Weight-Loss Drug Tirzepatide Reduces Severity of Obstructive Sleep Apnea

Reducing body weight with tirzepatide (Zepbound; Eli Lilly) decreases how often sleep is disrupted for patients who have moderate-to-severe obstructive sleep apnea (OSA) and obesity, results from the SURMOUNT-OSA study show.

The topline results, which were announced in April 2024, were fleshed out this past weekend at the American Diabetes Association Scientific Sessions and in a simultaneous New England Journal of Medicine publication. In addition to improving the apnea-hypopnea index (AHI), which represents the number of events during an hour of sleep, tirzepatide improved patient-reported sleep impairment and disturbances, markers of inflammation, and systolic blood pressure, report investigators.

Some patients saw an AHI reduction of nearly 60% from baseline, far greater than the roughly 3.0% reduction from baseline in placebo-treated patients.  

“This change is considered clinically relevant,” according to lead investigator Atul Malhotra, MD (University of California, San Diego), and colleagues. “The reductions in AHI were also accompanied by meaningful improvements in hypoxic burden, which better captures the obstructive sleep apnea-related risk of cardiovascular complications and death.”

To TCTMD, Malhotra said obesity is a known risk factor for OSA: around 60% to 70% of patients with sleep apnea are obese. “We know from prior studies that tirzepatide is quite an effective treatment for obesity, but we currently don't have any pharmacotherapy for sleep apnea,” he said. “It made logical sense to go ahead and look at whether people with obesity who have sleep apnea would benefit from tirzepatide compared with placebo.”

The current study, which lasted just 52 weeks, was not designed to assess clinical outcomes, but tirzepatide is being tested in a large-scale morbidity and mortality trial known as SURMOUNT-MMO. Other efforts to treat OSA through weight loss—with potential benefits for the heart—also are afoot. Last week, MOSAIC, an observational study from the Cleveland Clinic, showed that reducing body weight with bariatric surgery in patients with obesity and moderate-to-severe OSA reduced the risk of MACE and all-cause mortality by more than 40% over 10-year follow-up when compared with those not treated surgically.

Surgeon Ali Aminian, MD (Cleveland Clinic, OH), who led the MOSAIC analysis, said that patients with moderate-to-severe OSA need to “lose large amounts of weight to see any benefit in their lives” and it doesn’t matter how that’s achieved. Overall, he views SURMOUNT-OSA as complementary to their surgical study. “They both show that if we help people lose weight, we can improve the outcomes of sleep apnea,” Aminian told TCTMD.

He also argued that the clinical guidelines for sleep apnea, which recommend positive airway pressure (PAP), oral devices, changing sleep positions, or dietary and lifestyle changes, need to be revamped to highlight these more effective therapies for weight loss.  

Nishant Shah, MD (Duke University Medical Center, Durham, NC), a preventive cardiologist, said SURMOUNT-OSA suggests that nonsurgical weight loss with the novel weight-loss medications can have a promising impact on OSA and other cardiometabolic parameters. There is an “urgency to aggressively battle obesity” in the United States, he told TCTMD, and these latest results support its treatment in various clinical settings.

Sleep Apnea Impact

Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, was approved for chronic obesity last year. It is indicated for patients who are obese or overweight (body mass index ≥ 27 kg/m²) with at least one weight-related condition, such as hypertension, dyslipidemia, type 2 diabetes, CVD, or OSA. It is also approved, under the trade name Mounjaro, for the treatment of adults with type 2 diabetes mellitus in conjunction with diet and exercise.

SURMOUNT-OSA involved two randomized, controlled trials of adults with OSA and obesity who were treated with the maximally tolerated dose of tirzepatide (10 or 15 mg). Trial 1 included those treated concurrently with PAP, while trial 2 included those who were not. The mean AHI values were 51.5 and 49.5 events per hour at baseline in trials 1 and 2, respectively, and the majority of people had severe OSA, defined as 30 or more disruptions per hour. Nearly three-quarters of those randomized had hypertension, and approximately 80% had dyslipidemia.

Treatment with tirzepatide significantly reduced the AHI index, the studies’ primary endpoint, when compared with placebo-treated patients in both trials 1 and 2 (treatment difference of 20.0 and 23.8 events per hour, respectively; P < 0.001 for both).

The more weight you lose, the more your sleep apnea improves. Atul Malhotra

There were also improvements favoring tirzepatide when AHI was assessed as a percent change from baseline, as well as a greater number of patients who achieved a 50% or greater reduction in AHI. More patients treated with tirzepatide got down to an AHI of less than 5 (or AHI of 5 to 14 events per hour accompanied by a measure of less daytime sleepiness). High-sensitivity CRP concentrations were lowered to a greater extent with tirzepatide, as was systolic blood pressure. Two patient-reported measures related to sleep impairment and disruptions—PROMIS-SRI and PROMIS-SD—were significantly better in those randomized to tirzepatide.

“Everything went in the right direction,” said Malhotra of these secondary outcomes.  

In terms of weight loss, patients treated with tirzepatide in trial 1 lost 17.7% of their body weight at week 52 compared with a loss of 1.6% in the placebo arm. In those not using PAP, the reduction from baseline was 19.6% with tirzepatide versus 2.3% in the placebo group.  

Just this month, Malhotra and colleagues published a meta-analysis of studies reporting weight loss (with any intervention, including surgery, lifestyle changes, and pharmacotherapy) as well as lower AHI in people with OSA and obesity. The improvement in AHI was correlated with the magnitude of weight loss.

“The more weight you lose, the more your sleep apnea improves,” said Malhotra.

Improving Patient-Centered Outcomes

In an NEJM editorial, Sanjay Patel, MD (University of Pittsburgh, PA), says the improvement in systolic blood pressure with tirzepatide was much larger than what’s been observed with continuous PAP therapy alone, suggesting that this might be an attractive option for physicians looking to lower the CVD risk of their patients. Whether this drug reduces major clinical outcomes will require patience for SURMOUNT-MMO to run its course, though. Results of that trial aren’t expected until 2027.

Also uncertain is whether treatment with tirzepatide reduces patient-centered outcomes, Patel said, “because a change in the AHI has not been validated as a surrogate marker of clinically relevant endpoints.” He also points out that research experience with the PROMIS metrics is not extensive, something the researchers acknowledge as a limitation.

“Additional analyses of the effects of tirzepatide on a broader range of patient-reported outcome measures by the SURMOUNT-OSA team will be eagerly awaited to evaluate the potential utility of tirzepatide as a sole treatment for obstructive sleep apnea,” writes Patel.