The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes

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Cherney , D , Lund , S S , Perkins , B A , Groop , P-H , Cooper , M E , Kaspers , S , Pfarr , E , Woerle , H J & von Eynatten , M 2016 , ' The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes ' , Diabetologia , vol. 59 , no. 9 , pp. 1860-1870 . https://doi.org/10.1007/s00125-016-4008-2

Title: The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes
Author: Cherney, David; Lund, Soren S.; Perkins, Bruce A.; Groop, Per-Henrik; Cooper, Mark E.; Kaspers, Stefan; Pfarr, Egon; Woerle, Hans J.; von Eynatten, Maximilian
Contributor organization: Clinicum
Per Henrik Groop / Principal Investigator
Department of Medicine
Diabetes and Obesity Research Program
Research Programs Unit
Nefrologian yksikkö
Date: 2016-09
Language: eng
Number of pages: 11
Belongs to series: Diabetologia
ISSN: 0012-186X
DOI: https://doi.org/10.1007/s00125-016-4008-2
URI: http://hdl.handle.net/10138/224129
Abstract: Aims/hypothesis Sodium glucose cotransporter 2 (SGLT2) inhibition lowers HbA(1c), systolic BP (SBP) and weight in patients with type 2 diabetes and reduces renal hyperfiltration associated with type 1 diabetes, suggesting decreased intraglomerular hypertension. As lowering HbA(1c), SBP, weight and intraglomerular pressure is associated with antialbuminuric effects in diabetes, we hypothesised that SGLT2 inhibition would reduce the urine albumin-to-creatinine ratio (UACR) to a clinically meaningful extent. Methods We examined the effect of the SGLT2 inhibitor empagliflozin on UACR by pooling data from patients with type 2 diabetes and prevalent microalbuminuria (UACR=30-300 mg/g; n = 636) or macroalbuminuria (UACR>300 mg/g; n=215) who participated in one of five phase III randomised clinical trials. Primary assessment was defined as percentage change in geometric mean UACR from baseline to week 24. Results After controlling for clinical confounders including baseline log-transformed UACR, HbA(1c), SBP and estimated GFR (according to the Modification of Diet in Renal Disease [MDRD] formula), treatment with empagliflozin significantly reduced UACR in patients with microalbuminuria (-32% vs placebo; p Conclusions/interpretation In patients with type 2 diabetes and either micro-or macroalbuminuria, empagliflozin reduced UACR by a clinically meaningful amount. This effect was largely independent of the known metabolic or systemic haemodynamic effects of this drug class. Our results further support a direct renal effect of SGLT2 inhibitors. Prospective studies are needed to explore the potential of this intervention to alter the course of kidney disease in high-risk patients with diabetes. Trial registration: Clinicaltrials.gov NCT01177813 (study 1); NCT01159600 (study 2); NCT01159600 (study 3); NCT01210001 (study 4); and NCT01164501 (study 5).
Subject: Empagliflozin
Macroalbuminuria
Microalbuminuria
Sodium glucose cotransporter 2
Type 2 diabetes
Urine albumin-to-creatinine ratio
PLACEBO-CONTROLLED TRIAL
CHRONIC KIDNEY-DISEASE
DOUBLE-BLIND
SGLT2 INHIBITOR
LONG-TERM
ADD-ON
DIETARY-SODIUM
ALBUMINURIA
RATS
HYPERFILTRATION
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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