Experimental Weight-Loss Drug Shows Promise in Treating Sleep Apnea

An experimental weight-loss drug, retatrutide, has demonstrated a significant reduction in symptoms associated with obstructive sleep apnea (OSA) in two clinical trials, according to research published in The New England Journal of Medicine. OSA affects over 50 million Americans, with a large percentage remaining undiagnosed.

The trials investigated the effectiveness of retatrutide, an investigational drug from Eli Lilly, in treating OSA in adults who were overweight or obese. Retatrutide is currently being evaluated in phase 3 TRIUMPH trials for obesity and related metabolic conditions, though it has not yet received FDA approval. The FDA has previously cautioned about unauthorized versions of the drug being sold online for weight loss.

Study Design and Findings

The two randomized, phase 3 trials involved 691 adults diagnosed with moderate-to-severe sleep apnea and a body mass index (BMI) of at least 27. Participants were administered weekly injections of either retatrutide at doses of 4, 9, or 12 milligrams, or a placebo, over an 80-week period. The study population included both individuals without type 2 diabetes (243 participants) and those with the condition (448 participants).

Results showed that participants who received retatrutide experienced substantial weight loss, ranging from 12% to nearly 20% of their body weight. Crucially, these participants also exhibited a significantly lower number of breathing interruptions during sleep compared to the placebo group. Approximately 68% of participants treated with retatrutide reported more than a 50% improvement in their OSA symptoms, irrespective of their diabetes status.

The study also measured the reduction in hypoxic burden, which refers to the duration and severity of oxygen deprivation during sleep due to breathing disruptions. This burden decreased by about 75% in participants without type 2 diabetes and by 65% in those with the condition. Researchers concluded that retatrutide led to significantly greater reductions in the apnea-hypopnea index (AHI) than a placebo in overweight and obese adults with OSA.

While the study highlighted the drug's potential benefits, researchers noted the limitation of retatrutide's unapproved status by the FDA and emphasized the need for further studies to assess its long-term cardiovascular effects.

Expert Perspective

Dr. Virendra Somers, a cardiologist and professor of medicine at the Mayo Clinic and a co-author of the study, expressed surprise at the magnitude of benefits observed, particularly in patients with type 2 diabetes, and the notable reduction in sleep apnea severity. Somers commented on the underdiagnosis and undertreatment of OSA, calling the current period "very exciting" for sleep apnea patient care.

Sleep apnea is a known risk factor for serious health issues, including heart attacks, strokes, high blood pressure, and atrial fibrillation. The trial indicated that retatrutide use was associated with improvements in several cardiovascular risk factors, such as reductions in systolic blood pressure, LDL cholesterol, systemic inflammation, and neck circumference. Somers highlighted that blood pressure reduction in diabetic patients is particularly significant for mitigating future cardiovascular risk.

Furthermore, the drug showed positive effects on diabetes-related measures. In participants without diabetes, insulin levels dropped by over 50%. Among those with type 2 diabetes, a significant portion experienced improvements, with 40% transitioning from diabetes to prediabetes and another 40% no longer meeting the diagnostic criteria for diabetes.

Researchers attributed these improvements primarily to the weight loss achieved with retatrutide, which can consequently lead to better sleep quality and reduced sleep-related impairments.