Christoph Wanner1, Silvio E Inzucchi2, Bernard Zinman3, Audrey Koitka-Weber1,4,5, Michaela Mattheus6, Jyothis T George4, Maximilian von Eynatten4, Sibylle J Hauske4,7. 1. Department of Medicine, Division of Nephrology, Wuerzburg University Clinic, Wuerzburg, Germany. 2. Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut, USA. 3. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. 4. Boehringer Ingelheim International GmbH, Ingelheim, Germany. 5. Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia. 6. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. 7. Vth Department of Medicine, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Abstract
AIM: To explore the cardiovascular (CV) and kidney effects of empagliflozin in patients with different clinical phenotypes of diabetic kidney disease (DKD) (i.e. with the presence or absence of overt albuminuria) participating in the EMPA-REG OUTCOME trial. MATERIALS AND METHODS: EMPA-REG OUTCOME randomized participants (1:1:1) to empagliflozin 10 mg, 25 mg or placebo, added to standard of care. Post hoc, patients with different clinical phenotypes of DKD at baseline were categorized in three subgroups: (a) overt DKD (overt albuminuria [urinary albumin-to-creatinine ratio of >300 mg/g] with any estimated glomerular filtration rate [eGFR]; n = 769); (b) non-overt DKD (kidney impairment [eGFR < 60 mL/min/1.73 m2 ] without overt albuminuria [urinary albumin-to-creatinine ratio of ≤300 mg/g]; n = 1290); and (c) 'all others' (eGFR ≥ 60 mL/min/1.73 m2 without overt albuminuria; n = 4893). Analyses included CV (death, hospitalization for heart failure, all-cause hospitalization) and selected kidney outcomes, change in eGFR and kidney safety. Cox proportional hazards models assessed the consistency of treatment effect across subgroups. RESULTS:Empagliflozin significantly reduced the risk of CV and kidney outcomes across all subgroups (P-values for interaction >.05), consistent with the overall trial population findings. Empagliflozin also significantly reduced the yearly loss of eGFR, assessed by chronic slopes, in all subgroups. The adverse event profile of empagliflozin was similar across all subgroups. CONCLUSIONS:Empagliflozin may improve CV and kidney outcomes and slow the progression of kidney disease in type 2 diabetes patients with DKD, irrespective of its clinical form, both with or without the presence of overt albuminuria.
RCT Entities:
AIM: To explore the cardiovascular (CV) and kidney effects of empagliflozin in patients with different clinical phenotypes of diabetic kidney disease (DKD) (i.e. with the presence or absence of overt albuminuria) participating in the EMPA-REG OUTCOME trial. MATERIALS AND METHODS: EMPA-REG OUTCOME randomized participants (1:1:1) to empagliflozin 10 mg, 25 mg or placebo, added to standard of care. Post hoc, patients with different clinical phenotypes of DKD at baseline were categorized in three subgroups: (a) overt DKD (overt albuminuria [urinary albumin-to-creatinine ratio of >300 mg/g] with any estimated glomerular filtration rate [eGFR]; n = 769); (b) non-overt DKD (kidney impairment [eGFR < 60 mL/min/1.73 m2 ] without overt albuminuria [urinary albumin-to-creatinine ratio of ≤300 mg/g]; n = 1290); and (c) 'all others' (eGFR ≥ 60 mL/min/1.73 m2 without overt albuminuria; n = 4893). Analyses included CV (death, hospitalization for heart failure, all-cause hospitalization) and selected kidney outcomes, change in eGFR and kidney safety. Cox proportional hazards models assessed the consistency of treatment effect across subgroups. RESULTS:Empagliflozin significantly reduced the risk of CV and kidney outcomes across all subgroups (P-values for interaction >.05), consistent with the overall trial population findings. Empagliflozin also significantly reduced the yearly loss of eGFR, assessed by chronic slopes, in all subgroups. The adverse event profile of empagliflozin was similar across all subgroups. CONCLUSIONS:Empagliflozin may improve CV and kidney outcomes and slow the progression of kidney disease in type 2 diabetespatients with DKD, irrespective of its clinical form, both with or without the presence of overt albuminuria.
Authors: Carlos King Ho Wong; Kristy Tsz Kwan Lau; Eric Ho Man Tang; Chi Ho Lee; Carmen Yu Yan Lee; Yu Cho Woo; Ivan Chi Ho Au; Kathryn Choon Beng Tan; David Tak Wai Lui Journal: Cardiovasc Diabetol Date: 2022-06-03 Impact factor: 8.949
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