Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial

Abstract

Purpose The sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin may reduce the incidence of obstructive sleep apnea (OSA) in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. This analysis of VERTIS CV, the CV outcome trial for the SGLT2i ertugliflozin conducted in a similar group of patients, explored the effects of ertugliflozin on reported incident OSA. Methods In VERTIS CV, patients ≥ 40 years with T2D and atherosclerotic CV disease (ASCVD) were randomized to ertugliflozin 5 or 15 mg or placebo. The primary endpoint was the composite of major adverse CV events. This exploratory analysis evaluated the impact of ertugliflozin (5 and 15 mg pooled) on incident OSA. Patients with prevalent OSA were excluded. Incident OSA events were based on investigator-reported events using the MedDRA SMQ term “sleep apnea syndrome.” A multivariable Cox proportional hazards regression model was constructed to assess the association between ertugliflozin and incident OSA. Results Of 8246 patients enrolled, 7697 (93.3%) were without baseline OSA (placebo, n = 2561; ertugliflozin, n = 5136; mean age 64.4 years; BMI 31.7 kg/m2; HbA1c, 8.2%; 69.2% male; 88.3% White). The OSA incidence rate was 1.44 per 1000 person-years versus 2.61 per 1000 person-years among patients treated with ertugliflozin versus placebo, respectively, corresponding to a 48% relative risk reduction (HR 0.52; 95% CI 0.28–0.96; P = 0.04). Conclusions In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to the literature that SGLT2is may have a significant beneficial impact on OSA. Trial registration. ClinicalTrials.gov identifier: NCT01986881.

Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

“…SGLT2i have been shown to reduce incident obstructive sleep apnea in two SGLT2i CVOTs based on adverse event reporting (304,305). However, it is not clear that the data collected on incident obstructive sleep apnea in these trials were complete or that the benefit is mediated through changes in weight.…”

GLP-1 receptor agonists, SGLT-2 inhibitors, and obstructive sleep apnoea: can new allies face an old enemy?

“…An exploratory analysis showed that approximately 7% of the population enrolled experienced baseline OSA. Among patients without baseline OSA, there was a 48% reduction for incident OSA in those treated with ERTU versus placebo (p = 0.04) [102]. There was an early differentiation in the incidence of OSA (from the first 12 months of the study) between patients treated with ERTU versus placebo.…”

Metabolic Crossroads: Unveiling the Complex Interactions between Obstructive Sleep Apnoea and Metabolic Syndrome

“…For instance, the SURMOUNT-OSA (NCT05412004) study, a 52-week, phase III randomised controlled trial, is underway to explore the efficacy and safety of tirzepatide (a GLP-2 and GIP receptor agonist) in the treatment of OSA. Similarly, sodium-glucose co-transporter-2 inhibitors (SGLT2is), a group of medications that has been shown to offer major cardio and renoprotective effects in recent trials, have also demonstrated encouraging results in OSA [ 142 , 143 , 144 ]. Putative mechanisms include weight reduction, reduced systemic fluid retention, nocturia-mediated suppression for the duration of REM sleep, suppression of circadian SNS activation, reduced CO 2 production and modulation of arousal threshold [ 145 , 146 , 147 , 148 ].…”