How Does Zepbound Work?
The GLP-1 receptor agonist Zepbound fights obesity by mimicking two metabolic hormones in the body that stimulate insulin secretion and sensitivity after a person eats. The drug regulates the body’s blood sugar levels, slows down digestion and reduces appetite, which makes a person feel fuller, eat less, and lose weight.
Although it’s not completely known how Zepbound improves obstructive sleep apnea (OSA), it’s likely related to weight loss, because obesity is a factor that increases the risk of OSA, says Nathan Walker, MD, assistant professor of sleep medicine and memory and cognitive disorders, and program director of the Sleep Medicine Fellowship at the University of North Carolina in Chapel Hill.
“That’s through many mechanisms. For one, obesity causes direct compression of the upper airway with weight around the neck,” he says.
Another factor is that abdominal obesity reduces the functional capacity of the lungs, which then reduces lung inflation. “That reduces traction on the upper airway, making the upper airway more likely to collapse in sleep,” says Dr. Walker.
Zepbound Effective in Reducing the Severity of OSA
The approval of Zepbound for obstructive sleep apnea treatment is based on the results of two major studies from the SURMOUNT-OSA clinical trials, which enrolled a total of 469 adults with moderate-to-severe OSA and obesity. Participants were randomly assigned to receive either Zepbound (at 10 or 15 milligram doses) or a placebo once a week for 52 weeks.
In the first trial, none of the participants received continuous positive airway pressure (CPAP) therapy (the standard treatment for OSA), and in the second trial, only people using CPAP therapy were included.
In both trials, people taking either dose of Zepbound experienced a significant reduction in the number of apneas and hypopneas per hour, as measured by the apnea-hypopnea index (AHI).
Apneas are periods when a person stops breathing and hypopneas are instances where airflow is blocked which causes shallow breathing.
- Fifty percent of people on Zepbound with CPAP therapy and 42 percent of those using Zepbound without CPAP showed complete remission or a reduction to mild OSA, compared with just 14 percent and 16 percent in the placebo groups, respectively.
- Participants in the Zepbound groups achieved a significant decrease in body weight, with an average weight loss of 45 pounds (18 percent) compared with 4 pounds (2 percent) for those on placebo.
Because people who didn’t have obesity weren’t included in the trial, it’s unclear if Zepbound would help with sleep apnea in people who don’t have obesity.
“This question has not been tested in clinical trials. It would not be recommended to use GLP-1s outside the indications approved by the FDA,” says Ali El Solh, MD, MPH, a professor of medicine at the State University of New York in Buffalo, and supervisor of the sleep clinic at the VA Western New York Healthcare System.
What Does the Approval Mean for CPAP Therapy?
In the studies on tirzepatide and obstructive sleep apnea, patients had a roughly 50 percent reduction in the severity of their OSA on average, says Walker.
“On average, this would significantly reduce the severity of their OSA, but not necessarily eliminate it. So patients should not throw out their CPAP machines just yet,” he says.
Malhotra agrees that CPAP is still first-line treatment. “But it’s always been the case that we want to treat both sleep apnea and obesity,” he says.
Diet and exercise are still recommended, but Zepbound and other GLP-1 medications are more effective in helping people lose weight, says Malhotra.
“I think it’s important that people understand this approval doesn’t mean it’s the end of CPAP,” he adds.
Safety and Side Effects of Zepbound
Side effects of Zepbound in clinical trials for obesity and type 2 diabetes also include fatigue, allergic reactions (typically fever and rash), burping, hair loss, and gastroesophageal reflux disease.
“These drugs are considered relatively new agents and thus the long-term safety of these medications is yet to be established,” says El Solh.
Cost and Insurance Coverage May Remain a Barrier for Many People
Although Zepbound and other GLP-1 receptor agonist medications are “game changers” because of their benefits for obesity, sleep apnea, and cardiovascular risk factors, these drugs often remain outside the reach of people who need them the most because of their cost, says El Solh.
Insurance coverage for Zepbound for OSA isn’t yet known. How much a person can expect to pay depends on what type of insurance they have.
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