In adults with moderate-to-severe obstructive sleep apnoea (OSA) and obesity, tirzepatide significantly reduced the apnea-hypopnea index (AHI) and body weight compared to placebo, with notable improvements in sleep-related outcomes and cardiovascular risk factors, albeit with increased gastrointestinal side effects.
PICO Summary
• Population:
Adults with moderate-to-severe OSA and obesity (BMI ≥30), excluding those with diabetes, significant weight changes in the past three months, or central/mixed sleep apnoea. Trial 1 included those not on positive airway pressure (PAP), and Trial 2 included PAP users.
• Intervention:
Tirzepatide administered weekly, escalating to a maximum tolerated dose (10 mg or 15 mg) over 52 weeks.
• Comparison:
Placebo, administered weekly, with both groups receiving lifestyle counselling for calorie restriction and physical activity.
• Outcome:
• Efficacy: Significant reductions in AHI at week 52, with tirzepatide achieving reductions up to 58.7% versus 3% in the placebo group (P < 0.001). Weight loss and improvements in cardiovascular markers (e.g., hsCRP and blood pressure) were also observed.
• Safety and Tolerability: Gastrointestinal side effects (e.g., nausea, vomiting, diarrhoea) were common and dose-dependent, mostly mild to moderate.
Clinical Summary
• Main Finding:
Tirzepatide significantly reduced AHI and body weight in patients with moderate-to-severe OSA and obesity, achieving clinically relevant outcomes that suggest a reduced need for PAP in some patients. It also improved sleep quality, reduced hypoxic burden, and lowered blood pressure and inflammatory markers.
• Clinical Relevance:
This study supports tirzepatide as a promising alternative for OSA management, especially in patients struggling with PAP adherence or seeking non-mechanical interventions. Weight loss and reduced AHI align with reduced cardiovascular risks, suggesting tirzepatide could help manage the broader cardiometabolic implications of OSA.
Study Overview
• Type of Study:
Two-phase 3, double-blind, randomised controlled trials.
• Sample Size & Population:
469 adults with OSA and obesity across two trials, approximately 70% male.
• Intervention Duration & Doses:
52-week treatment with tirzepatide (dose-escalated weekly to 10 mg or 15 mg) or placebo, including 20 weeks of dose escalation.
• Comparison:
Placebo with a similar regimen of lifestyle modification counselling.
Outcomes
• Primary Measure (AHI):
Significant AHI reduction of up to 29.3 events/hour with tirzepatide versus 5.3 with placebo, demonstrating a clinically relevant change (P < 0.001).
• Secondary Measures (Weight and Cardiovascular Markers):
Weight reduction was significantly greater with tirzepatide (up to 19.6% decrease vs. 2.3% with placebo). Marked reductions in hsCRP, blood pressure, and PROMIS scores indicated improvement in both cardiovascular and quality-of-life parameters.
• Safety Profile:
Gastrointestinal events were the most reported side effects, with some participants discontinuing due to intolerability. There were also rare cases of severe adverse events, including acute pancreatitis.
Considerations:
The study’s duration does not capture long-term cardiovascular outcomes. Additionally, the high incidence of gastrointestinal side effects may limit the tolerability of tirzepatide in some patients. Future studies should evaluate the impact on longer-term health outcomes and alternative dosing strategies.
Reference:
Malhotra, A., et al. (2024). New England Journal of Medicine, 391(13), 1193-1205. DOI:10.1056/NEJMoa2404881
Disclosure:
This article on Hormone Insight was created with assistance from both humans and AI. The human expert editor reviewed the article before publication to ensure accuracy, quality, and clarity.
