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Tirzepatide (Zepbound) injections reduced sleep apnea severity among patients with obesity, regardless of positive airway pressure (PAP) use, according to topline data from two phase III trials.

In the SURMOUNT-OSA 1 study, focused on patients not using PAP treatment, tirzepatide lowered average apnea-hypopnea events by 27.4 per hour from baseline measurements versus the average 4.8-per-hour reduction on placebo treatment. That represented a 55% reduction from baseline to 52 weeks, as compared with 5% with placebo.

The SURMOUNT-OSA 2 trial, with a population who used PAP, showed that tirzepatide led to an average apnea-hypopnea index (AHI) reduction from baseline measurements of 62.8% compared with 6.4% for placebo treatments.

Both trials thus met their primary endpoints, drug manufacturer Eli Lilly reported in a .

Unsurprisingly, tirzepatide -- which was approved last year for weight loss -- led to reductions in body weight in both studies, with an 18.1% reduction among non-PAP users (vs 1.3% on placebo) and a 20.1% reduction among PAP users (vs 2.3% on placebo).

Holly Lofton, MD, of NYU Langone in New York City, called the results regarding obstructive sleep apnea (OSA) promising.

"We know that tirzepatide causes significant weight loss," she told 番茄社区app. "So with that, we have a decrease in fat cell size, and part of that can be in the structures around the neck. When there's less fat around the neck, that can help patients get more air in when they're sleeping. We saw these improvements both in those with the CPAP [continuous positive airway pressure] device and without the CPAP device, so that could be one possible reason for that."

Another potential mechanism for the benefit, she suggested, "is when people lose weight, they have less fat cells around the abdomen that are pushing up on the diaphragm, which can make it hard for the lungs to expand when sleeping as well."

Sleep apnea occurs when the airway partially or fully collapses during sleep, and is associated with a number of health problems when unmanaged, including , complications with medicines and surgery, and more. OSA is more common and more severe in association with obesity, but treating the comorbidity can be challenging.

"We then tell that patient with sleep apnea to lose weight, but it's hard to lose weight when you have sleep apnea," said Lofton. "People get in this bind. And what happens, I believe, especially with sleep apnea, is the patient is then labeled as 'non-compliant,' but sometimes they simply can't tolerate the machine. I think this gives us some other options to be able to treat the sleep apnea with weight loss, without the device or with the device."

Dan Azagury, MD, of Stanford Health in Palo Alto, California, told 番茄社区app that these results only add to the importance of utilizing drugs like tirzepatide in weight-loss and weight-management strategies in the context of conditions like sleep apnea.

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist, initially approved for type 2 diabetes under the trade name Mounjaro. Other GLP-1 receptor agonists approved for weight management include semaglutide (Wegovy) and .

"We don't need more reasons to know that we should use these drugs and that they're useful," Azagury said. However, with the added bonus of OSA improvement, he said he hopes it helps "get these [drugs] covered more broadly and get them paid for -- because that's the biggest challenge that we face right now."

Both Lofton and Azagury stressed that tirzepatide and similar medications are crucial for patients, as they provide an option to home in on obesity as an underlying cause for some health conditions, rather than treating that condition in isolation.

Azagury also highlighted the difficulties that can come with obesity and weight loss, including bias patients may face.

"Obesity is a condition that has all these very significant effects on your health. And there's a lot of bias against people with obesity. It is truly a condition that leads to a degradation of your health on multiple aspects, this being one of them. So being able to treat the underlying condition before you get the complications is a very logical thing to do," he said. "If you're talking about sleep apnea leading to other pulmonary complications and cardiovascular complications, treating [it] early is the best thing we can do."

The two trials included a total of 469 participants across nine countries who had a body mass index of at least 30 and an AHI of at least 15. Patients were randomized 1:1 to receive double-blind treatment with either tirzepatide or a placebo.

The safety profile of tirzepatide in these trials was similar to that in previous studies. Gastrointestinal adverse events were the most commonly reported, specifically diarrhea, nausea, vomiting, and constipation; these were typically mild to moderate in severity.

Tirzepatide was initially dosed at 2.5 mg, rising 2.5 mg every 4 weeks in both trials to either 10 mg or 15 mg. Doses were injected subcutaneously in the abdomen, thigh, or upper arm once per week for a total of 52 weeks.

The results from these trials are slated for presentation in June at the American Diabetes Association meeting in Orlando, Florida.

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