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

To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes. We 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. Forty-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 m , 95% CI [-0.90 to 0.23]) or in patients with chronic kidney disease (CKD) (WMD -0.78 ml/min per 1.73 m , 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 m , 95% CI [-1.42 to -0.54]), and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m , 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]). SGLT2 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.