic path.'”

This is where a new opportunity lies. By effectively addressing obesity-linked OSA for many (it reversed the condition in up to 50.2% of SURMOUNT-OSA trial participants), GLP-1s prescribed by primary care physicians and other specialists are clearing the decks, allowing sleep specialists to refocus on the patients whose condition is driven by other factors.

“For the remaining patients, particularly those who are overweight or normal weight, management must address the full spectrum of pathophysiological endotypes: craniofacial anatomy, muscle responsiveness, arousal threshold, and loop gain,” says Gottlieb, head of applied science at Sleep.ai. “The emergence of pharmacotherapies targeting these non-anatomical mechanisms, alongside continued refinement of phenotyping tools, offers hope that personalized treatment will soon extend well beyond weight management alone.”

Even in patients with obesity, GLP-1s can help unmask other drivers of OSA. Carlos Nunez, MD, chief medical officer at Resmed, offers a case in point. “I have sleep apnea, and I was obese. A little less than two years ago, my BMI was 31,” he says. “I’ve been on a GLP-1. I lost all of the weight, but my sleep apnea never went away….It’s my anatomy.”

Ironically, Nunez adds, the GLP-1 phenomenon may also be boosting adherence to traditional therapies. Unpublished Resmed data from nearly 2 million records show that patients prescribed both a GLP-1 and CPAP are about 11% more likely to start CPAP therapy than those prescribed CPAP alone. One explanation: patients who felt stigma around weight now have an effective tool, which may improve engagement with CPAP.

GLP-1s aren’t the end of the story for OSA; they may be the start of a new one. They are re-engaging a population in the healthcare system and, in doing so, have handed sleep medicine a golden opportunity to broaden its focus, refine the understanding of non-obesity-related OSA, and deliver more personalized care.

References

1. Malhotra A, Grunstein RR, Fietze I, et al; SURMOUNT-OSA Investigators. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024 Oct 3;391(13):1193-1205.

2. Boers E, Barrett MA, Benjafield AV, et al. Projecting the 30-year burden of obstructive sleep apnoea in the USA: a prospective modelling study. Lancet Respir Med. 2025 Dec;13(12):1078-86.

3. Esmaeili N, Gell L, Imler T, et al. The relationship between obesity and obstructive sleep apnea in four community-based cohorts: an individual participant data meta-analysis of 12,860 adults. EClinicalMedicine. 2025 Apr 23;83:103221.