Reference photo: Unsplash
GLP-1 Indications
Glucagon-like peptide (GLP-1) medications were first approved by FDA in 2005 for type 2 diabetes. In the treatment of type 2 diabetes, GLP-1s work by stimulating insulin secretion from the pancreas to lower glucose levels. Since then, these medications have had many additional indications. Some of those indications include cardiovascular, weight management, and chronic kidney disease (CKD).
On December 20, 2024, the U.S. Food and Drug Administration added another indication to that list. Zepbound (tirzepatide) was initially FDA approved in 2023 to treat adults with obesity or those who are overweight who have weight-related medical issues. Later, tirzepatide was approved for the treatment of moderate to severe obstructive sleep apnea (OSA) in adults with obesity. Tirzepatide (Zepbound) works on agonism of GLP-1 receptors and glucose dependent insulinotropic polypeptide (GIP) receptors. The duality of this medication is multi-faceted and is making great strides for patients with OSA.
Obstructive Sleep Apnea and Zepbound’s Role
So, what is obstructive sleep apnea (OSA)? Obstructive sleep apnea is a very serious sleep disorder that involves one’s airway to become repeatedly blocked during sleep, causing the person to stop breathing briefly and oxygen deprivation. This is typically caused by the closing of the throat tissue, leading to choking noises, loud snoring, gasping for air during sleep, and frequent awakening. Now, OSA can affect anyone, but is it more likely to affect those who are overweight or obese.
Continuous airway positive pressure (CPAP) is considered to be the gold standard of therapy for the treatment of OSA. A CPAP machine uses a hose connected to a mask or nose piece that delivers constant air while one sleeps. A comprehensive systematic literature review was conducted in 2016 using reliable databases searching for data regarding CPAP adherence. The research revealed that over a 20-year period, 1994-2015, a CPAP non-adherence rate of 34.1% occured when assuming a sleep duration of 7 hours per night. This rate showed no significant improvement throughout the studied timeframe. Even after behavioral intervention, adherence only improved by about 1 hour per night on average.
Reference photo: Unsplash
So where does Zepbound come to aid in the treatment of OSA? Zepbound functions by suppressing appetite and decreasing food consumption. Research indicates that by promoting weight loss, Zepbound can also lead to improvements in obstructive sleep apnea. Zepbound is also approved for use alongside a reduced-calorie diet and increased physical activity to help adults with obesity. Zepbound is also indicated for those who are overweight with at least one weight-related health condition and this can help patients lose excess weight and maintain long-term weight reduction.
FDA Approval
The FDA approval for using Zepbound came from the SURMOUNT-OSA Phase 3 clinical trials. This study randomized 469 participants, where two Phase 3, double-blind controlled trials were conducted in adults with moderate-to-severe obstructive sleep apnea and obesity. Trial 1 included participants who were not on positive airway pressure (PAP) therapy at the start, while Trial 2 included those already using PAP therapy. Participants were randomly assigned in a 1:1 ratio to receive either a placebo or their maximum tolerated dose of tirzepatide (10 mg or 15 mg) for a duration of 52 weeks.
Reference photo: Unsplash
After one year of treatment, Zepbound led to a reduction in breathing interruptions by 25 to 29 events per hour, compared to a 5 to 6 event reduction with placebo. Remission or transition to mild sleep apnea was observed in 42% of participants not using PAP therapy and 50% of those using PAP (versus 16% and 14%) respectively, in the placebo groups.
Participants treated with Zepbound also experienced substantial weight loss, averaging 18–20% of their body weight (approximately 45–50 pounds), while those receiving placebo lost only about 2% (roughly 4–6 pounds). The weight reduction was more pronounced in individuals using PAP therapy. The improvement in the Apnea- Hypopnea Index (AHI), a key measure used to diagnose and assess the severity of OSA, in participants with OSA is more than likely related to body weight reduction with Zepbound.
The Bottom Line
Like any other GLP-1 medication, the side effects remain the same with the most reported being nausea, vomiting, and diarrhea. Other side effects include constipation, abdominal (stomach) discomfort and pain, injection site reaction, fatigue, and more. Additionally, if Zepbound is taken alongside insulin or medications that increase insulin production, it’s important to discuss with a healthcare provider whether adjustments to those medications are needed to help lower the risk of hypoglycemia (low blood sugar). Health care providers should routinely monitor weight, kidney function, complete blood count, and blood glucose levels. Dieticians also need to make recommendation for patients to consume smaller meals, eating slowly, and avoiding fatty foods while taking these medications so the patient can continue to achieve maximum treatment benefit.
Zepbound (tirzepatide) represents a significant advancement in the management of obstructive sleep apnea (OSA), particularly for individuals with obesity. With longstanding challenges in CPAP adherence and the strong link between excess weight and OSA severity, the introduction of a medication that addresses both issues offers a promising new approach. The SURMOUNT-OSA Phase 3 trials demonstrated meaningful reductions in apnea events and body weight, highlighting Zepbound’s dual benefit in both sleep and metabolic health. While side effects are consistent with those seen in other GLP-1 therapies, the potential improvements in quality of life and disease burden make this an important new option for appropriate patients. As with any treatment, shared decision-making between patients and healthcare providers will be essential in weighing risks, benefits, and individual goals.
Grace N., APPE Student
References:
CPAP machines: Tips for avoiding 10 common problems. https://www.mayoclinic.org/diseases-conditions/sleep-apnea/in-depth/cpap/art-20044164#:~:text=Continuous%20positive%20airway%20pressure%20(CPAP,you%20breathe%20while%20you%20sleep. Accessed: June 5, 2025.
FDA Approves First Medication for Obstructive Sleep Apnea. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea. Accessed: June 4, 2025.
Latif, W., Lambrinos, K. J., & Rodriguez, R. (2021). Compare and contrast the glucagon-like peptide-1 receptor agonists (GLP1RAs).
Malhotra, Atul, et al. “Tirzepatide for the treatment of obstructive sleep apnea and obesity.” New England Journal of Medicine 391.13 (2024): 1193-1205.
Romariz, Livia, et al. “GLP-1 receptor agonists for the treatment of obstructive sleep apnea and obesity.” European Journal of Internal Medicine 132 (2025): 153-155. Accessed June 4, 2025.
Rotenberg, B. W., Murariu, D., & Pang, K. P. (2016). Trends in CPAP adherence over twenty years of data collection: a flattened curve. Journal of Otolaryngology-Head & Neck Surgery, 45(1), 43. Accessed: June 5, 2025
Zepbound approved by FDA as first sleep apnea medication. https://aasm.org/zepbound-approved-fda-first-sleep-apnea-medication/. Accessed June 4, 2025.
Zepbound Approved for Obstructive Sleep Apnea in Patients With Obesity. https://www.pulmonologyadvisor.com/news/zepbound-approved-for-obstructive-sleep-apnea-in-patients-with-obesity/#:~:text=%E2%80%9CNearly%20half%20of%20clinical%20trial,1%20weight%2Drelated%20comorbid%20condition.&text=References:,us/zepbound%2Duspi.pdf. Accessed: June 5, 2025.