Tirzepatide Improves Sleep Apnea Symptoms in Obese Patients With OSA

Treatment with tirzepatide led to an improvement in sleep apnea symptoms in patients with moderate to severe obstructive sleep apnea (OSA) and obesity, according to results from the SURMOUNT-OSA trial.

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist. It is the active ingredient in 2 Food and Drug Administration (FDA)-approved medications, Mounjaro for type 2 diabetes and Zepbound for chronic weight management.

The double-blind, phase 3 study (ClinicalTrials.gov Identifier: NCT05412004) included 2 groups of patients, those who were not on positive airway pressure (PAP) therapy (Study 1) and those who were (Study 2). To be included in the trial, patients had to have an apnea-hypopnea index (AHI) of at least 15 events/hour and a body mass index of at least 30kg/m². 

Study participants were randomly assigned to receive tirzepatide 10mg or 15mg (maximum tolerated dose) or placebo once weekly. The primary endpoint was the change from baseline in AHI at week 52. Secondary endpoints included the percent change in AHI from baseline and the percent change in body weight from baseline. 

Among OSA patients not on PAP therapy, the following efficacy results were reported for tirzepatide vs placebo at week 52:

• Efficacy estimand (efficacy prior to discontinuation of study drug):
  • Change in AHI from baseline: -27.4 events/hour vs -4.8 events/hour;
  • Percent change in AHI from baseline: -55.0% vs -5.0%; and
  • Percent change in body weight from baseline: -18.1% vs -1.3%.
• Treatment-regimen estimand (estimated average treatment effect regardless of treatment discontinuation):
  • Change in AHI from baseline: -25.3 events/hour vs -5.3 events/hour;
  • Percent change in AHI from baseline: -50.7% vs -3.0%; and
  • Percent change in body weight from baseline: -17.7% vs -1.6%.

Among OSA patients who were on PAP therapy and continued to use it, the following efficacy results were reported for tirzepatide vs placebo at week 52:

• Efficacy estimand:
  • Change in AHI from baseline: -30.4 events/hour vs -6.0 events/hour;
  • Percent change in AHI from baseline: -62.8% vs -6.4%; and
  • Percent change in body weight from baseline: -20.1% vs -2.3%.
• Treatment-regimen estimand:
  • Change in AHI from baseline: -29.3 events/hour vs -5.5 events/hour;
  • Percent change in AHI from baseline: -58.7% vs -2.5%; and
  • Percent change in body weight from baseline: -19.6% vs -2.3%.

The most common adverse events reported with tirzepatide were diarrhea, nausea, vomiting, and constipation.

“OSA impacts 80 million adults in the US, with more than 20 million living with moderate to severe OSA. However, 85% of OSA cases go undiagnosed and therefore untreated” said Jeff Emmick, MD, PhD, senior vice president, product development, Lilly. “Addressing this unmet need head-on is critical, and while there are pharmaceutical treatments for the excessive sleepiness associated with OSA, tirzepatide has the potential to be the first pharmaceutical treatment for the underlying disease.”

Additional data from the trial is expected to be presented at the American Diabetes Association’s 84th Scientific Sessions on June 21, 2024. The Company plans to submit the results from SURMOUNT-OSA to the FDA for regulatory review beginning mid-year.