The first and only approved indication for obstructive sleep apnea is Tirzepatide

On December 20, 2024, Eli Lilly and Company (NYSE: LLY) announced that the US Food and Drug Administration (FDA) has approved Zepbound ®  Tirzepatide is the first and only prescription drug for adults with moderate to severe obstructive sleep apnea (OSA) and obesity. Zepbound may help improve sleep disorders in adults with moderate to severe obstructive sleep apnea and obesity. It should be used in conjunction with a low calorie diet and increased physical activity. This is the second indication Zepbound has obtained in the United States in just over a year, following FDA approval in November 2023 for adults with obesity or overweight and weight related medical issues.

OSA is often overlooked as' just snoring '- but it goes far beyond that Dr. Julie Flygare, President and CEO of Project Sleep, said. It is important to understand the symptoms of OSA and know there are treatment options, including new options like Zepbound. We hope this will spark more meaningful dialogue between patients and healthcare providers, and ultimately lead to better health outcomes

OSA is a sleep breathing disorder characterized by complete or partial collapse of the upper respiratory tract during sleep, which may lead to respiratory pauses (apnea) or shallow breathing (hypopnea), as well as decreased blood oxygen saturation and/or waking up from sleep. One of the signs of OSA is snoring, but fatigue, excessive daytime sleepiness, and disrupted sleep are also major symptoms, making this serious illness easily overlooked.

Nowadays, many cases of OSA go undiagnosed and untreated, and millions of people are at risk of serious health consequences, "said Patrik Jonsson, President and Executive Vice President of Lilly Cardiometabolic Health and Lilly America. Zepbound is the first medication that can significantly improve moderate to severe OSA and aid in long-term weight loss in obese adults. Nearly half of the clinical trial patients have seen this improvement, and they no longer have symptoms related to OSA, marking a crucial step in reducing the burden of this disease and its associated health challenges

experimental design 

SURMOUNT-OSA (NCT05412004) is a multicenter, randomized, double-blind, parallel, placebo-controlled primary protocol that compares Zepbound ®  The efficacy and safety of tilpotide and placebo in adults with moderate to severe obstructive sleep apnea (OSA) and obesity were studied in two parts. In Study 1, these adults were unable or unwilling to use positive airway pressure (PAP) therapy, while in Study 2, they had been receiving and planned to continue receiving PAP therapy during the trial period. According to the main protocol, 469 participants from the United States, Australia, Brazil, China, Czech Republic, Germany, Japan, Mexico, and Taiwan were randomly assigned in a 1:1 ratio to receive Zepbound's maximum tolerated dose (MTD) of 10 milligrams or 15 milligrams or placebo. The main objective of the two studies is to demonstrate that Zepbound outperforms placebo in terms of baseline changes in apnea hypopnea index (AHI) at 52 weeks.

SURMOUNT-OSA uses a weekly MTD of 10 milligrams or 15 milligrams. The initial dose of Zepbound is 2.5 milligrams, increasing by 2.5 milligrams every four weeks until the maximum tolerated dose is reached. Participants who tolerated 15 milligrams continued to take 15 milligrams as MTD. Participants who tolerated 10 milligrams but did not tolerate 15 milligrams continued to take 10 milligrams as MTD.

test result 

This approval is based on the results of the SURMOUNT-OSA Phase 3 clinical trial, which evaluated the efficacy of Zepbound (10 mg or 15 mg) in treating moderate to severe OSA in obese adults within one year, including whether to receive positive airway pressure (PAP) treatment.

In Study 1, Zepbound was approximately five times more effective than placebo in reducing respiratory interruption in adults who did not receive PAP treatment. Zepbound reduced respiratory interruption by 25 times per hour, while placebo reduced it by 5 times per hour. Adults who received Zepbound treatment in Study 1 lost an average of 45 pounds (18%), while those who received placebo treatment lost an average of 4 pounds (2%). In the key secondary outcome, tilpotide reduced mean AHI by 55.0% compared to baseline, while the placebo group reduced it by 5.0%.

In Study 2, Zepbound reduced respiratory interruptions by 29 times per hour in adults receiving PAP treatment, while placebo reduced them by 6 times per hour. After one year, 42% of adults receiving Zepbound treatment and 50% of adults receiving Zepbound and PAP treatment experienced relief or mild asymptomatic OSA, compared to 16% and 14% in the placebo group, respectively. In Study 2, Zepbound adults receiving PAP treatment lost an average of 50 pounds (20%), while adults receiving placebo treatment lost an average of 6 pounds (2%). In the key secondary outcome, tilpotide reduced mean AHI by 62.8% compared to baseline, while the placebo group achieved 6.4%.