Eli Lilly's tirzepatide, the active ingredient in type 2 diabetes medication Mounjaro and weight loss treatment Zepbound, has demonstrated significant efficacy in reducing obstructive sleep apnea (OSA) symptoms in adults with obesity, according to phase 3 clinical trial results published in The New England Journal of Medicine.
The SURMOUNT-OSA trial, which included 469 participants across multiple countries, showed that tirzepatide reduced the severity of moderate-to-severe OSA by nearly two-thirds in adults with obesity, potentially positioning it as the first pharmaceutical treatment for this condition.
Significant Reduction in Sleep Apnea Events
The international study examined two groups of participants with moderate-to-severe OSA and obesity: those unable or unwilling to use positive airway pressure (PAP) therapy (Study 1) and those who planned to continue using PAP therapy (Study 2). Participants received either tirzepatide or a placebo for 52 weeks.
Results were striking, with tirzepatide achieving all primary and key secondary endpoints. The medication produced a mean reduction of up to 62.8% on the apnea-hypopnea index (AHI), translating to approximately 30 fewer obstructive sleep apnea events restricting airflow per hour of sleep.
"It's estimated that up to 3 million people in the UK may have OSA but have not yet been diagnosed," said Dr. Kunal Gulati, Executive Director for Diabetes and Obesity Medical Affairs at Lilly Northern Europe. "Tirzepatide has the potential to be the first pharmaceutical treatment for OSA, which could address the unmet need for people living with this condition."
Disease Resolution in a Significant Percentage of Patients
Perhaps most promising was the finding that among participants receiving the highest dose of tirzepatide, 43% in Study 1 and 51.5% in Study 2 met the criteria for OSA "disease resolution." This suggests the medication could potentially eliminate the condition entirely for some patients.
At the start of the first trial, patients experienced an average of 51.5 apnea or hypopnea events per hour. Those given tirzepatide experienced on average 25.3 fewer such events per hour at 52 weeks, while those given a placebo had an average reduction of just 5.3 events per hour. Similar results were observed in the second trial.
The Obesity-Sleep Apnea Connection
Obstructive sleep apnea affects approximately 40 million people in the United States alone, with an estimated 70% of OSA patients also living with obesity. The condition occurs when the upper airway narrows or collapses during sleep, causing breathing to stop and start repeatedly.
"Obstructive sleep apnea is a sleep-related condition that results in the blockage or collapse of the upper airway, causing the sufferer to stop breathing several times a night," explained Dr. Monique May, a board-certified family physician for Aeroflow Sleep, who was not involved in the clinical trial. "The obstruction can be caused by a thick tongue, a thick neck, or excess fatty tissue in the upper airway, all of which are more common in [people with obesity]."
The health consequences of untreated OSA are significant. Dr. Seth Kipnis, Medical Director of Bariatric and Robotic Surgery at Hackensack Meridian Jersey Shore University Medical Center, noted: "Low oxygen levels while sleeping causes many diseases and sudden life-threatening events. These include heart disease, heart attacks, strokes, high blood pressure, and daytime fatigue."
Weight Loss as the Mechanism
Experts believe tirzepatide's effectiveness in treating OSA is primarily due to its weight loss effects rather than a direct impact on the sleep disorder itself.
"It's not directly from the medication, but a secondary effect of losing weight," explained Dr. Mir Ali, bariatric surgeon and Medical Director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center. "Any form of weight loss improves obstructive sleep apnea."
A spokesperson for Lilly elaborated: "In addition to reduction in body weight, we believe that reduction in tongue, airway and visceral ectopic fat deposits may have an additional beneficial effect in people living with OSA and obesity."
Broader Health Benefits
Beyond improvements in OSA symptoms, participants given tirzepatide also experienced significant weight loss, improvements in systolic blood pressure, and reported better sleep-related outcomes.
Professor Naveed Sattar, an expert in metabolic health at the University of Glasgow, called the results "really exciting" and suggested they "could revolutionize sleep apnea care in people living with obesity." He noted that weight loss would offer patients many other benefits that current treatments such as CPAP do not provide.
Current Treatment Landscape
Currently, the primary treatment for OSA is continuous positive airway pressure (CPAP) therapy, which requires patients to wear a mask connected to a machine that pumps air into the airway during sleep. While effective, many patients find CPAP therapy uncomfortable or difficult to use consistently.
Surgical options exist but are invasive and not suitable for all patients. The potential for a pharmaceutical treatment represents a significant advancement in OSA management.
Looking Forward to Broader Access
Despite the promising results, access to tirzepatide remains a challenge for many patients. Dr. Kipnis highlighted this issue: "By not covering or restricting access to effective weight reduction strategies, we have a population that is suffering. Currently, Medicare does not cover these drugs. Overall healthcare spending on an individual would drastically drop if obesity was prevented or treated."
As with any medication, tirzepatide is not without side effects. The most commonly reported adverse events were mild to moderate gastrointestinal issues, consistent with the known safety profile of the drug.
The study authors acknowledge that further research is needed to fully understand the long-term benefits and optimal use of tirzepatide for OSA treatment. Dr. Sanjay Patel of the University of Pittsburgh noted in an accompanying editorial that additional metrics would be necessary "to fully understand the magnitude of clinical benefit and allow comparisons with existing therapies for obstructive sleep apnea."
Nevertheless, these results represent a potentially transformative development in the treatment of a condition that affects millions worldwide and has historically been challenging to manage effectively.
