In a transformative breakthrough, the U.S. Food and Drug Administration (FDA) for the first time granted Zepbound (tirzepatide) as the first pharmacological intervention aimed at addressing moderate to severe obstructive sleep apnea (OSA) in obese adults. Approving Zepbound is an evolutionary step for solving the problem of OSA that affects millions of Americans, OSA is caused by a blocked airway during sleeping. Zepbound must be co-administered with a low-calorie diet, and it is suggested to increase physical activity level (exercise) during intake of this drug.
This is the first drug treatment to be specifically approved for some patients with OSA,” said Sally Seymour of the FDA’s Center for Drug Evaluation and Research (CDER), director of the division of pulmonology, allergy and critical care division. “It is a landmark development for patients with OSA.”
OSA is most common in the obese population and is usually treated by administering positive airway pressure (PAP) therapy, which keeps the airway open during sleep. However, PAP is contraindicated for some patients either due to intolerance or inability to adhere to the treatment.
Zepbound provides a completely new approach to this issue because it deals with the critical cause of OSA, which is obesity. It stimulates reactions to the intestinal hormone for reducing appetite and food ingestion, leading to a noticeable weight loss as well as further improvements in the symptoms of OSA.
The FDA approval was based on two large clinical trials (placebo-controlled and double-blind) with 469 adults who had moderate to severe OSA with obesity. Patients with type 2 diabetes were excluded. One of them was an analysis of the patients already using PAP, and the other had previously involved the patients unable or unwilling to use the standard therapy. Patients in both groups were then randomized to sub-groups and administered 10 or 15 mg of Zepbound or placebo weekly once for 52 weeks.
The apnea-hypopnea index (AHI), which measures the number of episodes of apnea (pause in breathing), and hypopnea (reduced breathing) per hour of sleep was the most significant predictor of successful outcomes in these clinical trials. At 52 weeks, the AHI of Zepbound-treated subjects was considerably decreased compared to the ones in the placebo group. A considerable number of subjects who were receiving Zepbound reached either remission or mild OSA with significant improvement in their symptoms and weight loss.
Regardless of its advantages, Zepbound has the following consequences and adverse effects: mild adverse events include vomiting, diarrhea, nausea, lethargy, and drug injection site reactions. Severe adverse event includes thyroid-C-cell carcinoma which has occurred during the animal studies. The FDA has indicated that Zepbound is contraindicated in patients who have medullary thyroid cancer or a family history of this illness or multiple endocrine neoplasia syndrome type 2.
Any patient with Zepbound who takes insulin or a medicine that stimulates insulin release must consult the health care provider about possibly reducing the dose of such medicines to minimize the risk of hypoglycemia. Depending on the severity of adverse effects, it is advised that healthcare professionals should closely monitor the patients for signs of pancreatitis, gall stones, altered mental status, kidney disease, and diabetic retinopathy and the patient should report it to the healthcare professional before use of Zepbound.
This approval brings new hope to adults with obesity who struggle with OSA, especially for those who cannot be treated with PAP. It is not a complete cure for the disease but rather provides a novel approach to addressing the connection between obesity and OSA possibly opening a pathway toward better sleep quality and better health outcomes for patients.
Reference: U.S. Food and Drug Administration (FDA). FDA Approves First Medication for Obstructive Sleep Apnea. 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea
