Effects Of Sodium-Glucose Cotransporter-2 Inhibitors On Renal Events In Patients With Type 2 Diabetes: A Systematic Review And Meta-Analysis

Objective: To assess effects of sodium-glucose cotransporter2(SGLT2)inhibitors on renal events in patients with type 2 diabetes(T2DM).Methods: We conducted a systematic review and meta-analysis of randomized controlled trials(RCTs)of SGLT2 inhibitors comparing any SGLT2 inhibitors with placebo or other antidiabetic agents.We systematically searched Pub Med,Embase,Medline,OVID,Cochrane Library,Web of Science,clinicaltrials.gov and FDA web site from inception to January 6,2017.We selected the RCTs according to the inclusion criterion,then objectively appraised them by Cochrane handbook.All outcomes were pooled by the Rev Man5.3 software of Cochrane Collaboratio.Results: 38 RCTs were selected for the meta-analysis(N=20163 participants).Decreased e GFR and increased serum creatinine were observed in patients treated with the high dose of SGLT2 inhibitors for duration ≤26 weeks compared with placebo(e GFR: weighted mean difference(WMD)-0.93;95% CI-1.56 to-0.31,P=0.004;I~2=33%;serum creatinine: WMD 0.70;95%CI 0.09 to 1.30,P=0.02;I~2=0%).Pooling the data showed no significant differences between SGLT2 inhibitors and active comparators in e GFR and serum creatinine with both doses for duration ≤26 weeks(P>0.05 for each group).However,for duration ≥48 weeks,(1)There were no significant differences between SGLT2 inhibitors and placebo in e GFR and Serum creatinine with both doses(P>0.05 for each group).(2)Both doses of SGLT2 inhibitors increased e GFR and decreased Serum creatinine compared with active comparators(P>0.05 for each group).In urinary albumin to creatinine ratio(UACR),No significant differences were seen between SGLT2 inhibitors and placebo in both dose groups with two durations(P>0.05 for each group).Compared with active comparators,the high dose group treated with SGLT2 inhibitors for ≥48 weeks was associated with significant reduction in UACR(WMD-20.05;95% CI-37.79 to-2.32,P=0.03;I~2=0%).In terms of renal impairment and acute renal failure,there were no significant differences between SGLT2 inhibitors and control groups in both doses with the two durations(P>0.05 for each group).Conclusions: SGLT2 inhibitors may reduce the progression of kidney disease in patients with type 2 diabetes.