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Obstructive sleep apnea (OSA) is a common condition where the airway becomes obstructed when we sleep (more background in my previous blog here). Treatment is typically with positive airway pressure (PAP) machines (which people sometimes don’t want to use or are poorly tolerated), or oral appliances that move the lower jaw forward. There are currently no medications approved to treat OSA. As weight loss can improve OSA in people with obesity, it is of great interest to evaluate whether new/emerging highly effective weight management medication can improve this condition. Tirzepatide (Zepbound for weight management, Mounjaro for diabetes) has now been shown to be very effective to treat OSA in people with obesity, as published in the New England Journal of Medicine in conjunction with a presentation at the American Diabetes Association meeting.
The SURMOUNT-OSA trials included 469 people with moderate-to-severe obstructive sleep apnea and obesity, without diabetes. They conducted two studies, one in people who were unable or unwilling to use positive airway pressure (PAP) treatment (study 1) , and another in people who were on PAP and planned to stay on it during the trial (Study 2). In both studies, people were randomized 1:1 to receive either tirzepatide at maximum tolerated dose (10mg or 15mg weekly) or placebo, for 1 year. The primary endpoint was improvement in the apnea-hypopnea index (AHI), which is the number of events of restricted or blocked breathing per hour.
Participants were 70% male, baseline BMI of 39kg/m2, baseline weight around 115kg, baseline AHI of 51/h, and about two thirds of participants had severe OSA. In SURMOUNT-OSA Study 1 (people not on PAP), people in the tirzepatide group had an impressive reduction of AHI by 25.3 events per hour, vs a reduction of 5.3 events per hour in the placebo group. Weight loss was -17.7% with tirzepatide vs -1.6% with placebo. In SURMOUNT-OSA Study 2 (people on PAP), people in the tirzepatide group had a reduction of AHI by 29.3 events per hour, vs a reduction of 5.5 events per hour in the placebo group. Weight loss was -19.6% with tirzepatide vs -2.3% with placebo.
Importantly, almost half of people in the tirzepatide groups had an improvement of their OSA to the point where treatment of their OSA (eg with CPAP) may no longer be needed/recommended (vs 13-14% with placebo), defined by achieving an AHI <5/h, or 5-14/h without much in the way of symptoms (Epworth Sleepiness Scale <10). There was a reduction in hypoxic (low oxygen) burden with tirzepatide vs placebo, which is important, as hypoxic burden better captures the OSA-related risk of cardiovascular complications and death than the AHI.
Other health benefits were in keeping with other studies of tirzepatide (eg lowering of blood pressure and CRP, a marker of inflammation). Side effects were predominantly gastrointestinal in nature, in keeping with what is known of tirzepatide and the GLP1 medication class. There were two cases of pancreatitis in the tirzepatide group. There were five cases of severe/serious depression or suicidality, three of which were in the placebo group, two in the tirzepatide group.
Based on what we know about how much weight loss improves AHI, citing data from a recent meta analysis, ADA panelist Dr Louis Aronne commented that the effect of tirzepatide on sleep apnea is likely mediated by weight loss (vs other benefits of GLP1 based medication that seem to be largely independent of weight loss).
The only other weight management medication that has been evaluated as a treatment of OSA is liraglutide 3mg daily (Saxenda). Liraglutide resulted in a modest reduction in AHI of -12.2 events per hour vs -6.1 events with placebo, with weight loss of -5.7% and -1.6%, respectively. On this basis, we have recommended in our Canadian Obesity Clinical Practice Guidelines 2022 Pharmacotherapy Chapter that liraglutide 3mg can be considered in conjunction with health behavior changes in treating people with obesity and OSA (disclosure: I am the lead author of this chapter). However, because the improvement in OSA was modest, liraglutide is not approved as a treatment of OSA.
BOTTOM LINE: Tirzepatide is extremely efficacious to improve obstructive sleep apnea (OSA) and facilitate weight loss in people with OSA and obesity, likely as a result of the weight loss itself, with about half of people improving to the point where they may no longer need PAP machines.
Disclaimer: I am/have been an investigator in clinical trials of tirzepatide. I receive honoraria as a continuing medical education speaker and consultant from the makers of tirzepatide (Eli Lilly).
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