SURMOUNT-OSA: Tirzepatide improves sleep apnea symptoms for adults with OSA plus obesity
Click Here to Manage Email Alerts
Key takeaways:
- Adults with OSA and obesity receiving tirzepatide had reductions in apnea-hypopnea index events and body weight.
- The improvements in OSA symptoms were seen regardless of PAP therapy.
ORLANDO — The GIP/GLP-1 dual agonist tirzepatide reduced symptoms of obstructive sleep apnea and improved multiple cardiometabolic markers for adults with obesity and obstructive sleep apnea, according to data from the SURMOUNT-OSA trial.
In findings presented at the American Diabetes Association Scientific Sessions and simultaneously published in The New England Journal of Medicine, adults receiving tirzepatide (Zepbound, Eli Lilly) had greater reductions in apnea-hypopnea index (AHI) events per hour, which is a measure of severity of obstructive sleep apnea (OSA), compared with placebo. The reduction was observed for adults using positive airway pressure (PAP) therapy and those who did not use PAP therapy. Atul Malhotra, MD, vice chair of medicine for research and professor of medicine at University of California, San Diego, said tirzepatide could change the way providers approach OSA if the medication receives a new indication from the FDA.
“There are currently no approved therapies for OSA in the pharmacology space whatsoever,” Malhotra told Healio during a press conference. “There’s no drug that address both [obesity and OSA]. There’s no therapy that addresses OSA with a drug yet. There’s various studies that are looking at different drug combinations, but there’s nothing approved for sleep apnea.”
SURMOUNT-OSA consisted of two phase 3, double-blind randomized controlled trials. Both trials enrolled adults with moderate to severe OSA with 15 or more AHI events per hour plus obesity. The first trial included 234 adults who were not using PAP therapy (mean age, 47.9 years; 67.1% men, 65.8% white), and the second trial included 235 adults who used PAP therapy for at least 3 consecutive months before the trial and planned to continue using it during the study (mean age, 51.7 years; 72.3% men; 73.1% white). After a 4-week screening period, adults in both trials were randomly assigned, 1:1, to once-weekly tirzepatide or placebo for 1 year. Tirzepatide was titrated up to 10 mg or 15 mg per week. AHI was assessed at screening, week 20 and week 52. The primary endpoint of the trial was change in AHI from baseline to 52 weeks. Researchers also obtained body weight and high-sensitivity C-reactive protein at 52 weeks, blood pressure at 48 weeks, and patient-reported sleep-related impairment and disturbance.
OSA, cardiometabolic outcomes
In the treatment-regimen estimand, tirzepatide was associated with a greater decline in AHI than placebo both in the trial for adults who did not use PAP (mean difference, –20 events per hour; 95% CI, –25.8 to –14.2; P < .001) and in the trial for adults using PAP therapy (mean difference, –23.8 events per hour; 95% CI, –29.6 to –17.9; P < .001). Of the study participants receiving tirzepatide, 42.2% of those not using PAP therapy and 50.2% of adults using PAP achieved an AHI of fewer than five events per hour or five to 14 events per hour with an Epworth Sleepiness Scale score of 10 or less at 52 weeks.
In the first trial, adults not using PAP receiving tirzepatide lost 17.7% of their body weight at 52 weeks compared with a 1.6% weight loss for placebo (P < .001). Adults using PAP and receiving tirzepatide lost 19.6% of their body weight compared with a 2.3% weight loss for placebo in the second trial (P < .001).
High-sensitivity C-reactive protein declined for those receiving tirzepatide by 40.1% for the adults not using PAP and by 48.2% for those using PAP. Both declines were greater than those observed with placebo. Among adults not using PAP, there was a 9.5 mm Hg decline in systolic BP in the tirzepatide group compared with a 1.8 mm Hg decrease for placebo (P < .001). Adults using PAP and receiving tirzepatide had a 7.6 mm Hg drop in systolic BP compared with a 3.9 mm Hg decrease for the placebo group (P < .05).
In pooled data from both trials, patient-reported sleep-related impairment and disturbance scores declined more for adults receiving tirzepatide than those in the placebo groups.
“We have a potential new treatment for OSA, which will add to our existing therapies,” Malhotra said of the findings during a press conference.
No new safety signals
Among adults not using PAP therapy, 79.8% of the tirzepatide group and 76.7% of the placebo group experienced an adverse event. For adults using PAP, adverse events were reported by 83.2% of the tirzepatide group and 72.8% of the placebo group. The most frequent adverse events were gastrointestinal in nature and were generally mild to moderate. Malhotra said the events were similar to what was observed in prior SURMOUNT trials.
“The number of patients who stopped therapy because of adverse events was very few,” Malhotra said during a press conference.
