1. In this randomized controlled trial, in patients with both moderate-severe obstructive sleep apnea (OSA) and obesity, it was found that tirzepatide treatment reduced the occurrence of apneas and hypopneas.

2. Tirzepatide treatment was associated with reduced body weight and sleep apnea-associated cardiovascular risk factors.

Evidence Rating Level: 1 (Excellent)

Study Rundown: OSA, resulting from nocturnal pharyngeal collapse, is associated with significant morbidity, including daytime fatigue, elevated blood pressure, and cardiovascular complications. While positive airway pressure (PAP) therapy is commonly prescribed to alleviate these symptoms, poor adherence has limited its effectiveness for many patients. It is well-established that managing obesity can mitigate the effects of sleep apnea. Tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce body weight and improve cardiovascular health. This study aimed to evaluate the safety and efficacy of tirzepatide in treating OSA through two separate trials: one involving participants not using PAP (Trial 1) and another involving PAP users (Trial 2). Results from both trials indicated that tirzepatide treatment led to a clinically significant reduction in the apnea-hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep). Additionally, tirzepatide reduced body weight, sleep apnea-specific hypoxic burden, systolic blood pressure, high-sensitivity C-reactive protein (hsCRP) levels, and perceived sleep disturbances. However, the study had several limitations: it excluded participants without obesity, did not investigate whether tirzepatide influences PAP adherence, did not examine potential variations in results based on baseline symptoms, and did not assess long-term cardiovascular outcomes. Despite these limitations, the findings suggest that tirzepatide may be an effective treatment for OSA, potentially alleviating many of its associated symptoms.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: This study involved two randomized controlled trials that investigated the safety and efficacy of tirzepatide for treating OSA and obesity. Adults with moderate-to-severe OSA (AHI ≥15 events per hour) and obesity (BMI ≥30 or BMI ≥27 for Japanese participants) were included. Participants were eligible for Trial 1 if they were either unable or unwilling to use PAP therapy, while Trial 2 included those using PAP who could continue this therapy throughout the study. Exclusion criteria included a diagnosis of type 1 or type 2 diabetes mellitus, a weight change greater than 5 kg in the three months before screening, planned surgery for sleep apnea or obesity, central or mixed sleep apnea, or facial structural abnormalities. A total of 469 participants were enrolled in the study: 234 in Trial 1 (114 assigned to tirzepatide and 120 to placebo) and 235 in Trial 2 (120 assigned to tirzepatide and 115 to placebo). The primary outcome was the change in AHI from baseline. In Trial 1, the tirzepatide group experienced a reduction in AHI of 25.3 events per hour (95% Confidence Interval [CI], -29.3 to -21.2), while the placebo group showed a decrease of 5.3 events per hour (95% CI, -9.4 to -1.1), yielding an estimated treatment difference of -20.0 events per hour (95% CI, -25.8 to -14.2; p<0.001). In Trial 2, the tirzepatide group saw a reduction of 29.3 events per hour (95% CI, -33.2 to -25.4), compared to a reduction of 5.5 events per hour in the placebo group (95% CI, -9.9 to -1.2), with an estimated treatment difference of -23.8 events per hour (95% CI, -29.6 to -17.9; p<0.001). Additionally, tirzepatide-treated participants reported lower sleep impairment (95% CI, -5.7 to -2.2; p<0.001) and fewer sleep disturbances (95% CI, -4.5 to -1.5; p<0.001) compared to placebo. These findings suggest that tirzepatide may be an effective treatment for OSA and obesity.

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