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The effect of SGLT-2 inhibitors on albuminuria and proteinuria in diabetes mellitus

a systematic review and meta-analysis of randomized controlled trials

Piperidou, Alexiaa; Sarafidis, Pantelisb; Boutou, Afroditic; Thomopoulos, Costasd; Loutradis, Charalamposb; Alexandrou, Maria Elenie; Tsapas, Apostolosf; Karagiannis, Asteriosa

doi: 10.1097/HJH.0000000000002050

Diabetic kidney disease is a serious microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease in western countries. New therapeutic agents are needed to delay its onset and progression. Recent literature suggests that sodium-glucose cotransporter 2 (SGLT-2) inhibitors may have renoprotective effects. Our aim was to systematically review the effect of SGLT-2 inhibitors on albuminuria and proteinuria in patients with diabetes mellitus. Studies were identified by search in major electronic databases, clinical trial registers, and sources of gray literature. We included randomized controlled trials of currently approved SGLT-2 inhibitors with a duration of at least 12 weeks. The primary outcome was the between-groups difference in the proportional (%) change of albuminuria or proteinuria between baseline and end of treatment. SGLT-2 inhibitors were associated with statistically significant reduction in albuminuria compared to placebo or active control [weighted mean difference (WMD) −25.39%, 95% confidence interval (CI) −34.17 to −16.62] (15 studies, N = 17 540 patients). When trials were stratified according to the level of baseline albuminuria, reduction in urine albumin-to-creatinine ratio was more prominent in randomized controlled trials in patients with moderately (WMD −40.78%, 95% CI −63.21 to −18.34) or severely increased albuminuria (WMD −36.40%, 95% CI −51.53 to −21.26). Only one study reported data for urine protein-to-creatinine ratio. Finally, SGLT-2 inhibitors reduced systolic and diastolic blood pressure by 4.43 mmHg (95% CI −5.24 to −3.63) and 1.81 mmHg (95% CI −2.38 to −1.23), respectively.

a2nd Propedeutic Department of Internal Medicine

bDepartment of Nephrology, Aristotle University of Thessaloniki, Hippokration General Hospital

cDepartment of Respiratory Medicine, Papanikolaou Hospital, Thessaloniki

dDepartment of Cardiology, Helena Venizelou Hospital, Athens

eDepartment of Nephrology, Papageorgiou Hospital

fClinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

Correspondence to Pantelis Sarafidis, MD, MSc, PhD, Assistant Professor in Nephrology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. E-mail:

Abbreviations: ADA, American Diabetes Association; AKI, acute kidney injury; BP, blood pressure; CI, confidence interval; DBP, diastolic blood pressure; DKD, diabetic kidney disease; EASD, European Association for the Study of Diabetes; eGFR, estimated glomerular filtration ratio; ESRD, end-stage renal disease; Hct, hematocrit; IQR, interquartile range; MESH, Medical Subject Headings; RAAS, renin-angiotensin-aldosterone system; RCT, randomized clinical trial; RoB, risk of bias; SBP, systolic blood pressure; SD, standard deviation; SE, standard error; SGLT-2, sodium-glucose cotransporter 2; TGF, tubular-glomerular feedback; UACR, urine albumin-to-creatinine ratio; UAE, urine albumin excretion; UPCR, urine protein-to-creatinine ratio; UPE, urine protein excretion; WHO, World Health Organization; WMD, weighted mean difference

Received 26 October, 2018

Revised 5 December, 2018

Accepted 28 December, 2018

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