American Diabetes Association
Neeland-OSA_and_EMPA_Diab_Care-Supplemental_Material_R1_090820.pdf (538.27 kB)

The Impact of Empagliflozin on Obstructive Sleep Apnea, Cardiovascular, and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial

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posted on 2020-10-01, 18:32 authored by Ian J. Neeland, Bjorn Eliasson, Takatoshi Kasai, Nikolaus Marx, Bernard Zinman, Silvio E. Inzucchi, Christoph Wanner, Isabella Zwiener, Brian S. Wojeck, Henry K Yaggi, Odd Erik Johansen, the EMPA-REG OUTCOME® investigators
Objective: 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.

Research Design and Methods: 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.

Results: 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]).

Conclusions: 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.


This study was sponsored by Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. Dr. Neeland is supported by grant K23 DK106520 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institute of Health and the Dedman Family Scholarship in Clinical Care from UT Southwestern.


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