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Tirzepatide May Help Treat Sleep Apnea in People With Obesity

— Zepbound met primary and secondary endpoints, with or without CPAP

MedpageToday

ORLANDO -- Tirzepatide (Zepbound) improved symptoms of moderate-to-severe obstructive sleep apnea (OSA) in people with obesity, regardless of positive airway pressure (PAP) use, the phase III SURMOUNT OSA trials found.

For those not on PAP (trial 1), tirzepatide led to a mean change at week 52 in the apnea-hypopnea index (AHI) of -25.3 events per hour, as compared with -5.3 events per hour for placebo (estimated treatment difference of -20.0 events, 95% CI -25.8 to -14.2, P<0.001).

Mean change in AHI at week 52 among the PAP users (trial 2) was -29.3 events per hour with tirzepatide compared with -5.5 events with placebo (estimated treatment difference -23.8 events, 95% CI -29.6 to -17.9, P<0.001), reported Atul Malhotra, MD, of the University of California San Diego, at the annual American Diabetes Association Scientific Sessions.

"We have a potential new treatment for obstructive sleep apnea to add to existing therapies," said Malhotra.

The findings don't necessarily mean patients can ditch their continuous positive airway pressure (CPAP) machines, Malhotra said. "I'm a big believer that CPAP ... is first-line therapy for obstructive sleep apnea, but that doesn't address the obesity-related cardiometabolic complications," he said. "My belief will be treating both obesity and sleep apnea is the way to go."

The more weight you lose, the better, Malhotra told 鶹ý. "Some people say for every pound you lose, the less sleep apnea you have. Other people think there's a threshold where you get below a certain weight and sleep apnea goes away. Clinical experience suggests it's quite variable."

Results of the trials were simultaneously published in the .

Tirzepatide showed significant improvements in all prespecified key secondary endpoints in both trials. Systolic blood pressure improved with tirzepatide from baseline, with reductions of 9.5 mm Hg in trial 1, and 7.6 mm Hg in trial 2, which Malhotra said was "perhaps the most striking result."

"The improvement in systolic blood pressure that was seen with tirzepatide was substantially larger than effects seen with CPAP therapy alone and indicate that tirzepatide may be an attractive option for those patients who seek to reduce their cardiovascular risk," observed Sanjay Patel, MD, of the University of Pittsburgh, in an .

The benefits of tirzepatide for weight loss also could be expanded to patients who may benefit from second-line treatments for OSA like mandibular-advancement devices or hypoglossal-nerve stimulation, Patel suggested.

Initially approved for type 2 diabetes in 2022 (under the brand name Mounjaro), tirzepatide, a combination glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, gained approval for adult chronic weight management late last year.

In 234 and 235 participants were divided into trials 1 and 2. Trial 1 included participants who were unable or unwilling to use PAP therapy, while trial 2 included participants who had been using PAP therapy for at least 3 months and planned to continue it during the trial.

All participants had obesity (BMI of ≥30 or ≥27 in Japan) and a diagnosis of moderate-to-severe obstructive sleep apnea (AHI ≥15 events per hour). Diabetes, a diagnosis of central or mixed sleep apnea, and major craniofacial abnormalities were some exclusion criteria. Male enrollment was capped at 70%.

At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2. Average BMI was 39.1 and 38.7, respectively.

The starting tirzepatide dose was 2.5 mg once weekly, which was increased by 2.5 mg every 4 weeks until participants reached the maximum tolerated dose of 10 mg or 15 mg in week 20. All participants received regular lifestyle counseling sessions regarding nutrition; they had a 500 kcal/day deficit and at least 150 minutes/week of physical activity.

Body weight reductions were 17.7% in trial 1 and 19.6% in trial 2 -- not as high as they were in the original SURMOUNT-1 trial underpinning tirzepatide's approval for chronic weight management. This was "likely related to duration of therapy and gender balances in the studies," Malhotra said.

The most common side effects in SURMOUNT OSA were gastrointestinal, which were generally mild to moderate. Most common were diarrhea, nausea, vomiting, and constipation.

Two cases of acute pancreatitis occurred in the trial 2 tirzepatide group. Five cases of severe or serious depressive disorder or suicidal ideation or behavior events occurred across both trials (two with tirzepatide and three with placebo).

Although discontinuation was low (3-4%), Patel pointed out that real-world data indicates around half of patients who start treatment with a GLP-1 receptor agonist for obesity discontinue therapy within 12 months. Adherence to CPAP therapy also tends to be suboptimal, he noted.

"It is likely that any incorporation of tirzepatide into treatment pathways for obstructive sleep apnea will not diminish the importance of long-term strategies to optimize adherence to treatment," he said.

Drugmaker Eli Lilly said it submitted tirzepatide for the treatment of moderate-to-severe OSA in patients with obesity to the FDA. The company expects regulatory action as early as the end of the year.

  • author['full_name']

    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The trial was funded by Eli Lilly.

Malhotra reported relationships with Eli Lilly, Healcisio, LivaNova USA, Sunrise, University of California San Diego, and ZOLL Medical Corporation. Several co-authors reported disclosures, including relationships with Eli Lilly.

Patel reported relationships with Apnimed, Bayer HealthCare Pharmaceuticals, Breathe PA, Lilly, NovaResp Technologies, Philips, and Powell Mansfield.

Primary Source

New England Journal of Medicine

Malhotra A, et al "Tirzepatide for the treatment of obstructive sleep apnea and obesity" N Engl J Med 2024; DOI: 10.1056/NEJMoa2404881.

Secondary Source

New England Journal of Medicine

Patel SR, et al "Entering a new era in sleep-apnea treatment" N Engl J Med 2024; DOI: 10.1056/NEJMe2407117.