GIP/GLP-1RA effective in sleep apnoea with obesity


By Geir O'Rourke

25 Jun 2024

Treatment with dual GIP/GLP-1 receptor co-agonist tirzepatide has been shown to improve sleep apnoea severity and related cardiometabolic issues in people with obesity, an Australian and international trial has found.

The study is being hailed as heralding a ‘new era’ in the treatment of obstructive sleep apnoea (OSA), after a period of lagging integration of obesity management into the approaches for care of the condition.

By targeting obesity, tirzepatide has downstream effects on blood pressure, inflammation and vascular endothelial dysfunction that may deliver a more holistic approach to OSA that is not attained with mechanical treatments such as CPAP, researchers said.

Results from the industry-funded SURMOUNT-OSA trial were presented during a late-breaking symposium at the American Diabetes Association 84th Scientific Sessions in Orlando, Florida, last week and simultaneously published in the NEJM (link here).

The study included a total of 235 adults with moderate-to-severe OSA and obesity, including 19 from Australia, who were split across two substudies of tirzepatide therapy: one involving participants who were receiving stable CPAP therapy and one involving participants for whom CPAP therapy had failed or had proved unacceptable.

Over a period of 52 weeks, treatment with weekly subcutaneous injections tirzepatide at a dose of 10 to 15 mg as compared with placebo resulted in a reduction in weight of approximately 16 to 17% across both substudies.

This was accompanied by a reduction in the apnoea-hypopnea index (AHI) as compared with placebo (the primary end point) of 20 to 24 events per hour, a relative reduction in events of 48 to 56%.

Benefits were also found in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure (-7.6 and -3.7 mm Hg in each of the substudies), the researchers reported.

This change in AHI was considered clinically relevant, exceeding the minimum requirements for such per American Academy of Sleep Medicine standards, they wrote in the NEJM.

“Symptoms of obstructive sleep apnoea represent a substantial disease burden and increased risk of injury, including increased risk of motor vehicle accidents and work-related injuries.”

“The symptom severity in obstructive sleep apnoea may also be a predictor of increased risk of cardiovascular complications.”

“Therefore, it is clinically relevant that in the current trials, positive effects of tirzepatide on the participants’ sleep-related functioning and sleep disturbance were detected.”

The findings represent a “breakthrough in the history of treatment of obesity and sleep apnoea,” said according to Dr Louis Aronne of Weill Cornell Medicine, who discussed the study’s implications regarding treatment of patients with obesity-related OSA at the conference.

“The SURMOUNT-OSA trial demonstrates that treatment of obesity with tirzepatide is an effective treatment for OSA, and it’s possible that combination therapy with tirzepatide plus CPAP is really the optimal treatment for OSA and obesity-related cardiometabolic risk.”

Study co-author Professor Ron Grunstein of the Woolcock Institute, Sydney said the results were exciting because excess weight was the most common risk factor for OSA, responsible for about 60% of moderate-to-severe cases.

“I’ve not seen any medication in sleep apnoea that has actually produced such a dramatic result,” Professor Grunstein said.

“While it doesn’t surprise us in a way because we knew that these medications cause significant weight loss, we didn’t know how much it would improve sleep apnoea. So, I think it’s the first medication that really does the job.”

“It also has the added advantage of improving blood glucose control, blood pressure and lipid levels not seen with other sleep apnoea treatments.”

The most frequent adverse events were gastrointestinal-related and were generally mild to moderate, and transient, he said.

A commentary published in the NEJM said the evidence from the trial supported the use of tirzepatide to address coexisting obesity in patients with obstructive sleep apnea, with additional benefits in cardiometabolic risk factors.

“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,” the authors noted.

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