August 8, 2024 | Obstructive sleep apnea (OSA) is a sleep disorder associated with major cardiovascular complications. Despite being a common sleep disorder, there has not been an effective drug treatment for patients. Fortunately, a team from the University of California San Diego School of Medicine recently published a drug repurposing study that may offer hope.
“There’s about a billion people worldwide affected by sleep apnea,” says Atul Malhotra, MD, professor of medicine at University of California San Diego School of Medicine, director of sleep medicine at UC San Diego Health, and lead author of the study. He and his team may have a lead in treating OSA. They found that tirzepatide, a medication used to treat Type 2 Diabetes and as a weight loss drug, may be the key to the first drug therapy for sleep apnea (The New England Journal of Medicine, DOI: 10.1056/NEJMoa2404881).
Tirzepatide’s Effects on OSA
Obesity is the most common reversible risk factor for OSA, according to Malhotra. As such, weight loss is helpful with reducing symptoms of sleep apnea. To determine the effectiveness of tirzepatide, the team conducted two Phase 3, double-blind, randomized, controlled trials with adult participants with moderate to severe OSA and obesity (The New England Journal of Medicine, DOI: 10.1056/NEJMoa2404881). Those who did not use continuous positive airway pressure (CPAP) therapy were enrolled in the first trial while those who used CPAP therapy were enrolled in the second trial. Each participant was administered a maximum tolerated dose of 10mg or 15mg of tirzepatide versus a placebo and monitored over 52 weeks.
The results from both trials showed significant improvement in the Apnea-Hypopnea Index, the standard metric of sleep apnea severity. There were also concomitant improvements in body weight (about 18-20% loss, depending on the study arm), C-reactive protein, and hypoxic burden. Additionally, participants reported improved sleep-related outcomes and physically feeling better. Malhotra was also pleasantly surprised to see the magnitude of the significant improvement in systolic blood pressure.
However, he warns, as with all medication, about the potential side effects of tirzepatide, including nausea, vomiting, and diarrhea. Thankfully, these side effects are usually mild, and most of them went away by the end of the one-year study.
Malhotra is not sure if tirzepatide is effective primarily through weight loss or another mechanism. More studies are needed.
For clinicians and physicians, the study's results prove there is an additional treatment option to offer patients not just for OSA, but also for cardiometabolic risk. “Treating the whole patient is not just giving them a CPAP mask or diet and exercise instructions.” Malhotra believes the drug can serve as a complement to existing therapies such as CPAP.
“It’s an exciting time,” he says. “We’re getting some hard outcomes data, suggesting they’re not just losing weight cosmetically. We’re actually improving the health of patients and their outcomes.”