The New England Journal of MedicineTirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity

Tirzepatide shows potential in reducing the severity of obstructive sleep apnea and related obesity metrics, offering valuable insights into the interplay between sleep disorders and metabolic health.

This study evaluates the efficacy of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in treating adults with moderate-to-severe obstructive sleep apnea (OSA) and obesity. Conducted over 52 weeks, the trials assess the impact of tirzepatide on the apnea–hypopnea index (AHI), body weight, and other cardiovascular and metabolic parameters, providing practical insights for clinicians managing these intertwined conditions.

Study Design:

• Participants:
  • Adults with moderate-to-severe OSA and obesity.
  • Trial 1: Participants not on positive airway pressure (PAP) therapy at baseline.
  • Trial 2: Participants on PAP therapy at baseline.
• Duration: 52 weeks.
• Intervention: Maximum tolerated dose of tirzepatide (10 mg or 15 mg) versus placebo.
• Primary Endpoint: Change in apnea–hypopnea index (AHI) from baseline.
• Secondary Endpoints:
  • Percent change in AHI and body weight.
  • Changes in hypoxic burden.
  • Patient-reported sleep impairment and disturbance.
  • High-sensitivity C-reactive protein (hsCRP) concentration.
  • Systolic blood pressure.

Key Findings:

• Baseline Characteristics:
  • Mean AHI: 51.5 events/hour (trial 1) and 49.5 events/hour (trial 2).
  • Mean BMI: 39.1 (trial 1) and 38.7 (trial 2).
• Primary Endpoint:
  • Trial 1: Mean AHI reduction of 25.3 events/hour with tirzepatide vs. 5.3 events/hour with placebo.
  • Trial 2: Mean AHI reduction of 29.3 events/hour with tirzepatide vs. 5.5 events/hour with placebo.
  • Significant treatment differences in both trials (P<0.001).
• Secondary Endpoints:
  • Significant improvements in percent change in AHI and body weight.
  • Reductions in hypoxic burden.
  • Improvements in patient-reported sleep impairment and disturbance.
  • Decrease in hsCRP concentration.
  • Reduction in systolic blood pressure.
• Adverse Events:
  • Commonly gastrointestinal, mostly mild to moderate.

HCN Medical Memo
This study highlights the potential of tirzepatide as a multifaceted treatment option for patients with obstructive sleep apnea and obesity, emphasizing improvements in sleep quality, cardiovascular risk markers, and weight management. Clinicians should consider the broader metabolic benefits when evaluating treatment plans for these patients.

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