GLP-1 Agonists Tied to Lower Mortality in HCM With Sleep Apnea

Adults with hypertrophic cardiomyopathy (HCM) and obstructive sleep apnea (OSA) who were treated with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) experienced roughly 30% fewer major adverse cardiovascular events (MACEs) over long-term follow-up than matched peers who were not, according to a real-world cohort study presented at the European Society of Cardiology (ESC) Congress 2026 in Munich and accepted for publication in JACC: Advances. The association was driven almost entirely by lower all-cause mortality, a finding that pharmacists are increasingly likely to field questions about as GLP-1 RA use expands well beyond diabetes and weight management.¹

Why HCM and OSA Together Raise the Stakes

Sleep-disordered breathing is common in HCM, and its presence tracks with worse disease. In a contemporary cohort evaluated by polysomnography, OSA was frequent and associated with adverse structural and physiologic changes, including higher left ventricular mass index and worse diastolic function. Greater OSA severity has also been linked to more nonsustained ventricular tachycardia in obstructive HCM. Current American Heart Association/American College of Cardiology guidance recommends assessing patients with HCM for symptoms of sleep-disordered breathing and referring them for evaluation and treatment when it is present.^2-4

"Patients who have OSA and also have HCM seem to create a domino effect of bad outcomes over the long term," said Milind Desai, MD, MBA, FACC, FAHA, FESC, director of the Hypertrophic Cardiomyopathy Center at Cleveland Clinic and the study's corresponding author. Obesity, he noted, both worsens cardiovascular risk and drives OSA, making it a shared upstream target.

What the Real-World Analysis Found

Investigators used the TriNetX Global Collaborative Network to identify adults with both HCM and OSA, comparing those who started a GLP-1 RA after their HCM diagnosis with those who never received one. Patients with prior heart transplant, septal reduction therapy, or myectomy were excluded. After 1:1 propensity-score matching across demographics, comorbidities, medications, and laboratory values, 5372 patients remained in each group. Median follow-up was 677 days in the GLP-1 RA group and 505 days in the comparator group.¹

GLP-1 RA exposure was associated with a lower cumulative rate of MACEs—a composite of all-cause mortality, acute myocardial infarction (MI), and ischemic stroke—at 12.2% versus 16.8% (odds ratio [OR], 0.689; P < .001). Time-to-event analysis was consistent (hazard ratio [HR], 0.700; 95% CI, 0.645-0.761), with MACE-free survival at 10 years of 51.9% versus 38.1%.¹

A Signal Driven by Mortality

The composite difference was driven almost entirely by lower all-cause mortality: 8.7% versus 14.2% (OR, 0.579; HR, 0.534; 95% CI, 0.476-0.600). By contrast, cumulative rates of acute MI (6.6% vs 7.7%), ischemic stroke (0.3% vs 0.3%), acute heart failure hospitalization (8.5% vs 9.2%), and arrhythmic events (14.6% vs 13.0%) did not differ significantly between groups. The authors noted that HCM-related decompensation is often driven by diastolic dysfunction, left ventricular outflow tract obstruction, and atrial arrhythmias, which are mechanisms that may be less responsive to metabolic therapy over the period studied.¹

“We found the composite outcomes were significantly better in the GLP-1 group, and the majority of this was driven by a mortality benefit,” Desai said. “There was no significant difference in stroke, MI, or heart failure admission.” He cautioned that the null end points may partly reflect the limits of registry data. “It’s much easier to document death; you are either alive or you’re dead. Arrhythmias and heart failure admissions tend to be harder to ascertain as end points.”

How the Finding Fits Existing Evidence

The direction of the association aligns with randomized data. In the SELECT trial (NCT03574597), semaglutide (Ozempic, Wegovy; Novo Nordisk) reduced cardiovascular events in adults with overweight or obesity and established cardiovascular disease but without diabetes. In SURMOUNT-OSA (NCT05412004), tirzepatide (Mounjaro, Zepbound; Eli Lilly and Company) reduced OSA severity alongside body weight and blood pressure in patients with obesity and moderate-to-severe OSA—supporting the premise that therapies acting on shared cardiometabolic and sleep-related pathways could be relevant in this overlapping population.^5,6

Caveats and Counseling Points

The findings are observational and hypothesis-generating, the authors stressed, and cannot establish causality. Important confounders—HCM phenotype and severity, OSA severity, continuous positive airway pressure (CPAP) adherence, and longitudinal weight change—were not captured, and medication data did not reflect dose, duration, or adherence. The analysis also spanned multiple GLP-1 RA agents with differing efficacy profiles. For pharmacists, the practical points are familiar: reinforce adherence and dose titration, counsel on gastrointestinal tolerability, and make clear that a GLP-1 RA does not replace CPAP or guideline-directed HCM care. The authors called for dedicated randomized trials in this high-risk phenotype.¹

“These are what I would call hypothesis-generating ideas that have to be tested in a prospective study,” Desai explained. He urged a low threshold for sleep evaluation—”Once you identify it, you need to treat it aggressively”—and frame effective obesity therapy as a lever on the whole chain. “Obesity is a big deal, and sleep apnea is a big deal. If there's a way we can impact one that can directly or indirectly impact the other, we should be aggressively seeking that out.'“

REFERENCES

1. Shah S, Abusafia M, Sheashaa H, Jadam S, Ospina S, Kaelber D. GLP-1 receptor agonist use and long-term outcomes in hypertrophic cardiomyopathy with obstructive sleep apnea: a real-world cohort analysis. JACC Adv. Published August 27, 2026. doi:10.1016/j.jacadv.2026.102955

2. Karim S, Chahal A, Venkataraman S, et al. Prevalence and clinical implications of sleep apnea in hypertrophic cardiomyopathy. JAMA Cardiol. 2025;10(10):1024-1033. doi:10.1001/jamacardio.2025.2877

3. Wang S, Cui H, Song C, et al. Obstructive sleep apnea is associated with nonsustained ventricular tachycardia in patients with hypertrophic obstructive cardiomyopathy. Heart Rhythm. 2019;16(5):694-701. doi:10.1016/j.hrthm.2018.12.017

4. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy. Circulation. 2020;142(25). doi:10.1161/CIR.0000000000000937

5. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563

6. Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391(13):1193-1205. doi:10.1056/NEJMoa2404881