Serious adverse events occurred in 7.5% of all participants. There were two confirmed cases of acute pancreatitis among adults receiving tirzepatide. Five cases of severe or serious depressive disorder or suicidal ideation occurred, with three in the placebo group and two in the tirzepatide group. No deaths were reported in either trial.
Link between weight loss, OSA benefits
The reduction in body weight could be the major factor for improving OSA symptoms, according to Vaishnavi Kundel, MD, MS, program director of the sleep medicine fellowship and associate professor of medicine in the division of pulmonary, critical care and sleep medicine at the Icahn School of Medicine at Mount Sinai. She cited a study published in JAMA in 2000 that found a 10% weight loss was associated with an estimated 26% decrease in AHI.
“This really tells us of the need for better weight management strategies for OSA,” Kundel said during a presentation.
The reduction in AHI could be even greater than what was suggested in the JAMA article. In a systematic meta-analysis of 27 studies of bariatric, lifestyle and pharmacologic interventions for moderate to severe OSA, researchers estimated a 10% change in BMI was equivalent to a 36% reduction in AHI, and reducing BMI by 20% could lower AHI by 57%. Louis J. Aronne, MD, FACP, FTOS, DANOM, the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medical College in New York, said in SURMOUNT-OSA an 18% weight loss was associated with a 55% decline in AHI and the trial’s numbers similarly align with the findings of the meta-analysis.
“Unlike other areas where we’ve seen an independent effect of these compounds in addition to the weight-loss effect, this would suggest to me that it’s weight loss alone [contributing to OSA improvements], that there may not be an independent effect from the GLP-1 or GIP stimulation,” Aronne said during a presentation.
Aronne said continuous positive airway pressure (CPAP) therapy remains an effective treatment for OSA, but it is possible combination therapy with tirzepatide plus CPAP could be the optimal for improving OSA symptoms and lowering obesity-related cardiometabolic risk.
References:
- Malhotra A, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2404881.
- Peppard PE, et al. JAMA. 2000;doi:10.1001/jama.284.23.3015.
Perspective
Back to Top
Add yet another candidate to the expanding indications for GLP-1 receptor agonist-based agents: obstructive sleep apnea. As one of the most common entities associated with obesity, OSA is still searching for a primary approved pharmacologic treatment. While positive airway pressure (PAP) remains the gold standard treatment, adherence is not particularly favorable. Enter the GLP-1/GIP agonist tirzepatide.
This is the largest GLP-1 receptor agonist-based study evaluating the impact that treatment has on OSA. The results indicated a significant reduction in the apnea-hypopnea-index (AHI) per hour — the primary outcome — vs placebo in patients with obesity and moderate to severe OSA. They separated the subjects into groups based on whether they were using PAP therapy. The improvements in AHI and secondary outcomes, including blood pressure and levels of high-sensitivity C-reactive protein, extended to both groups. Weight loss nearing 20% from baseline was similar to other studies (Jastreboff A, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2206038) demonstrating that patients with OSA can effectively lose weight. The hs-CRP reductions may provide insights to possible mechanisms beyond pure weight loss. Evidence suggests that adipocyte inflammation may suppress central and upper airway control (Papaetis GS. Arch Med Sci Atheroscoler Dis. 2023;doi:10.5114/amsad/161170). The improvements in blood pressure, more so in the non-PAP group, are important and additional studies are needed to disentangle the relationships between improvements in OSA dynamics and key CV outcomes.
Is there an inherent incretin mechanism for these changes, or is it just a result of significant weight loss? The answers to this question may add to the ongoing discussions of incretin-based availability, health care disparities and global economics.
Additional observations based on this study include: Is this a GLP-1-based class effect, or is this unique to the dual agonist tirzepatide? While the outcomes reported in the study are important, further analysis of Epworth Sleep Score, daytime sleepiness and quality of sleep are also needed. The study also had a gross underrepresentation of Black participants. And lastly, based on previous studies indicating that weight regain occurs after stopping therapy (Aronne L, et al. JAMA. 2024;doi:10.1001/jama.2023.24945) and that half of patients started on treatment may drop out within 1 year (Do D, et al. JAMA Netw Open. 2024;doi:10.1001/jamanetworkopen.2024.13172), extended follow-up and plan for equitable coverage are required to ensure successful adaptation of these historic hormonal agents.
Collapse
Malhotra A, et al. Symposium – SURMOUNT-OSA trial results and potential role of tirzepatide in treating obesity-related obstructive sleep apnea. Presented at: American Diabetes Association Scientific Sessions; June 21-24, 2024; Orlando.
Read more about
Click Here to Manage Email Alerts