The benefits of the GLP1-RA for OSA in a new study correlate with weight loss, which reached 20% in some patients.
Obesity goes hand in hand with sleep apnoea, but what if there was a way you could reduce body fat and apnoeic episodes at the same time?
New research findings, published in the New England Journal of Medicine and presented in part of last month’s American Diabetes Association Symposium, found tirzepatide – a GLP-1 receptor antagonist like semaglutide – improves OSA, obesity and blood pressure in adults.
The randomised controlled study of 450 obese people with moderate to severe OSA found that using tirzepatide for a year more than halved the severity of the OSA, even in people not using CPAP therapy. In patients who combined CPAP therapy and tirzepatide, the reduction in severity was over 60%.
Weight loss was believed to be the major mechanism with the reduction in weight in the tirzepatide group correlating directly with the reduction in the number of apnoeic episodes.
“This new drug treatment offers a more accessible alternative for individuals who cannot tolerate or adhere to existing therapies,” said Professor Atul Malhotra, the lead author and director of sleep medicine at UC San Diego Health.
The SURMOUNT-OSA trials recruited more than obese 450 adults diagnosed with moderate-to-severe OSA (15 or more apnoeic or hypopnoeic events per hour) from nine countries.
Half of the patients were unwilling or unable to use a CPAP device (study 1), while the other half had were using CPAP therapy and had been for at least three months (study 2). Patients were randomised to receive weekly injections of tirzepatide or placebo for 12 months.
Tirzepatide was started at 2.5mg per week and increased by that amount every four weeks until the maximum tolerated dose of either 10 or 15mg per week was achieved.
Participants also received regular diet and exercise counselling throughout the study. After 12 months , patients on tirzepatide had an average of 27.4 (study 1) and 30.4 (study 2) fewer apnoeic or hypopnoeic events per hour compared to baseline, while patients receiving placebo had 4.8 (study 1) and 6 (study 2) fewer events per hour. This corresponds with a 55% reduction in OSA severity for study 1 participants, and a 63% reduction in severity for participants in study 2.
The reduction in OSA severity was found to correlate with a reduction in body weight. The tirzepatide group had an 18-20% reduction in body weight , compared to a 2-5% reduction in the placebo group over the 12-month duration of the study. Reductions in blood pressure and inflammation were also observed following tirzepatide treatment.
“Reduction of body weight, specifically excess adiposity surrounding the upper airways (particularly tongue and soft palate fat) and in the abdomen, is predicted to improve OSA severity based of the frequency of respiratory events and the degree of oxygen saturation,” the study authors wrote in a paper outlining the methodology of the trials, published earlier this year in Contemporary Clinical Trials.
Over 70% of patients in both trials experienced adverse events, regardless of whether they received tirzepatide or placebo. The most common side effects were diarrhoea, constipation, nausea and vomiting. These were more common in the tirzepatide group than in those on placebo.
While the FDA previously approved tirzepatide for chronic weight management in adults with obesity in November 2023, the manufacturer, Eli Lilly is expected to seek approval from various regulatory agencies to use tirzepatide for moderate-to-severe obesity and OSA in the coming months.
Tirzepatide received TGA approval in December 2022 “for the treatment of adults with insufficiently treated type 2 diabetes mellitus as an adjunct to diet and exercise” either “as a monotherapy where metformin is not tolerated or contraindicated” or “in addition to other medicinal products for the treatment of type 2 diabetes”.
PBAC rejected an application for tirzepatide to be added to the PBS in July 2023, citing concerns around the economic evaluation while noting tirzepatide failed to outperform the PBS-listed semaglutide on weight loss and glycaemic control at lower doses.
The TGA’s medicine shortage reports database indicates that tirzepatide will be in shortage until at least the end of August due to an “unexpected increase in consumer demand”.