By: Asmaa Hassanin, PharmD Candidate c\/o 2026, Muskan Basra, PharmD Candidate c\/o 2027, Madelyn Lombardo, PharmD Candidate c\/o 2027, Aine Chen, PharmD Candidate c\/o 2028 <\/p>\n\n\n\n
Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterised by repeated episodes of partial (hypopnea) or complete (apnea) upper airway blockage while sleeping. These repeated episodes lead to abrupt decreases in oxygen saturation and frequent arousal from sleep to restore normal breathing.1<\/sup> OSA can impact quality of life by causing fragmented sleep, often marked by loud, frequent snoring, choking or gasping sounds upon airway opening, excessive daytime sleepiness, poor concentration, and an increased risk of cardiovascular and metabolic disorders.1 <\/sup>Obesity is a major risk factor for OSA, as excess body weight increases pressure on the airways, making them more susceptible to collapse. Fat deposits accumulate in the upper respiratory tract, particularly around the neck and throat, narrowing the airway.2 <\/sup>Additionally, obesity reduces lung volume, further compromising the ability to maintain an open airway.2 <\/sup>These combined factors contribute to the development and progression of OSA. <\/p>\n\n\n\n OSA affects almost 1 billion people globally, with 425 million adults between 30 to 69 having moderate-to-severe OSA.1<\/sup> The severity of OSA is classified using the Apnea- Hypopnea Index (AHI), which measures the number of apnea and hypopnea episodes per hour of sleep. Moderate OSA is defined by an AHI of 15-30 episodes per hour, while severe OSA is defined by an AHI of 30 or more episodes per hour.3<\/sup> <\/p>\n\n\n\n Currently, several treatment options are available for obese patients dealing with OSA, ranging from behavioural, dietary, and lifestyle modifications to surgical intervention. Obesity plays a significant role in the increased risk of developing OSA, and having<\/em> OSA can contribute to further weight gain, thus weight loss is a major treatment goal. Having a patient on a more conservative approach to treatment may look like addressing any underlying psychological conditions such as eating disorders, encouraging the patient to be active to combat living a sedentary lifestyle, having the patient on a reduced calorie diet, changing their sleeping position, and so on (2)(4)<\/sup>.In a ten-year sleep study known as the \u201cAHEAD Study\u201d, two groups followed two different conservative regimens, the Intensive Lifestyle Intervention (ILT) and the Diabetes Support and Education (DSE) in order to compare their long-term efficacy. Those in the ILT group demonstrated a higher probability of remission from OSA after 10 years of treatment, with ILT having a 34.4% remission rate compared to 22.2% in the DSE group. 9 <\/sup>A study titled \u201cImprovement in Obstructive Sleep Apnea With Weight Loss is Dependent on Body Position During Sleep\u201d observed that patients who still suffered OSA after weight loss benefited greatly by simply sleeping in a non-supine position, with 22% of these patients being able to resolve their OSA. Though these conservative strategies of targeting obesity and making lifestyle changes may have some beneficial outcomes in the short term, behavioural and dietary regimens have been found to be difficult to uphold in the long run, with only 10% of patients being effectively treated via one of these conservative methods. 9 <\/sup>The gold standard non-invasive therapy for OSA involves the use of continuous positive airway pressure, CPAP for short, which utilizes a continuous flow of air to the patient\u2019s airway via a nasal or oral appliance to maintain airway patency while asleep. CPAP treatment has been shown to improve the cardiometabolic changes and proinflammatory biomarkers associated with OSA and obesity, as well as improve symptoms such as daytime sleepiness, lowering of blood pressure, and overall improved quality of life. The only limitation to CPAP therapy is the fact that it can only be as efficacious as the patient\u2019s adherence. 6 <\/sup>There is speculation that CPAP may cause weight gain via a mechanism that is still unclear. A study conducted by Kyoto University demonstrated CPAP therapy significantly decreasing basal metabolic rate with no difference in physical activity, total caloric intake, and nutrition intake during the study. 