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<b>Objective: </b>To explore the effects of empagliflozin on the incidence of obstructive sleep apnea (OSA) and its effects on metabolic, cardiovascular (CV), and renal outcomes among participants with or without OSA in the EMPA-REG OUTCOME trial. <p><b>Research Design and Methods: </b>Participants with diabetes and CVD were randomized to empagliflozin (10/25mg), or placebo daily in addition to standard of care. OSA was assessed by investigator-reports using MedDRA-18.0 and CV outcomes were independently adjudicated. Analyses were performed using multivariable-adjusted Cox regression models.</p> <p><b>Results: </b>OSA was reported in 391/7020 (5.6%) at baseline. Those with OSA were more likely to be male (83 vs 71%) and have moderate-severe obesity (BMI ≥35 kg/m²; 55 vs 18%). Over a median 3.1 years, empagliflozin had similar placebo-adjusted reductions in HbA1c, waist circumference, and systolic blood pressure regardless of OSA status, but a larger effect on weight (adjusted mean±SE difference at week 52: OSA/no OSA: -2.9±0.5/-1.9±0.1 kg). Incidence of 3P-MACE, CV death, heart failure hospitalization, and incident or worsening nephropathy in the placebo-group was 1.2-2.0 fold higher for those with baseline OSA compared to those without. Empagliflozin significantly reduced the risk for outcomes regardless of OSA status (p-interaction all >0.05). Fifty patients reported a new diagnosis of OSA through 7 days after medication discontinuation and this occurred less often with empagliflozin treatment (HR 0.48 [95% CI 0.27, 0.83]). </p> <p><b>Conclusions: </b>In EMPA-REG OUTCOME, participants with OSA had greater comorbidity and higher frequency of CV and renal events. Empagliflozin had favorable effects on risk factors and CV and renal outcomes regardless of preexisting OSA and may also reduce the risk for new-onset OSA.<b></b></p>

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.

<b>Objective: </b>To explore the effects of empagliflozin on the incidence of obstructive sleep apnea (OSA) and its effects on metabolic, cardiovascular (CV), and renal outcomes among participants with or without OSA in the EMPA-REG OUTCOME trial. <p><b>Research Design and Methods: </b>Participants with diabetes and CVD were randomized to empagliflozin (10/25mg), or placebo daily in addition to standard of care. OSA was assessed by investigator-reports using MedDRA-18.0 and CV outcomes were independently adjudicated. Analyses were performed using multivariable-adjusted Cox regression models.</p> <p><b>Results: </b>OSA was reported in 391/7020 (5.6%) at baseline. Those with OSA were more likely to be male (83 vs 71%) and have moderate-severe obesity (BMI ≥35 kg/m²; 55 vs 18%). Over a median 3.1 years, empagliflozin had similar placebo-adjusted reductions in HbA1c, waist circumference, and systolic blood pressure regardless of OSA status, but a larger effect on weight (adjusted mean±SE difference at week 52: OSA/no OSA: -2.9±0.5/-1.9±0.1 kg). Incidence of 3P-MACE, CV death, heart failure hospitalization, and incident or worsening nephropathy in the placebo-group was 1.2-2.0 fold higher for those with baseline OSA compared to those without. Empagliflozin significantly reduced the risk for outcomes regardless of OSA status (p-interaction all >0.05). Fifty patients reported a new diagnosis of OSA through 7 days after medication discontinuation and this occurred less often with empagliflozin treatment (HR 0.48 [95% CI 0.27, 0.83]). </p> <p><b>Conclusions: </b>In EMPA-REG OUTCOME, participants with OSA had greater comorbidity and higher frequency of CV and renal events. Empagliflozin had favorable effects on risk factors and CV and renal outcomes regardless of preexisting OSA and may also reduce the risk for new-onset OSA.<b></b></p>

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