SURMOUNT-OSA topline: tirzepatide cuts sleep apnea events by up to two thirds

Eli Lilly announced on April 17, 2024 that tirzepatide significantly reduced the severity of obstructive sleep apnea in two phase 3 trials of adults who also had obesity, hitting all primary and key secondary endpoints ^[1]. The company said it plans to file the data with the U.S. Food and Drug Administration and other regulators beginning mid-year, which could make tirzepatide the first drug approved to treat the underlying breathing disorder rather than just daytime sleepiness ^[1][2].

Tirzepatide is sold as Zepbound in the U.S. for chronic weight management and as Mounjaro in some markets outside the U.S. ^[1].

What the trials measured

The SURMOUNT-OSA program (NCT05412004) randomized 469 adults 1:1 to tirzepatide at a maximum tolerated dose of 10 mg or 15 mg once weekly, or to placebo, for 52 weeks, at sites in the U.S., Australia, Brazil, China, Czechia, Germany, Japan, Mexico and Taiwan ^[1]. Participants started at 2.5 mg and stepped up by 2.5 mg every four weeks until they reached their maximum tolerated dose ^[1].

The main measure was the apnea-hypopnea index, or AHI, which counts how many times per hour of sleep a person's breathing is blocked or restricted ^[1].

Study 1 enrolled people not using positive airway pressure (PAP) therapy. At 52 weeks, using the efficacy estimand, tirzepatide lowered AHI by 27.4 events per hour versus 4.8 for placebo — a 55.0% drop compared with 5.0% ^[1]. Body weight fell 18.1% with tirzepatide and 1.3% with placebo ^[1].

Study 2 enrolled people who were on PAP and planned to stay on it. Tirzepatide lowered AHI by 30.4 events per hour versus 6.0 for placebo, a 62.8% reduction compared with 6.4% ^[1]. Weight fell 20.1% versus 2.3% ^[1].

Lilly also reported a second, more conservative analysis (the treatment-regimen estimand) that counts data regardless of whether people stayed on treatment. Those numbers were somewhat smaller: in Study 1, a 25.3-event drop versus 5.3 for placebo, and a 50.7% versus 3.0% reduction ^[1][2]. In Study 2, the figures were 29.3 versus 5.5 events and 58.7% versus 2.5% ^[1]. Weight loss in that analysis was 17.7% and 19.6% in the two studies ^[1].

Lilly noted the near-20% average weight loss came in a group that was about 70% male, a population that generally loses less weight on incretin drugs than women do ^[1].

Side effects looked like those in earlier tirzepatide trials. The most common were gastrointestinal and generally mild to moderate: diarrhea, nausea and vomiting in Study 1, and diarrhea, nausea and constipation in Study 2 ^[1].

Why it matters for patients

Until now, drug treatment for obstructive sleep apnea has targeted the excessive sleepiness it causes, not the airway collapse itself ^[1]. Lilly cited figures that OSA affects 80 million U.S. adults, including more than 20 million with moderate-to-severe disease, and that 85% of cases go undiagnosed ^[1]. The disorder is linked to high blood pressure, coronary heart disease, stroke, heart failure, atrial fibrillation and type 2 diabetes ^[1].

The results also suggest a pattern that matters beyond sleep apnea: a weight-loss drug improving a specific condition driven by excess weight. Notably, the improvement showed up both in people who could not or would not use PAP machines and in people who kept using them ^[1].

Several things are not answered by this announcement. It is a topline company press release, not a peer-reviewed publication, and it does not report p-values, the share of people whose apnea resolved, changes in symptoms like daytime sleepiness, or whether anyone was able to stop PAP therapy ^[1]. There is no head-to-head comparison with PAP. Whether insurers would cover tirzepatide for sleep apnea, and at what cost, was not addressed ^[1][2]. FDA approval for this use had not been granted as of the announcement; Lilly said it has Fast Track designation for moderate-to-severe OSA with obesity ^[1].

What happens next

Full SURMOUNT-OSA results were scheduled for presentation at the American Diabetes Association's 84th Scientific Sessions on June 21, 2024 at 3:45 p.m. ET, with submission to a peer-reviewed journal ^[1]. Lilly said regulatory submissions to the FDA and other agencies would begin mid-year 2024 ^[1].