Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis.

Lubin Xu,Li Wang,Xinyu Zhao,Peng Xia,Limeng Chen,Yang Li,Jiaxin Lang,Yang Yu

doi:10.7717/peerj.3405

Abstract

AimTo evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes.MethodsWe conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR) changes. Data were synthesized using the random-effects model.ResultsForty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD), −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23]) or in patients with chronic kidney disease (CKD) (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]). SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54]), and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]). Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06]), but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]).ConclusionsSGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

Highlights

With increasing incidence and prevalence of diabetes mellitus, diabetic nephropathy has become the leading cause of end-stage renal disease (ESRD), accounting for 50% of cases in the developed world (Tuttle et al, 2014; Wild et al, 2004)
We included RCTs conducted on adult type 2 diabetic patients that compared Sodium-glucose co-transporter 2 (SGLT2) inhibitors with either placebo or other antidiabetic drugs and reported changes in estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR)
In this systematic review and meta-analysis, we identified no significant effect of SGLT2 inhibition on eGFR either in type 2 diabetic patients in general or in type 2 diabetic patients with chronic kidney disease (CKD)

Summary

Introduction

With increasing incidence and prevalence of diabetes mellitus, diabetic nephropathy has become the leading cause of end-stage renal disease (ESRD), accounting for 50% of cases in the developed world (Tuttle et al, 2014; Wild et al, 2004). Current management of diabetic nephropathy includes avoidance of nephrotoxic agents, prevention of infections, glycemic control, and blood pressure control, with emphasis on the use of renin-angiotensinaldosterone system (RAAS) inhibitors. These strategies only provide partial renoprotection against progression of diabetic nephropathy (Bilous et al, 2009; Lewis et al, 1993; Lewis et al, 2001; Mauer et al, 2009). In addition to glycemic control, SGLT2 inhibitors lower blood pressure, control body weight, and reduce cardiovascular mortality in type 2 diabetic patients with high cardiovascular risk (Baker et al, 2014; Matthaei et al, 2015; Tikkanen et al, 2015; Wilding et al, 2015; Zinman et al, 2015b)

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