Tirzepatide significantly reduces sleep disorders

ORLANDO, Fla. — Diabetes and weight loss drugs Tirzepatide (Munjaro Type 2 diabetes; Zepbound obesity) is highly effective in reducing sleep disorders in obese patients, Obstructive sleep apnea Two new studies suggest that 40% to 50% of people with OSA no longer need to use continuous positive airway pressure (CPAP) machines.

Tirzepatide is a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. GlucagonGLP-1 (glutamate) receptor agonists, an antidepressant, also reduced C-reactive protein levels and systolic blood pressure, and patients taking the drug lost 18-20% of their body weight.

The SURMOUNT-OSA study “represents an important milestone in the treatment of OSA, providing a promising new treatment option that addresses both its respiratory and metabolic complications,” said lead author Atul Malhotra, MD, professor of medicine at UC San Diego and chief of the Department of Sleep Medicine at UC San Diego Health.

The two double-blind randomized controlled trials, which included obese patients with moderate to severe OSA, were conducted at 60 sites in nine countries. The results were presented at the 84th Scientific Session of the American Diabetes Association (ADA). Publish online In New England Journal of Medicine.

OSA affects 1 billion people worldwide and 30 million adults in the United States, many of whom go undiagnosed. Obesity is a common risk factor: according to the ADA, 40% of obese people have OSA, and 70% of people with OSA are obese.

Although CPAP is an effective and most commonly used treatment for OSA, many patients refuse to use the device, discontinue using it, or are unable to use it. If tirzepatide is ultimately approved by the U.S. Food and Drug Administration (FDA) for the treatment of OSA, it would be the first drug approved for the disease.

“This new drug treatment provides a more accessible alternative for people who cannot tolerate or comply with existing treatments,” Malhotra said.

Significant reduction in attacks and severity

Two studies enrolled patients with moderate to severe OSA (≥15 episodes per hour using the apnea-hypopnea index). [AHI]) and BMI 30 kg/m² or more. People who did not use CPAP devices were enrolled in Study 1, and people who used CPAP devices were enrolled in Study 2.

Participants received the maximum tolerated dose of tirzepatide (10 or 15 mg, one injection per week) or a placebo for one year. In study 1, 114 patients received tirzepatide and 120 received placebo. In study 2, 119 patients received tirzepatide and 114 received placebo. All participants received regular lifestyle counseling sessions on nutrition and were instructed to reduce their daily food intake by 500 kcal and to engage in at least 150 minutes of physical activity per week.

To ensure adequate representation of women, enrollment was limited to 70% males.

At baseline, 65% to 70% of participants had severe OSA, with an AHI scale of 30 or more attacks per hour, with a mean of 51.5 attacks per hour.

By the first year, patients taking tirzepatide experienced a reduction of 27 to 30 events per hour, compared with 4 to 6 events per hour in patients taking placebo.

Up to half of subjects receiving tirzepatide in both studies had fewer than five sleep events per hour or five to 14 AHI events and an Epworth Sleepiness Scale score of 10 or less. These thresholds “represent levels at which CPAP therapy is not recommended,” the authors wrote.

In patients receiving tirzepatide, systolic blood pressure also decreased from baseline to week 48 by 9.7 mm Hg in study 1 and 7.6 mm Hg in study 2.

The most common adverse events were diarrheanausea, and vomiting occurred in about one-quarter of patients taking tirzepatide. Acute pancreatitis In patients who took tirzepatide in Study 2.

Patients who received tirzepatide also reported a reduction in daytime and nighttime sleep disturbances, as measured using the Patient-Reported Outcomes Measurement Information System-Short Form scales for sleep-related disorders and sleep quality. Sleeping disorder.

Combining Tirzepatide with CPAP is best

write Accompanying editorialSanjay R. Patel, MD, noted that while clinical guidelines recommend incorporating weight loss strategies as part of OSA treatment, “the incorporation of obesity management into approaches to the treatment of obstructive sleep apnea has been slow.”

Half of patients discontinue CPAP therapy within three years, wrote Patel, a professor of medicine and epidemiology at the University of Pittsburgh School of Medicine and medical director of the Comprehensive Sleep Disorders Program at the University of Pittsburgh School of Medicine. “Effective drugs to treat obesity are therefore an obvious avenue to pursue,” he wrote.

Patel noted a significant reduction in the number of events on the AHI scale. He wrote that the improvement in systolic blood pressure was “substantially greater than the effect seen with CPAP therapy alone, indicating that tirzepatide may be an attractive option for patients wishing to lower their blood pressure.” Cardiovascular risk“

Patel noted that studies have shown high discontinuation rates with GLP-1 receptor agonists and expressed concern about whether patients not participating in clinical trials will continue with treatment.

Moreover, he writes, “Will the racial disparities in the use of GLP-1 receptor agonists among patients with diabetes mellitus only exacerbate already widespread disparities in the clinical treatment of obstructive sleep apnea by adding tirzepatide as a treatment option for obstructive sleep apnea without directly addressing treatment coverage policies?”

Commenting on the study during the results presentation, Louis Aronne, MD, said he believes the trial demonstrates that “tirzepatide plus CPAP for the treatment of obesity is the treatment of choice for obstructive sleep apnea and the cardiometabolic risks associated with obesity.” Aronne is the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medical College in New York.

Arone adds that there's still a lot to be learned: It's not yet clear whether tirzepatide had an independent effect in the OSA trial (other studies have found that the drug clearly reduced cardiovascular risk) or whether the positive results were primarily due to weight loss.

“I believe that over time we will find that this particular effect in sleep apnea is related to weight,” he said.

The study was supported by Eli Lilly and Co. Malhotra reports being a paid consultant for Lilly and Zoll Medical, and is a co-founder of Healthigio.

ADA 84th Scientific Sessions. Presented June 21, 2024.

N English J MedicineIt will be published online on June 21, 2024. Abstract, editorial

Alicia Ault is a freelance journalist based in St. Petersburg, Florida, whose work has appeared in publications such as JAMA and Smithsonian.com. You can find her at @aliciaault.