6<\/sup> For patients intolerant to CPAP therapy or are unwilling to participate, the American Academy of Sleep Medicine (AASM) and American Academy of Dental Sleep Medicine (AADSM) suggest the use of custom made titratable mandibular repositioning oral appliances to curb snoring and reduce hypoxia. Though use of oral appliance therapy (OAT) is a viable option for patients with obesity, they are less likely to effectively respond to this kind of therapy, thus it is not recommended as a primary treatment option. 7<\/sup> The last alternative to the above treatment options would be various kinds of surgical interventions for those unaccepting of CPAP therapy or are at a particular BMI. The AASM recommends referral to a bariatric surgeon for obese patients with a BMI \u2265 35 kg\/m2<\/sup> who are intolerant or unwilling to undergo CPAP therapy. In December of 2024, Zepbound (tirzepatide) was approved as the first drug for OSA patients with obesity. The drug is used in combination with a reduced calorie diet and increased physical activity. 8<\/sup> <\/p>\n\n\n\n Tirzepatide is a synthetic polypeptide drug that acts as a dual GLP-1 and GIP agonist, which helps reduce high blood sugar levels and promotes weight loss. The drug enhances glycemic control by improving insulin secretion and sensitivity, suppresses glucagon secretion, and slows gastric emptying. For weight loss, tirzepatide reduces appetite by increasing feelings of satiety, contributing to significant body weight reduction at up to 22.4% over 72 weeks. It is mainly bound to plasma albumin, which allows it to remain in the bloodstream for a longer time. It is well-absorbed, with about 80% bioavailability, reaches its peak level within 8 to 72 hours after injection, and has a half-life of 5 days, allowing for weekly dosing. Tirzepatide is FDA-approved for type 2 diabetes mellitus and is also used off-label for obestiy.11<\/sup> <\/p>\n\n\n\n In a study conducted by the New England Journal of Medicine<\/em>, tirzepatide as evaluated for its potential use in treating OSA and obesity, two conditions that often occur together and are associated with significant cardiovascular risks. Overall, it was seen that tirzepatide improved symptoms associated with OSA, such as reduced hypoxic burden, while also contributing to significant weight loss in patients. These findings suggest that tirzepatide, in addition to its primary indication for treating type 2 diabetes, offers a promising off-label treatment for obesity and obstructive sleep apnea. By targeting both excess weight and the underlying metabolic dysfunctions that exacerbate OSA, tirzepatide may provide a holistic treatment option that goes beyond traditional mechanical treatments like CPAP, which is often difficult for patients to adhere to. In this experiment, most of the adverse effects were mild to moderate, with gastrointestinal issues being the most common.12<\/sup> <\/p>\n\n\n\n \u201cAdverse Events Related to Tirzepatide\u201d by Mishra et al., published in the Journal of the Endocrine Society<\/em>, presents a systematic review and meta-analysis of clinical trials evaluating the safety profile of tirzepatide. This systematic review assessed data from 10 clinical trials involving 6,836 participants to evaluate the rates of individual AEs across three doses of tirzepatide. The study found gastrointestinal (GI) AEs, particularly nausea and diarrhea, to be the most common and dose-dependent, with higher incidences observed at 10 mg and 15 mg doses. The analysis also stated that the incidence of serious AEs like severe hypoglycemia and pancreatitis remained low across all doses. Overall, the review provides important insights into the safety profile of tirzepatide.13<\/sup> <\/p>\n\n\n\n The impact of tirzepatide on moderate-to-severe OSA in adults with obesity was evaluated through two Phase 3, double-blind, randomized, controlled trials: SURMOUNT-OSA 1 and SURMOUNT-OSA 2. In SURMOUNT-OSA 1, participants who were not using positive airway pressure (PAP) therapy at baseline were enrolled, while SURMOUNT-OSA 2 included individuals who were already on PAP therapy for at least three consecutive months before screening and planned to continue its use. Participants were randomly assigned in a 1:1 ratio to receive either tirzepatide (10 mg or 15 mg, based on maximum tolerated dose) or a placebo for 52 weeks.14<\/sup> The study population included adults diagnosed with moderate-to-severe OSA (AHI \u226515 events per hour) and obesity (BMI \u226530 kg\/m\u00b2), but without type 1 or type 2 diabetes. 