OSA is a common sleep disorder marked by recurrent upper airway obstruction during sleep, causing apneas or hypopneas.^1,2 These episodes lead to oxygen desaturation, sleep fragmentation, and increased cardiovascular risks, such as hypertension, stroke, and heart failure.^1,3 Excess adiposity is a significant reversible risk factor for OSA, contributing to airway obstruction and respiratory dysfunction.¹ Adherence to PAP therapy is often challenging, as many patients find it cumbersome or intolerable, highlighting the need for effective pharmacological alternatives.^1,2

Tirzepatide is a dual GIP and GLP-1 receptor agonist that activates receptors for incretin hormones, which play key roles in glucose metabolism and appetite regulation.⁴ By reducing appetite and food intake, tirzepatide promotes effective weight loss, a key factor in improving OSA symptoms.⁴ Tirzepatide’s dual mechanism of action enhances its efficacy in weight reduction and metabolic regulation, making it a promising option for patients with OSA and obesity.²

In SURMOUNT-OSA, a phase 3, double-blind, randomized, controlled trial, adults (n=469) with moderate-to-severe OSA and obesity were randomized 1:1 to receive either tirzepatide (10mg or 15mg) or placebo once weekly for 52 weeks, alongside lifestyle interventions in trial 1 (patients not receiving treatment with PAP at baseline; 234 participants) and trial 2 (patients receiving PAP at baseline; 235 participants).^1,2

The primary endpoint was the change in the Apnea-Hypopnea Index (AHI) from baseline.^1,2 In trial 1, participants had a baseline AHI of 51.5 events per hour, with a mean BMI of 39.1.^1,2 After 52 weeks, tirzepatide led to a mean AHI change of -25.3 events per hour (95% CI: -29.3 to -21.2), compared to -5.3 events per hour (95% CI: -9.4 to -1.1) with placebo, resulting in an estimated treatment difference of -20.0 events per hour (95% CI: -25.8 to -14.2; p<0.001).¹ These findings confirm tirzepatide’s efficacy in significantly reducing OSA severity in individuals not using PAP therapy.¹ In trial 2, participants had a baseline AHI of 49.5 events per hour and a mean BMI of 38.7.¹ After 52 weeks, tirzepatide led to a mean AHI change of -29.3 events per hour (95% CI: -33.2 to -25.4), compared to 5.5 events per hour (95% CI: -9.9 to -1.2) with placebo, yielding an estimated treatment difference of -23.8 events per hour (95% CI: -29.6 to -17.9; p<0.001).¹ These results suggest that tirzepatide may serve as an effective adjunctive therapy to PAP, further improving sleep apnea outcomes in patients who remain on standard OSA treatment.¹ Body weight reductions were also notable, with a mean decrease of -17.7% (95% CI: -19.0 to -16.3; p<0.001) in trial 1 and -19.6% (95% CI: -21.0 to -18.2; p<0.001) in trial 2, reinforcing the drug’s role in obesity management.¹

In terms of safety, adverse events were reported in 79.8% of tirzepatide and 76.7% of placebo recipients in trial 1, and 83.2% and 72.8%, respectively, in trial 2.¹ Most were mild-to-moderate gastrointestinal events, primarily during dose escalation.¹ Serious adverse events were similar between groups, with no cases of medullary thyroid cancer and two cases of acute pancreatitis in trial 2.¹ No deaths occurred, and the safety profile aligned with previous findings.¹

In summary, tirzepatide significantly improved AHI compared to placebo in obese patients.¹ Its safety profile was consistent with that observed in previous studies, offering a promising new strategy for patients with OSA and obesity.¹