A new tool for treating sleep apnea

Obesity and obstructive sleep apnea often occur together but receive separate treatments. Now, a single drug may be used to treat both.

On December 20, 2024, the federal Food and Drug Administration approved use of Zepbound for obesity-related obstructive sleep apnea, the first drug to receive approval for this condition. It is already a popular prescription weight-loss drug. The FDA said Zepbound is intended to be used in combination with a regimen of more physical activity and a lower-calorie diet.

Zepbound (tirzepatide) is a GLP-1 (glucagon-like peptide-1) agonist, a group of drugs including Ozempic and Wegovy (both semaglutide) and Mounjaro (also tirzepatide) used to combat obesity and type 2 diabetes. In addition to tirzepatide, Zepbound also contains a GIP (glucose-dependent insulinotropic polypeptide) to lower appetite and decrease food consumption.

“It’s a landmark kind of study. For the first time, we have a new tool,” pulmonary and critical care physician Mir F. Shuttari, MD, said of the drug’s approval. “There has been quite a buzz in our sleep medicine community, and other doctors, too,”

Obstructive sleep apnea occurs during sleep, when the tongue and other throat muscles relax, blocking passage of air to the lungs. The affected person partially wakes to breathe, interrupting sleep. They may snore and gasp. This pattern repeats and can cause daytime sleepiness and affect ability to think clearly, according to the National Institutes of Health. If untreated, this condition can increase chances of heart attack, stroke and other problems, such as diabetes, chronic kidney disease and dementia.

Treatment has chiefly been use of a CPAP machine during sleep. These machines deliver air at a set pressure through masks that cover the mouth and nose or just the nose to keep the airway open.

Research Behind Approval

Sixty percent of people with moderate to severe obstructive sleep apnea are obese or morbidly obese, according to Dr. Shuttari, who runs the sleep laboratory at Falmouth Hospital.

“We find obesity is a major contributing factor,” he said.

The conditions are associated, however some people with moderate or even low weight can develop sleep apnea, and not all morbidly obese people have the condition, he added.

FDA approval was based upon two studies comparing 469 obese non-diabetic patients who either received weekly injections of Zepbound or a placebo, according to the FDA. Participants in one study used CPAP; those in the other study did not. Effectiveness was gauged using AHI (apnea-hypopnea index), which describes how often a person stops breathing or breathes shallowly during sleep. More people given Zepbound had significant drops in these events, with their apnea symptoms becoming milder or resolving. The Zepbound recipients also lost significant weight. The FDA concluded the improvement in AHI scores was “likely related to body weight reduction with Zepbound.”

Impact of FDA Approval

CPAP is still the gold standard for treatment, Dr. Shuttari said, and he has prescribed Zepbound in addition to CPAP - not as a replacement for it. The studies for FDA approval weren’t designed to determine if Zepbound alone could be effective, and more research is needed, he said.

“Some patients did drop their AHI to better than five, which we think is normal,” Dr. Shuttari said.

An AHI of 15 or higher indicates moderate sleep apnea, and an AHI of 30 or above indicates severe sleep apnea, he said. Use of CPAP lowers AHI, but better results can be obtained if patients lose weight before starting CPAP, he added.

Patients will have to meet certain criteria before he will prescribe Zepbound, Dr. Shuttari said. They need to be following guidelines for diet and exercise, using CPAP regularly and still be having trouble losing weight. People with diabetes, kidney disease, a family history of thyroid cancer or those who had pancreatitis would be excluded, as would young people under 18.

Patients on Zepbound and CPAP need to be monitored, he added. The drug suppresses appetite and thirst, which could cause users to become dehydrated, he said, which could worsen kidney issues. He said Zepbound may be less effective for people with diabetes.

“There’s a general feeling that people who are diabetic lose less weight on these GLP-1 medications.”

Trouble Sticking with It

While CPAP may be the gold standard of treatment, many patients don’t like using it and quit.

“In my experience, three years after prescribing CPAP, only 50 percent are being compliant,” Dr. Shuttari said.

Compliance also remains an issue with people taking GLP-1 medications. These drugs slow stomach emptying, causing a feeling of fullness; they also reduce desire to eat. They can cause side effects, such as diarrhea and constipation and, in some cases, pancreatitis. These digestive problems drive some people to stop taking them, Dr. Shuttari said.

“Half of these GLP-1 patients drop off.”

However, fewer side effects were reported in the Zepbound sleep apnea studies, he said.

Looking Ahead

More research may determine if Zepbound “could be available as an adjunct to CPAP or, in some cases, on its own,” Dr. Shuttari said.

With ongoing development of new GLP-1s and related drugs, he said “It’s an exciting time in the management of sleep apnea.”