Tirzepatide sharply reduced sleep apnea events in two 52-week trials

Adults with moderate-to-severe obstructive sleep apnea and obesity who took tirzepatide for a year had far fewer breathing interruptions during sleep than those given a placebo, according to two phase 3 trials published June 21, 2024 in the New England Journal of Medicine ^[1][3]. Tirzepatide is the molecule in Mounjaro and Zepbound.

The results come from SURMOUNT-OSA, registered as NCT05412004, which was run as two separate double-blind, randomized trials ^[1][3]. People who were not using positive airway pressure, or PAP, when they enrolled were placed in trial 1; people already using PAP were placed in trial 2. Everyone was assigned, in equal numbers, to either placebo or the largest dose of tirzepatide they could tolerate — 10 mg or 15 mg — for 52 weeks ^[1][3]. Neither participants nor investigators knew who was getting which ^[1][3]. Eli Lilly funded the research, and some results were presented in June 2024 at the American Diabetes Association's 84th Scientific Sessions in Orlando ^[3].

The primary measure was the apnea-hypopnea index, or AHI, which counts apneas and hypopneas in an hour of sleep ^[1][3]. In trial 1, participants started with an average AHI of 51.5 events per hour and an average body-mass index of 39.1 ^[1][3]. After 52 weeks, AHI had dropped by an average of 25.3 events per hour among those on tirzepatide and 5.3 among those on placebo, a difference of 20.0 events per hour (95% confidence interval, 25.8 to 14.2 fewer; P<0.001) ^[1][3].

In trial 2, the starting averages were 49.5 events per hour and a BMI of 38.7 ^[1][3]. AHI fell by 29.3 events per hour with tirzepatide and 5.5 with placebo, a gap of 23.8 events per hour (95% CI, 29.6 to 17.9; P<0.001) ^[1][3].

Every prespecified key secondary measure also moved in tirzepatide's favor, the authors reported, including the percentage change in AHI and in body weight, hypoxic burden, patients' own reports of sleep impairment and disturbance, high-sensitivity C-reactive protein, and systolic blood pressure ^[1][3].

On safety, gastrointestinal complaints were the most commonly reported side effects and were generally mild or moderate ^[1][3]. Serious adverse events occurred in 7.5% of participants overall, with similar rates in the two treatment groups, and there were no deaths and no cases of medullary thyroid cancer ^[4]. Two cases of acute pancreatitis were adjudicated, both in people taking tirzepatide in the PAP-therapy trial ^[4]. Five severe or serious depressive or suicidal events were recorded: two among tirzepatide users and three among those on placebo ^[4].

Why it matters for patients

Sleep apnea is tied to serious cardiovascular problems, and excess body fat is considered one of its causes ^[1][3]. PAP machines are a standard treatment, and trial 2 tested tirzepatide in people who were already using one rather than instead of one ^[1][3].

These were not studies of everyone with sleep apnea. Participants were adults who had both moderate-to-severe sleep apnea and obesity, so what happens in people with sleep apnea and a normal weight has not been reported ^[1][3].

The trials also could not answer whether the drop in breathing events translates into fewer heart attacks, strokes or deaths. That outcome was not measured in the 52-week results ^[1].

No trial in these documents compared tirzepatide with semaglutide (Ozempic, Wegovy) or any other sleep apnea drug, and no such comparison has been reported ^[1][3]. Whether the benefit lasts past one year, or what happens after the drug is stopped, also has not been reported.

What happens next

A correction to the paper was issued October 17, 2024 in the same journal ^[1]. The print version ran October 3, 2024 ^[3]. Later commentary appeared in the American Journal of Respiratory and Critical Care Medicine in April 2025 ^[1]. Whether regulators would approve tirzepatide for sleep apnea, and how insurers would cover it for that use, is not addressed in these documents.