New drug tirzepatide significantly improves sleep apnea and weight loss

In a recently published study, New England Journal of Medicine, Researchers investigated the effects of tirzepatide in adults with obesity and moderate to severe obstructive sleep apnea (OSA).

The researchers found that compared with placebo, tirzepatide significantly reduced apnea-hypopnea index (AHI), weight, high-sensitivity C-reactive protein (hsCRP) concentrations, hypoxia load, and systolic blood pressure (SBP), and improved patient-reported sleep-related outcomes.

study: Tirzepatide for the treatment of obstructive sleep apnea and obesityImage courtesy of: WESTOCK PRODUCTIONS/Shutterstock.com

background

OSA is characterised by repeated pharyngeal collapse during sleep, resulting in apnea, hypopnea, hypoxemia, hypercapnia and awakenings, with significant symptoms including excessive daytime sleepiness and increased risk of cardiovascular disease. With over 900 million people affected worldwide, 40% of whom experience moderate to severe OSA, the disease has a major medical and economic impact.

Traditional treatment of this disease focuses on mechanical support, primarily positive airway pressure (PAP) therapy, which improves AHI but has limited adherence and no proven reduction in cardiovascular outcomes.

Alternative treatments, such as mandibular advancement and upper airway surgery, are less effective or more invasive. Additionally, there are no approved medications for OSA.

Excess fat is a significant reversible risk factor, making weight management crucial. Tirzepatide, a long-acting GIP (short for glucose-dependent insulinotropic polypeptide) and GLP-1 (short for glucagon-like peptide-1) receptor agonist, has been shown to significantly reduce weight, blood pressure, and inflammation, suggesting that addressing obesity and its associated complications may have an effect on OSA.

In this study, researchers present results from two phase 3 safety and efficacy trials of SURMOUNT-OSA. Efficacy Tirzepatide in the treatment of adults with OSA and obesity.

About the Research

The SURMOUNT-OSA trials consist of two Phase III, double-blind, randomized controlled trials conducted at 60 sites in nine countries between June 2022 and March 2024, and are designed to evaluate the safety and efficacy of tirzepatide in adults with moderate to severe OSA (AHI ≥ 15 beats per hour) and obesity (BMI ≥ 30; ≥ 27 in Japan).

Study 1 included participants who were unable or unwilling to use PAP therapy, and Study 2 included participants who had been using PAP therapy for at least 3 months. Participants were excluded if they had type 1 or type 2 diabetes, had recently experienced significant weight change, were scheduled for surgery for sleep apnea or bariatric surgery, had significant craniofacial abnormalities, or had central or mixed sleep apnea.

The mean age of participants was 47.9 and 51.7 years in Studies 1 and 2, respectively. The majority of participants were male (67.1%, 72.3%) and Caucasian (65.8%, 73.1%).

After a 4-week screening, participants were assigned to Study 1 (n = 234) or Study 2 (n = 235) and randomly received tirzepatide or placebo once weekly for 52 weeks.

The primary outcome was the change in AHI from baseline.Secondary outcomes included percentage change in AHI, ≥50% reduction in AHI, achievement of ≥5 AHI per hour, change in weight, hsCRP concentration, hypoxemia, PROMIS (short for Patient-Reported Outcomes Measurement Information System) scores for sleep disturbance (PROMIS-SD) and sleep-related disorders (SRI), and SBP.

Adverse events and serious adverse events were monitored throughout the reporting period.Statistical analyses included treatment schedule and efficacy estimates, analysis of covariance, logistic regression, and multiple imputation of missing data.

Results and discussion

The trials showed high completion rates (82.9%) and high overall adherence (79.7%).Estimand analysis showed that in both trials, tirzepatide treatment resulted in a significant reduction in AHI compared with placebo (p<0.001).

Additionally, participants taking tirzepatide experienced improvements in sleep apnea-specific hypoxic load, with more than 50% achieving a clinically meaningful reduction in AHI.

Additionally, participants who received tirzepatide in both studies 1 and 2 experienced significant reductions in PROMIS-SRI and PROMIS-SD T-scores, body weight, systolic blood pressure, and hsCRP concentrations.

No deaths were reported during the trials. However, participants receiving tirzepatide had a higher incidence of gastrointestinal adverse events, including two cases of acute pancreatitis in study 2.

These trials were strengthened in that they were conducted worldwide, were sufficiently large, included a large number of women, assessed multiple relevant endpoints, and were generalizable, providing insight into the efficacy of tirzepatide in patients who were and were not currently receiving PAP therapy.

However, limitations of the study include the short duration, exclusion of non-obese participants, lack of analysis of PAP adherence, failure to examine the presence of symptoms at baseline, failure to define the clinical importance of PROMIS measures, and assessment of treatment duration up to 52 weeks only.

Conclusion

In conclusion, in two studies, tirzepatide was found to produce clinically significant improvements in sleep-disordered breathing, sleep disturbances, and sleep-related disorders in patients with moderate to severe OSA and obesity, while simultaneously reducing OSA-related cardiovascular risk factors, including AHI, body weight, hypoxemia, hsCRP concentration, and SBP.

These results highlight the potential of tirzepatide as a treatment option to improve sleep-related outcomes in this population.