An international collaboration has suggested that tirzepatide, known to manage type 2 diabetes, could be the first effective drug therapy for obstructive sleep apnoea (OSA).
The results led by researchers from the University of California San Diego School of Medicine highlight the treatment's potential to improve the quality of life for millions around the world affected by OSA, said the authors, in The New England Journal of Medicine.
“The study marks a significant milestone in the treatment of OSA, offering a promising new therapeutic option that addresses both respiratory and metabolic complications,” said Atul Malhotra, MD, lead author, professor of medicine at University of California San Diego School of Medicine and director of sleep medicine at UC San Diego Health.
OSA can result in reduced oxygen levels in the blood and can also be associated with an increased risk of cardiovascular complications, like hypertension and heart disease.
Recent studies, also led by Malhotra, suggest that the number of OSA patients worldwide is close to 936m.
Conducted in two phase 3, double-blinded, randomised, controlled trials, the latest study cohort involved 469 participants diagnosed with clinical obesity and moderate-to-severe OSA. They were recruited from sites in nine countries, including the US, Australia and Germany.
Participants either used or did not use continuous positive airway pressure (CPAP) therapy, the most common sleep apnoea treatment which uses a machine to maintain an open airway during sleep, preventing interruptions in breathing.
Patients were administered either 10mg or 15mg of the drug by injection or a placebo. The impact of tirzepatide was evaluated over 52 weeks.
Researchers found that tirzepatide led to a significant decrease in the number of breathing interruptions during sleep, a key indicator used to measure the severity of OSA. This improvement was much greater than what was seen in participants given a placebo.
Importantly, some participants who took the drug reached a point where CPAP therapy might not be necessary.
Considerable data suggest that a drug therapy that targets both sleep apnoea and obesity is beneficial, rather than treating either condition alone.
Additionally, the drug therapy improved other aspects related to OSA, such as reducing the risk factors of cardiovascular diseases and improved body weight. The most common side effect reported was mild stomach issues.
“Historically, treating OSA meant using devices during sleep, like a CPAP machine, to alleviate breathing difficulties and symptoms,” Malhotra said. “However, its effectiveness relies on consistent use. This new drug treatment offers a more accessible alternative for people who cannot tolerate or adhere to existing therapies.
“We believe the combination of CPAP therapy with weight loss will be optimal for improving cardiometabolic risk and symptoms. Tirzepatide can also target specific underlying mechanisms of sleep apnoea, potentially leading to more personalised and effective treatment.”
Malhotra added that having a drug therapy for OSA represents a significant advancement in the field.
“It means we can offer an innovative solution, signifying hope and a new standard of care to provide relief to countless patients and their families who have struggled with the limitations of existing treatments. This breakthrough opens the door to a new era of OSA management for obese people, potentially transforming how we approach and treat this pervasive condition on a global scale.”
The next steps include conducting clinical trials to examine longer term effects of tirzepatide.
Study details
Tirzepatide for the treatment of obstructive sleep apnea and obesity
Atul Malhotra, Ronald Grunstein, Scott Sands, et al for the SURMOUNT-OSA Investigators.
Published in The New England Journal of Medicine on 21 June 2024
Abstract
Background
Obstructive sleep apnoea is characterised by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment.
Methods
We conducted two phase 3, double-blind, randomised, controlled trials involving adults with moderate-to-severe obstructive sleep apnoea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnoea–hypopnea index (AHI, the number of apnoeas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure.
Results
At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in metres) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was −25.3 events per hour (95% confidence interval [CI], −29.3 to −21.2) with tirzepatide and −5.3 events per hour (95% CI, −9.4 to −1.1) with placebo, for an estimated treatment difference of −20.0 events per hour (95% CI, −25.8 to −14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was −29.3 events per hour (95% CI, −33.2 to −25.4) with tirzepatide and −5.5 events per hour (95% CI, −9.9 to −1.2) with placebo, for an estimated treatment difference of −23.8 events per hour (95% CI, −29.6 to −17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity.
Conclusions
Among persons with moderate-to-severe obstructive sleep apnoea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes.
NEJM article – Tirzepatide for the Treatment of Obstructive Sleep Apnoea and Obesity (Open access)
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