Obesity is a chronic disease affecting over 670 million adults globally, with multiple complications including obstructive sleep apnea (OSA). Substantial weight loss in patients with obesity-related OSA can reduce or even eliminate OSA as well as reduce sleepiness and improve cardiometabolic health. Past data from the University of Pennsylvania group suggests that these improvements exceed those that occur with device-based OSA therapies like CPAP which continue to be the first-line of therapy.
Resistance to weight management as a first-line strategy to combat OSA could arise from the complexities in delivering and maintaining adequate weight management, particularly in sleep clinic settings. Another issue is that almost all treatments prior to the past few years have resulted in only modest long term weight loss.
Recently, the developments of new drugs like semaglutide (Ozempic, Wegovy) and Tirzepatide (Mounjaro) have revolutionised drug therapy of obesity and overweight producing average weight loss in the range of 15-25%. The makers of current weight loss drugs Eli Lilly and Novo Nordisk have had staggering one year increases in their share price of 56% and 77% respectively. Meanwhile, stock market analysts have punished the ResMed share price by 30% resulting in a vocal pushback by their management. So, how should a patient view this?
New weight loss drugs, formerly called incretins and now nutrient stimulated hormones, are revolutionary and will change management of weight loss and no doubt, sleep apnea over the next few years. How much will depend on a number of factors and there have been no head to head comparisons with CPAP.
One advantage of these drugs is that they have a clear benefit in reducing blood fats, blood glucose and blood pressure and prevent the development of fatty liver and diabetes. There's no evidence that CPAP treatment results in either weight loss or improvement with these complications of obesity. These drugs work by making the body more sensitive to insulin, reducing appetite and reducing fat in the liver. There is experimental research in animals which suggest that the drugs also have a role in protecting the brain from dementia, but human studies are lacking.
There is a new research study called SURMOUNT OSA which will be completed in March 2024. The lead site in Australia and Asia for this study is based at the Woolcock Institute of Medical Research and Professor Ron Grunstein is part of the global steering committee for the trial. SURMOUNT OSA is comparing the effectiveness of Tirzepatide (Mounjaro) for weight loss and reducing sleep apnea severity in patients with sleep apnea. Half the patients are on active drug and half on placebo, half are on CPAP, half are not users and it is being run across a number of countries recruiting 400 patients in a one year protocol. Results from this study should be available in May 2024 and will be pivotal to understanding the role of these drugs in sleep apnea as well as understanding how much weight needs to be lost to reduce sleep apnea to a level that will not require CPAP treatment.
There is a large pipeline of these drugs being developed by Eli Lilly, Novo Nordisk, Pfizer and multiple pharmaceutical companies. At the moment only Semaglutide and Tirzepatide are available in Australia and involve weekly injections under the skin which are simple to administer. Side effect rates compared to placebo are low and less than 8% of patients have trouble tolerating nausea and diarrhea that are occasional side effects. Semaglutide is hard to obtain at the moment but the private cost is approximately $140 per month. If you consider the reduction in food consumed and the positive health outcomes, it could be argued that such a drug is cost effective. Semaglutide is covered by the PBS for patients with diabetes. At the moment, Tirzepatide has just been introduced and is significantly more expensive however with increasing availability and utilisation as well as increased competition from new drugs, we would expect that such drugs will significantly come down in price.
The implications of this new sleep apnea therapy approach will mean that sleep physicians will need to understand these new treatments for sleep apnea as they will be used in patients with or without CPAP. Sleep apnea can be no longer considered a disease where CPAP is the central therapy. Whether this affects the earnings of CPAP companies is a different matter and time will tell. Importantly sleep physicians will need to train in the management of patients with these drugs and GP's will have to upskill in both their management of sleep apnea and obesity. The relatively new profession of obesity medicine will also play a role. The Woolcock Institute are commencing a new study called TRIUMPH-2 which is looking at an even more effective weight loss drug called Retatrutide which can deliver an average weight loss of approximately 30%. TRIUMPH-2 is a 21-month study specifically in people with type 2 diabetes.
New Studies commenced at the Woolcock Institute - VOLUNTEERS REQUIRED
Several new studies have commenced at the Woolcock Institute of Medical Research in the last few months which are currently seeking participants.
Brain Cleaning in Obstructive Sleep Apnea
This National Health and Medical Research Council funded study aims to investigate whether there is a change in the brain's waste management system in patients who have severe obstructive sleep apnea (OSA). It will look at how the levels of certain markers of dementia change in the blood over a 5-week study period.
Currently, continuous positive airway pressure (CPAP) therapy is the gold standard clinical treatment for OSA, and the research team aims to monitor changes in markers for dementia after 2 weeks of usual CPAP treatment (when the patient has minimal to no symptoms of OSA) and after 2 weeks of having no CPAP treatment (when the patient's OSA will return).
Eligible Participants will undergo two overnight sleep sessions and one medical check-up visit throughout the length of the study. During the overnight sleep sessions, they will have a sleep study performed with high-density EEG and have a cannula inserted in the arm for a 24-hour period for hourly blood collection.
The study team are looking for participants who are aged between 35-65 years, have confirmed severe obstructive sleeap apnea via sleep study performed within the last two years and have been using CPAP for at least 3 months (minimum of 6 hours per night) and are willing to withdraw from using their CPAP machine at specified times while during the study.
For more information, please visit the study website at www.braincleanzzz.au
TRIUMPH-2 for Weight loss and Type 2 Diabetes
The Woolcock Institute is a site for the recently commenced global TRIUMPH-2 study sponsored by pharmaceutical company Eli Lilly. This study is a clinical trial for people with excess weight and type 2 diabetes. It is testing a new weight loss medication. Participants both with and without sleep apnea may be able to take part in the study – there will be slightly different study assessments for those who have sleep apnea, compared to those who don’t. The study team are looking for participants who are over 18 years of age, have type 2 diabetes, a BMI of 27 or higher, are willing to give themselves weekly injections and are able to take part in the full length of the study which is 1 year and 9 months.
For more information about the study, please contact claudia.harper@woolcock.org.au or visit here.