Tirzepatide: A Novel Approach in Obstructive Sleep Apnea Management


Obstructive sleep apnea (OSA) is a significant public health concern, with a high prevalence worldwide, especially in developed countries. Studies such as the Wisconsin Sleep Cohort have reported that 17.4% of women and 33.9% of men in the United States aged 30 to 70 years suffer from at least mild OSA, defined by an apnea-hypopnea index (AHI) of 5 to 14.9 events per hour of sleep. Furthermore, 5.6% of women and 13.0% of men experience moderate (AHI of 15-29.9 events per hour) or severe (AHI ≥30 events per hour) OSA. The prevalence of OSA is on the rise due to the global obesity epidemic and an aging population. Obesity, a major risk factor for OSA, contributes to this increase through mechanisms that are not entirely understood but may include increased fat deposits in the tongue and surrounding airway tissues.

The Role of Weight Reduction in OSA Management

Weight loss has been recognized as a beneficial intervention for patients with OSA. Reducing body weight, particularly the adipose tissue around the upper airways and abdomen, can lead to improvements in OSA severity by decreasing the frequency of respiratory events and the degree of oxygen desaturation. Moreover, weight loss can positively impact cardiometabolic risk markers such as high-sensitivity C-reactive protein (hsCRP), blood pressure, and insulin resistance. It also enhances patient-reported outcomes (PROs) including quality of life, fatigue, sleepiness, energy levels, depression, and overall well-being.

Advances in Pharmacotherapy: Tirzepatide

Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promise in managing obesity and type 2 diabetes. This medication has demonstrated significant efficacy in controlling carbohydrate and lipid metabolism and reducing body weight. The SURMOUNT-1 and SURMOUNT-2 studies highlighted mean weight reductions of up to 22.5% and 15.7% in participants without and with type 2 diabetes, respectively. Despite its approval by the US Food and Drug Administration (FDA) for glycemic control in adults with type 2 diabetes and as an adjunct for chronic weight management, its potential role in managing OSA among individuals with obesity remains unexplored.


The SURMOUNT-OSA trial is designed to investigate the efficacy of tirzepatide in treating OSA among participants with obesity. The study aims to determine whether tirzepatide can yield clinically meaningful improvements in OSA severity, as measured by the AHI. Additionally, the trial will evaluate various PROs relevant to the disease burden and other clinically significant outcomes to provide a comprehensive understanding of tirzepatide’s impact.

Current OSA Management Strategies

Current management of OSA primarily focuses on treating symptoms rather than addressing the underlying disease. Positive airway pressure (PAP) therapy is the first-line treatment, providing substantial benefits to many patients. However, adherence to PAP therapy is variable, with some patients finding it burdensome. Alternative treatments, such as mandibular advancement devices or hypoglossal nerve stimulation, have limited clinical evidence supporting their efficacy. Thus, there is a pressing need for alternative and more effective treatment options.

Study Design and Objectives

SURMOUNT-OSA is meticulously designed to evaluate the efficacy and safety of tirzepatide in participants with OSA and obesity. The study will measure the treatment’s effect on sleep-disordered breathing directly through changes in AHI, responder rate analysis, hypoxic burden, objective sleep patterns, and various PROs. Furthermore, it will assess the impact of tirzepatide on cardiometabolic indicators such as blood pressure, lipids, fasting insulin, and inflammation markers like hsCRP.

The trial will include two standalone interventional sub-analyses (ISAs) to evaluate tirzepatide’s effectiveness in participants with and without PAP therapy. This approach aims to maximize the generalizability of the findings in OSA management. For participants not using PAP therapy (ISA-1), tirzepatide is expected to provide weight reduction and improve body composition, leading to better cardiovascular risk markers. Similar benefits are anticipated for participants using PAP therapy (ISA-2), considering the tendency for weight gain associated with PAP therapy.

Gender Representation and Post-Hoc Analysis

To ensure a representative sample, the study has capped male enrollment at 70%, addressing the need to understand the disease dynamics in both sexes. This is crucial as the onset, pathophysiologic mechanisms, and symptomatology of OSA may differ between males and females. Adequate representation will allow for multiple post-hoc analyses, providing deeper insights into these differences.

Patient-Reported Outcomes

In addition to objective outcomes, the SURMOUNT-OSA trial will thoroughly assess well-validated PROs to evaluate tirzepatide’s impact on participants’ overall well-being. The PROs will be measured using instruments such as the FOSQ-10, FOSQ-30 vigilance, and FOSQ-30 activity level subscales, the Patient-Reported Outcomes Measurement Information System sleep-related impairment and sleep disturbance forms, and the Epworth Sleepiness Scale.

Potential Limitations of the Study

While the SURMOUNT-OSA study is robust in its design, several potential limitations exist. The study is powered to assess the efficacy of tirzepatide on sleep-disordered breathing and selected cardiometabolic risk factors but not on cardiovascular outcomes such as mortality, stroke, or myocardial infarction. Thus, the findings may serve as a rationale for subsequent large-scale studies. Additionally, while the study design allows for mediation analyses, it may not definitively determine whether improvements are due to weight loss or the resolution of OSA per se. Changes in CPAP adherence, residual AHI, and mask leak could also confound the results. Another limitation is the potential for unblinding if significant weight loss occurs in the tirzepatide arm, which could influence subjective reported outcomes. However, these improvements are expected to be genuine rather than theoretical concerns. Lastly, the study evaluates a 52-week treatment period, and there is a need for long-term strategies to maintain weight loss and prevent OSA complications, considering potential issues with medication adherence due to costs, accessibility, side effects, and perceived convenience.


The SURMOUNT-OSA study is set to provide critical insights into the potential role of tirzepatide in managing obesity-related OSA by addressing an underlying cause rather than just symptoms. The study’s comprehensive design, including objective and subjective outcome measures, aims to guide optimal OSA management strategies, emphasizing the importance of weight management. It will also explore whether tirzepatide’s benefits stem primarily from BMI reduction or other factors such as improvements in upper airway fat, loop gain, insulin resistance, or inflammation. The use of advanced technology like HSAT/actigraphy and MRI addendums will enhance the understanding of tirzepatide’s effects on sleep and airway anatomy, potentially paving the way for innovative OSA treatments.

This trial represents a significant step forward in the pursuit of effective, holistic, and sustainable management options for OSA, particularly for those grappling with obesity. By expanding on the current knowledge and addressing the limitations of existing therapies, SURMOUNT-OSA holds the promise of improving the lives of many individuals suffering from this prevalent and impactful disorder.

reference link : https://www.sciencedirect.com/science/article/pii/S1551714424000995?via%3Dihub#s0060


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