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Based on these results, tirzepatide could be first medication approved for treatment of obstructive sleep apnea in patients with obesity.
Treatment with tirzepatide, with and without a continuous positive airway pressure (CPAP) machine, had improvements in apnea-hypopnea index (AHI) from baseline to week 52 for individuals with obstructive sleep apnea (OSA) and obesity, according to results of the SURMOUNT-OSA (NCT05412004) trial. Based on these results, tirzepatide could be first medication approved for treatment of OSA in patients with obesity, said Louis J Aronne, MD, FACP, DABOM, from Weill Cornell Medicine, at the American Diabetes Association 84th Scientific Sessions.1
Image Credit: Vitalii Vodolazskyi - stock.adobe.com
“We know that substantial evidence over the past 25 years has shown that sleep and circadian disturbances are linked to obesity, diabetes, and cardiovascular disease through multiple biological mechanisms,” Esra Tasali, MD, from the University of Chicago, said in the session. “Given the large evidence linking insufficient sleep to diabetes outcomes, American Diabetes Association Clinical Practice Recommendations, recently added a sleep assessment as part of precision medicine in diabetes initiative.”1
OSA is a common sleep disorder that occurs when the airways are obstructed while sleeping. However, OSA has a variety of symptoms, presentation, and treatment response per patient, so personalized treatment is necessary, according to Tasali.1
Currently, there are a few, non-pharmacologic interventions, which include CPAP, a dental sleep apnea device, and hypoglossal nerve stimulation for those who are intolerant to CPAP.1
“CPAP really is an excellent treatment option for patients with symptomatic sleepiness, but obviously therapy may require a more nuanced individualized approach to treatment among those with non-sleepy sleep apnea,” Vaishnavi Kundel, MD, MS, Mount Sinai, said in the session.1
Weight loss combined with CPAP had greater effects on OSA, according to Kundel. Lifestyle interventions did have a greater effect on c-reactive protein (CRP), but blood pressure and insulin sensitivity were affected more with a combination approach.1
In the SURMOUNT-OSA trial, investigators conducted 2 separate trials: one that included patients who were not on PAP (Study 1) and patients who were not on PAP (Study 2). The population within the study was similar when stratified by country, geographical region, baseline AHI, and sex. Further, investigators restricted enrollment to 70% male, so more women could be accommodated into the study. Individuals were included in the study if they were aged 18 and older, had moderate to severe OSA, and a body mass index (BMI) over 30. Exclusion included individuals with diabetes or those planning for surgery related to sleep apnea or obesity.1,2
The primary end point was to demonstrate that tirzepatide at the maximum tolerated dose was superior to the placebo in changes of AHI. Key secondary end points included the percent change in AHI; patients with an AHI reduction of at least 50%; patients with an AHI of less than 5 events per hour; the percent change in body weight; the change in high-sensitivity CRP concentration; the change in scores on the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-related Impairment 8a (PROMIS-SRI), which accounted for daytime symptoms, and PROMIS Short Form Sleep Disturbance 8b (PROMIS-SD) scales, which accounted for nighttime symptoms; and the change in systolic blood pressure.1,2
The trial was conducted from June 21, 2022, to March 29, 2024, with a total of 234 individuals in Study 1 and 235 in Study 2. Overall, 82.9% completed the trial, with 91.5% in the tirzepatide group and 74.4% in the placebo group. Approximately 87.6% in the tirzepatide group adhered to treatment compared to 71.9% in the placebo group.2
Trial Name: Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea (SURMOUNT-OSA)
ClinicalTrials.gov ID: NCT05412004
Sponsor: Eli Lilly and Company
Completion Date: March 2024
In Study 1, the change in AHI at week 52 was approximately –25.3 events per hours with tirzepatide and –5.3 events per hour with the placebo. For trial 2, the primary endpoint was –29.3 events and –5.5 events, respectively. When looking at the efficacy estimand, the changes were –27.4 events and –4.8 events, respectively, and –30.4 events and –6.0 events, respectively.1,2
Aronne noted that this change is noted as clinically meaningful, meaning the average patient is going from severe OSA to moderate OSA.1
“So more than 4 out of 10 people who could not use the CPAP, no longer would need it, and more than 50% of those who are chronically using the CPAP [would no longer need it],” Aronne said.1
Furthermore, for severity, at baseline in Study 1, approximately 99% who had severe or moderate OSA decreased to 42% at 52 weeks and 20% had scores that no longer qualified for OSA. In Study 2, 99% of individuals with severe or moderate OSA decreased to 40% and 31% no longer qualifying for OSA.1
According to Atul Malhotra, MD, University of California, San Diego, the percent change in hypoxic burden decreased by 67% in Study 1 and 75% in Study 2. Patients in Study 1 and Study 2 also had 18% and 20% improvements in BMI, respectively. Furthermore, for patient reported outcomes between both studies, the PROMIS scores improved by 7.5 for daytime symptoms and approximately 5 for nighttime sleep disturbance.1
As for safety, approximately 79.8% of those treated with tirzepatide experienced adverse events and 76.7% with the placebo in Study 1 and 83.2% and 72.8%, respectively, in Study 2. The most common AEs were gastrointestinal related, which is consistent with prior data on glucagon-like peptide-1 medication, according to Malhotra.1
“The SURMOUNT-OSA trial demonstrates the 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 obstructive sleep apnea and obesity related cardiometabolic risk,” Aronne concluded.1
