Ian J Neeland1, Bjorn Eliasson2, Takatoshi Kasai3, Nikolaus Marx4, Bernard Zinman5, Silvio E Inzucchi6, Christoph Wanner7, Isabella Zwiener8, Brian S Wojeck6, Henry K Yaggi9, Odd Erik Johansen. 1. University Hospitals Harrington Heart and Vascular Institute and Case Western Reserve University School of Medicine, Cleveland, OH ian.neeland@uhhospitals.org. 2. Department of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. 3. Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. 4. Department of Internal Medicine I (Cardiology), RWTH University Hospital, Aachen, Germany. 5. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. 6. Section of Endocrinology, Yale School of Medicine, Yale University, New Haven, CT. 7. Department of Medicine, Wuerzburg University Clinic, Wuerzburg, Germany. 8. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. 9. Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, Yale University, New Haven, CT.
Abstract
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 CV disease were randomized to empagliflozin (10 and 25 mg) or placebo daily in addition to standard of care. OSA was assessed by investigator report using Medical Dictionary for Regulatory Activities version 18.0, and CV outcomes were independently adjudicated. Analyses were performed using multivariable-adjusted Cox regression models. RESULTS: OSA was reported in 391 of 7,020 (5.6%) participants at baseline. Those with OSA were more likely to be male (83% vs. 71%) and to have moderate to severe obesity (BMI ≥35 kg/m2; 55% vs. 18%). Over a median of 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 vs. no OSA -2.9 ± 0.5 vs. -1.9 ± 0.1 kg). Incidence of 3-point major adverse CV events, CV death, heart failure hospitalization, and incident or worsening nephropathy in the placebo group was 1.2- to 2.0-fold higher for those with baseline OSA compared with 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 (hazard ratio 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.
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 CV disease were randomized to empagliflozin (10 and 25 mg) or placebo daily in addition to standard of care. OSA was assessed by investigator report using Medical Dictionary for Regulatory Activities version 18.0, and CV outcomes were independently adjudicated. Analyses were performed using multivariable-adjusted Cox regression models. RESULTS: OSA was reported in 391 of 7,020 (5.6%) participants at baseline. Those with OSA were more likely to be male (83% vs. 71%) and to have moderate to severe obesity (BMI ≥35 kg/m2; 55% vs. 18%). Over a median of 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 vs. no OSA -2.9 ± 0.5 vs. -1.9 ± 0.1 kg). Incidence of 3-point major adverse CV events, CV death, heart failure hospitalization, and incident or worsening nephropathy in the placebo group was 1.2- to 2.0-fold higher for those with baseline OSA compared with 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 (hazard ratio 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.
Authors: David W Hudgel; Sanjay R Patel; Amy M Ahasic; Susan J Bartlett; Daniel H Bessesen; Melisa A Coaker; P Michelle Fiander; Ronald R Grunstein; Indira Gurubhagavatula; Vishesh K Kapur; Christopher J Lettieri; Matthew T Naughton; Robert L Owens; Jean-Louis Pepin; Henri Tuomilehto; Kevin C Wilson Journal: Am J Respir Crit Care Med Date: 2018-09-15 Impact factor: 21.405
Authors: H Klar Yaggi; John Concato; Walter N Kernan; Judith H Lichtman; Lawrence M Brass; Vahid Mohsenin Journal: N Engl J Med Date: 2005-11-10 Impact factor: 91.245
Authors: Daniel E Jonas; Halle R Amick; Cynthia Feltner; Rachel Palmieri Weber; Marina Arvanitis; Alexander Stine; Linda Lux; Russell P Harris Journal: JAMA Date: 2017-01-24 Impact factor: 56.272
Authors: Paul E Peppard; Terry Young; Jodi H Barnet; Mari Palta; Erika W Hagen; Khin Mae Hla Journal: Am J Epidemiol Date: 2013-04-14 Impact factor: 4.897
Authors: Natalia de Albuquerque Rocha; Ian J Neeland; Peter A McCullough; Robert D Toto; Darren K McGuire Journal: Diab Vasc Dis Res Date: 2018-07-02 Impact factor: 3.291
Authors: Ian J Neeland; Darren K McGuire; Robert Chilton; Susanne Crowe; Søren S Lund; Hans J Woerle; Uli C Broedl; Odd Erik Johansen Journal: Diab Vasc Dis Res Date: 2016-03 Impact factor: 3.291
Authors: Cem Tanriover; Duygu Ucku; Merve Akyol; Enes Cevik; Asiye Kanbay; Vikas S Sridhar; David Z I Cherney; Mehmet Kanbay Journal: Sleep Breath Date: 2022-04-04 Impact factor: 2.816
Authors: Melanie J Davies; Vanita R Aroda; Billy S Collins; Robert A Gabbay; Jennifer Green; Nisa M Maruthur; Sylvia E Rosas; Stefano Del Prato; Chantal Mathieu; Geltrude Mingrone; Peter Rossing; Tsvetalina Tankova; Apostolos Tsapas; John B Buse Journal: Diabetologia Date: 2022-09-24 Impact factor: 10.460
Authors: Winfried Randerath; Jan de Lange; Jan Hedner; Jean Pierre T F Ho; Marie Marklund; Sofia Schiza; Jörg Steier; Johan Verbraecken Journal: ERJ Open Res Date: 2022-06-27
Authors: Francesco Gambino; Marta Maria Zammuto; Alessandro Virzì; Giosafat Conti; Maria Rosaria Bonsignore Journal: Intern Emerg Med Date: 2022-04-23 Impact factor: 5.472