Tirzepatide Significantly Reduces Weight in Patients with OSA

Ron Grunstein, MBBS, MD, PhD,

Credit: Linkedin

Patients with obstructive sleep apnea (OSA) and obesity or overweight status achieved potentially clinically-impactful weight reduction when receiving tirzepatide (Mounjaro) in the SURMOUNT-1 trial, according to new analysis findings presented at SLEEP 2024 this week.¹

Investigators from the Eli Lilly-sponsored trial reported new data at the SLEEP conference in Houston, TX, this weekend that which showed up to two-thirds of patients with obesity/overweight and OSA were able to achieve ≥20% weight reduction after 72 weeks with the GIP/GLP-1 receptor agonist tirzepatide. The findings provide credence to the ongoing SURMOUNT-OSA trial, which is currently aiming to assess tirzepatide in the treatment of apnea hypopnea-index (AHI) response, as well as sleep apnea-specific hypoxic burden and cardiometabolic outcomes.²

Led by Ron Grunstein, MBBS, MD, PhD, head of the Sleep and Circadian Research Group (CIRCUS) at Woolcock Institute, investigators conducted a post-hoc analysis of the SURMOUNT-1 trial to interpret efficacy of tirzepatide versus placebo on the weight reduction of participants with OSA and obesity/overweight.¹

“Obesity has been estimated to be prevalent in 70% of patients with OSA,” Grunstein and colleagues wrote. “In SURMOUNT-1, phase 3, 72-week, randomized, double-blind clinical trial in participants with obesity or overweight, those treated with tirzepatide achieved significantly greater weight reduction than placebo.”³

The team conducted a dose-response mixed models for repeatedmeasures analysis of the SURMOUNT-1 trial participants who reported a baseline medical history of either apnea, positive airway pressure therapy, or sleep apnea syndrome.¹ They assessed measures for weight loss in patients via the modified intention-to-treat analysis of those received ≥1 dose of tirzepatide 5 mg, 10 mg or 15 mg, versus placebo.

Their analysis included 197 trial participants with OSA. Among them, 41 received 5 mg tirzepatide; 51 received 10 mg, 46 received 15 mg, and 59 received placebo. Baseline ages ranged from 48 – 53 years old, with a mean body mass index of 39 – 49 kg/m2.

Mean patient body weight ranged from 110 – 122 kg. Presence of hypertension ranged from 48% – 73%, and females comprised 42% - 53% of the cohorts.

Mean percent weight changes were -11.2% among patients receiving 5 mg, -18.2% receiving 10 mg, and -20.7% receiving 20 mg versus placebo at week 72, investigators noted (P <.001).The team also reported that 83% - 98% of patients in the treatment arm achieved a ≥5% body weight reduction, versus 25% of patients receiving placebo. Another 46% - 93% of tirzepatide-treated patients achieved ≥10% body weight reduction, versus 15% of patients on placebo (P <.001).

Even more significantly, 27% - 62% of patients in the tirzepatide arms achieved a ≥20% body weight reduction at 72 weeks, versus none in the placebo group (5 mg P = .006; 10 mg and 15 mg P <.001).

Grunstein and colleagues additionally observed significantly reduced mean waist circumference from baseline to week 72 in all 3 tirzepatide arms, while placebo was not associated with a significant reduction.

With SURMOUNT-OSA underway, the team concluded the GLP-1/GIP receptor agonist tirzepatide may hold high potential in treating the risk-driving factor of obesity and overweight status in patients with OSA.

“Participants with OSA and obesity or overweight treated with tirzepatide had significantly greater weight reduction than those treated with placebo in the SURMOUNT-1 trial,” they wrote. “This degree of weight loss would be expected to have a clinically meaningful impact on OSA severity and is being investigated in the SURMOUNT-OSA trial.”

References

1. ^{Grunstein RR, Taylor R, Shinde S, Dunn JP, et al. EFFECT OF TIRZEPATIDE ON WEIGHT LOSS IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA AND OBESITY FROM SURMOUNT-1. Paper presented at: Associated Professional Sleep Societies (SLEEP) 2024 Annual Meeting. Houston, TX. June 1 – 5, 2024.}
2. ^{Malhotra A, Bednarik J, Chakladar S, et al. Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial. Contemp Clin Trials. 2024;141:107516. doi:10.1016/j.cct.2024.107516}
3. ^{Campbell P. SURMOUNT-1 Results Tout Tirzepatide's Weight Loss Benefits. HCPLive. Published April 28, 2022. https://www.hcplive.com/view/surmount-1-results-tout-tirzepatide-s-weight-loss-benefits}