Sleep Apnea
Lauren Howell, PharmD
Results from a June 21, 2024, NEJM NEJMstudy suggest that tirzepatide may be a potential treatment for the more than 900 million people worldwide affected by sleep apnea. With current regimens ranging from nightly use of positive airway pressure (PAP) therapy and mandibular advancement therapy to upper airway surgery, tirzepatide could be the first effective pharmaceutical intervention for managing sleep apnea.
Obstructive sleep apnea is characterized by the repetitive collapse of the pharynx which causes the temporary cessation of breathing and an abnormally low respiratory rate. This results in decreased amounts of oxygen in the blood. As a consequence, patients can experience excessive drowsiness during the day and have an increased risk of injury, including being prone to motor vehicle accidents and work-related injuries. Sleep apnea has also been identified as an independent risk factor for CVD.
While PAP has been shown to improve the apnea-hypopnea index (AHI)—the number of apneas and hypopneas during an hour of sleep—trials have failed to indicate that it reduces adverse cardiovascular outcomes or death. Additionally, some patients are unable or unwilling to use PAP therapy. For these patients, an injectable medication could be the key to reducing symptoms and improving quality of life.
Study design
The study consisted of two 52-week, phase 3, multicenter, parallel-group, double-blind, randomized controlled trials that were conducted at 60 sites across nine countries to evaluate both the efficacy and safety of 10 mg or 15 mg of tirzepatide in adults with moderate-to-severe obstructive sleep apnea and obesity. Trial 1 included participants who were either unable or unwilling to use PAP therapy and trial 2 included participants who had been using PAP therapy for at least 3 months.
Participants were assigned to either trial, based on PAP therapy use, and randomly assigned to receive tirzepatide or placebo subcutaneously once weekly using a single-dose pen autoinjector. All participants also received lifestyle counseling and adhered to a 500 kilocalorie per day deficit and at least 150 minutes of physical activity per week. Participants receiving tirzepatide were given an initial dose of 2.5 mg once weekly and increased the dose by 2.5 mg every 4 weeks until the maximum tolerated dose of 10 mg or 15 mg was reached. The primary endpoint was the change in AHI from baseline.
Results
In trial 1 with participants who did not use PAP therapy, the tirzepatide group had a change in AHI of –27.4 events per hour and the placebo group had a change in AHI of –4.8 events per hour at week 52. The estimated treatment difference was –22.5 events per hour.
In trial 2 with participants who did use PAP therapy, the change in AHI at week 52 with tirzepatide was –30.4 events per hour and –6.0 events per hour with placebo. The estimated treatment difference was –24.4 events per hour. Both participants who used PAP therapy and those who did not had significant reductions in AHI and the sleep apnea–specific hypoxic burden at week 52 of receiving tirzepatide.
AHI changes seen with tirzepatide use were clinically relevant based on the American Academy of Sleep definition for the clinical significance threshold for AHI as 15 or more events per hour. A meaningful number of participants who received tirzepatide also met the secondary endpoint criteria of fewer than 5 AHI events per hour or 5 to 14 AHI events per hour with a score of 10 or less on the Epworth Sleepiness Scale. Individuals who meet these thresholds for disease severity may not require PAP therapy, indicating that tirzepatide could potentially allow some patients to stop using PAP therapy on a nightly basis.
Malhotra and colleagues wrote that while these findings are generalizable, potential weaknesses of the study are that long-term cardiovascular outcomes were not assessed and individuals without obesity were excluded. More research is recommended to investigate a period of treatment with tirzepatide of longer than 52 weeks in the future. ■