15 <\/sup>SURMOUNT-OSA 1 included 234 participants who were unable or unwilling to use PAP therapy. To qualify, the participants must not have used PAP for at least four weeks before screening. SURMOUNT-OSA 2, on the other hand, included 235 participants who had been on PAP therapy for at least three months prior to screening and planned to continue its use throughout the study. 15<\/sup> <\/p>\n\n\n\n The primary endpoint in both trials was the change in the apnea-hypopnea index (AHI) from baseline. At the start of the study, the mean AHI was 51.5 events per hour in Trial 1 and 49.5 events per hour in Trial 2, with an average BMI of 39.1 and 38.7, respectively. 15 <\/sup>After 52 weeks of treatment, participants in Trial 1 who were not using PAP therapy and received tirzepatide experienced an improvement in their sleep apnea, with an average AHI reduction of 25.3 events per hour, compared to a 5.3 events per hour reduction in the placebo group.15 <\/sup>Similarly, in Trial 2, participants treated with tirzepatide who were already on PAP therapy showed an average reduction of 29.3 events per hour, compared to 5.5 events per hour in the placebo group. 15 <\/sup>These results demonstrate that tirzepatide significantly reduced the severity of OSA in adults with obesity, regardless of PAP therapy, supporting its use a meaningful intervention for this high-risk population. <\/p>\n\n\n\n Tirzepatide represents a promising adjunctive treatment for OSA by targeting the metabolic and weight-related contributors to the disorder, potentially improving symptoms in patients with obesity-driven OSA. Unlike current traditional interventions such as CPAP that primarily address the mechanical aspects of OSA, tirzepatide treats OSA and improve symptoms by targeting the underlying pathophysiology through its weight reducing effect. This makes it a valuable option for patients who have not achieved adequate symptom control with conventional therapies. <\/p>\n\n\n\n While tirzepatide offers a novel therapeutic option, it requires close monitoring. It is contraindicated in individuals with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and should be used cautiously in those with a history of pancreatitis.16 <\/sup>Common side effects include gastrointestinal symptoms such as nausea, vomiting, and diarrhea, which may lead to dehydration and renal impairment in severe cases. There is also an increased risk of gallbladder complications, including gallstones and cholecystitis. To minimize adverse effects, a gradual dose escalation is recommended, along with regular monitoring of glucose levels, heart rate, and kidney function. 16<\/sup> <\/p>\n\n\n\n As the first approved medication for OSA, tirzepatide not only expands current treatment options but also shifts the focus toward addressing the root causes of the disease. Its long-term impact remains to be seen, but it holds great potential in improving quality of life and clinical outcomes for patients living with OSA. <\/p>\n\n\n\n References:<\/strong><\/p>\n\n\n\n By: Asmaa Hassanin, PharmD Candidate c\/o 2026, Muskan Basra, PharmD Candidate c\/o 2027, Madelyn Lombardo, PharmD Candidate c\/o 2027, Aine Chen, PharmD Candidate c\/o 2028 Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterised by repeated episodes of partial (hypopnea) or complete (apnea) upper airway blockage while sleeping. These repeated episodes lead to abrupt…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7,4],"tags":[],"class_list":["post-4197","post","type-post","status-publish","format-standard","hentry","category-clinical","category-featured"],"views":160,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/4197","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=4197"}],"version-history":[{"count":1,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/4197\/revisions"}],"predecessor-version":[{"id":4198,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/4197\/revisions\/4198"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=4197"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=4197"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=4197"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}\n