SGLT2 Inhibitors for Treatment of Diabetic Nephropathy

Background: Sodium-glucose co-transporter 2 (SGLT2) are medications approved for treatment of type 2 diabetes. Recent evidence suggests that these agents exert Reno protective effects. Methods: Review of literature (English, French, Spanish) from January 1990 to November 10, 2019. Searching terms include sodium-glucose co-transporters 2 inhibitors (SGLT2) inhibitors, chronic kidney disease (CKD), end-stage kidney disease (ESKD). Randomized trials, meta-analysis, expert opinions and guidelines are also reviewed. Results: The effects of canagliflozin on renal events were evaluated in patients with type 2 diabetes and albuminuric diabetic nephropathy already on renin-angiotensin (RAS) blockade. The primary outcome was a composite of the incidence of ESKD, doubling of serum creatinine, renal or cardiovascular (CV) death. Canagliflozin was associated with 30% reduction in the incidence of this primary outcome [hazard ratio (HR) 0.70, 95% CI 0.59-0.82, P=0.00001)]. Similar results were generally reported in large CV trials of canagliflozin, empagliflozin and dapagliflozin although renal events were secondary or post-hoc outcomes. Renoprotection by SGLT2 inhibitors was observed in patients with different degrees of renal function at baseline, with or without albuminuria, and taking or not RAS blockers. SGLT2 inhibitors were generally safe with drug discontinuation rates similar to placebo. Canagliflozin was tolerated in patients with eGFR <60 ml/min/1.73 m2. The incidence of acute renal injury was numerically less frequent with SGLT2 inhibitors compared with placebo. Conclusions: SGLT2 inhibitors slow progression of diabetic nephropathy and should be standard of care on top of RAS blockers for renal protection in patients with type 2 diabetes. Regulatory authorities should consider allowing using canagliflozin 100 mg/d in patients with estimated glomerular filtration rate (eGFR) between 30-45 ml/min/1.73 m2./p>