Tirzepatide Injection (Zepbound) for Obstructive Sleep Apnea
January 30, 2025
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration has approved tirzepatide for the treatment of moderate-to-severe sleep apnea in adults with obesity. Tirzepatide, a glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, is effective for treating type 2 diabetes under the brand name Mounjaro and reducing excess body weight and maintaining weight reduction as Zepbound. This new indication, under Zepbound, was given a priority review and accelerated approval with a fast-track breakthrough therapy designations.1
Indications
Tirzepatide is indicated to treat moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity.2 It is to be used in combination with a reduced-calorie diet and increased physical activity.
Dosage
The recommended starting dose is 2.5 mg given subcutaneously once weekly for four weeks.2 The dose is increased at 2.5 mg increments after at least four weeks until the recommended maintenance dose is achieved (10 mg or 15 mg once weekly).
Potential Advantages
Tirzepatide is the first pharmacological therapy for moderate-to-severe OSA in obese patients.
Potential Disadvantages
As with other GLP-1 agonists, tirzepatide carries a box warning for the risk of thyroid C-cell tumors and is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2.2 Suicidal behavior and ideation, acute pancreatitis, and pulmonary aspiration during general anesthesia or deep sedative have been reported. Most frequent (vs. placebo) adverse reactions include nausea (25% to 28% vs. 8%), diarrhea (19% to 23% vs. 8%), vomiting (8% to 13% vs. 2%), constipation (11% to 17% vs. 5%), increase in pancreatic amylase (20% to 25% vs. 2%), and increase in serum lipase (28% to 35% vs. 5.8%).2
Comments
The efficacy of tirzepatide was evaluated in two Phase III, double-blind, randomized controlled trials (SURMOUNT-OSA) in adult subjects with moderate-to-severe OSA, and body mass indexes (BMIs) ≥ 30.2,3 Those unwilling or unable to use treatment with positive airway pressure (PAP) at baseline were enrolled in Trial 1 and those receiving PAP were enrolled in Trial 2. Those with type 2 diabetes were excluded. Participants were assigned to a maximum tolerated dose of tirzepatide (10 mg or 15 mg) (n = 114 and 119) or placebo (n = 120 and 114) for 52 weeks. Participants received instructions on a reduced-calorie diet and increased physical activity. The primary efficacy endpoint was the change in the number of apneas and hypopneas during an hour of sleep (apnea-hypopnea index [AHI]) from baseline. Secondary endpoints included percent change in AHI from baseline, change in hypoxic burden, percent change in body weight, and patient-reported sleep impairment and disturbance.
At baseline, the mean age of participants was 50.7 (±11) years. About two-thirds had severe OSA, mean 51 (±31) AHI events/hour, mean total hypoxic burden 200.7% (±182)% min/hour, and mean BMI 39 kg/m2. Tirzepatide reduced AHI by 20 to 23.8 events/hour, percent change treatment difference of -48% to 56%, and 61 to 70 reduction (% min/hour) in sleep apnea-specific hypoxic burden relative to placebo. Forty-two percent to 50% achieved remission or mild non-symptomatic OSA compared to 14% to 16% for placebo. There also was a 16 kg to 17 kg weight reduction difference between treatment and placebo groups. Tirzepatide showed improvement in sleep-related impairment compared to placebo.
Clinical Implications
OSA is a common disorder where sleep is interrupted by abnormal breathing lasting for longer than 10 seconds at least five times an hour throughout the sleep period. Excess adiposity is a major reversible risk factor for OSA. The most common treatment for moderate-to-severe OSA is sleeping with a continuous positive airway pressure (CPAP) machine and mask. Pharyngeal surgery is a surgical option. In many patients, insomnia and OSA co-occur.5 These are associated with lower rates of PAP tolerance. Weight-loss interventions are associated with improvement in OSA severity.6 Tirzepatide, when used with reduced-calorie diet and increased physical activity, is effective for OSA in obese individuals using or not using CPAP. The improvement in OSA associated with tirzepatide likely is related to body weight loss.1 Tirzepatide as Zepbound costs $1,060 for a four-week supply.
References
- U.S. Food and Drug Administration. FDA approves first medication for obstructive sleep apnea. Published Dec. 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea
- Lilly USA. Zepbound prescribing information. Revised March 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217806s003lbl.pdf
- Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391:1193-1205.
- Johns Hopkins Medicine. Obstructive sleep apnea. https://www.hopkinsmedicine.org/health/conditions-and-diseases/obstructive-sleep-apnea
- Saber KM, Patil RD. Comorbid insomnia and sleep apnea: Challenges and treatments. Otolaryngol Clin N Am. 2024;57:385-393.
- Hudgel DW, Patel SR, Ahasic AM, et al. The role of weight management in the treatment of adult obstructive sleep apnea. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2018;198(6):e70-e87.
The U.S. Food and Drug Administration has approved tirzepatide for the treatment of moderate-to-severe sleep apnea in adults with obesity.
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