An investigational weight-loss drug developed by Eli Lilly has demonstrated a significant reduction in breathing interruptions and other symptoms of obstructive sleep disorder across two clinical trials. The findings, published in The New England Journal of Medicine, evaluate retatrutide as a potential therapeutic option for individuals suffering from obesity-related sleep disturbances.
Obstructive sleep apnea impacts more than 50 million Americans, with estimates indicating that roughly 80% of cases remain undiagnosed, according to the National Sleep Foundation. The condition is closely linked to elevated risks for heart attacks, strokes, high blood pressure, and atrial fibrillation. Retatrutide is currently undergoing phase 3 TRIUMPH trials as a potential treatment for obesity and related metabolic conditions, though it has not yet received approval from the U.S. Food and Drug Administration. The FDA has previously issued warnings regarding unauthorized versions of the compound being marketed and sold online for weight loss.
The two randomized phase 3 trials collectively enrolled 691 adult participants diagnosed with moderate-to-severe sleep apnea who possessed a body mass index of at least 27. Of the total group, 243 participants did not have type 2 diabetes, while 448 participants managed the condition. Individuals were administered once-weekly injections of retatrutide at varying doses of 4, 9, or 12 milligrams, or were given a placebo, over an 80-week follow-up period.
Participants treated with retatrutide shed between 12% and nearly 20% of their baseline body weight and recorded substantially fewer breathing disruptions compared to those in the placebo group. Approximately 68% of trial participants achieved greater than a 50% improvement in obstructive sleep apnea symptoms, a trend that held true regardless of type 2 diabetes status.
Researchers also measured hypoxic burden, which tracks the severity and duration of low-oxygen episodes during sleep caused by breathing interruptions. The metric fell by approximately 75% among participants without type 2 diabetes and by about 65% among those with the condition. Investigators concluded that the compound produced significantly greater reductions in apnea-hypopnea index breathing interruptions than the placebo, driven largely by overall weight loss that helps improve sleep quality and reduce impairment.
Beyond respiratory metrics, participants experienced improvements in several cardiovascular risk factors, including systolic blood pressure, low-density lipoprotein cholesterol, systemic inflammation, and neck circumference. Dr. Virend Somers, a cardiologist, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and study co-author, noted that while the general outcomes aligned with expectations, the sheer magnitude of the benefit observed in patients with type 2 diabetes came as a surprise.
Among participants without diabetes, circulating insulin levels dropped by more than 50%. Meanwhile, among those managing type 2 diabetes, 40% transitioned from diabetes to prediabetes, and an additional 40% no longer met the clinical criteria for diabetes. Somers emphasized that reducing blood pressure serves as a critical determinant of future cardiovascular risk, particularly for diabetic patients, making the recorded reductions both unexpected and encouraging as further studies continue to examine the drug’s long-term cardiovascular outcomes.
