Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin and randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6-8 mg. End points were annual change in eGFR and albuminuria over 2 years of follow-up. Glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups had eGFR declines of 3. versus glimepiride). In the subgroup of patients with baseline urinary albumin-to-creatinine ratio $30 mg/g, urinary albumin-to-creatinine ratio decreased more with canagliflozin 100 mg (31.7%; 95% CI, 8.6% to 48.9%; P=0.01) or canagliflozin 300 mg (49.3%; 95% CI, 31.9% to 62.2%; P,0.001) than with glimepiride. Patients receiving glimepiride, canagliflozin 100 mg, or canagliflozin 300 mg had reductions in HbA1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year and 0.55%, 0.65%, and 0.74%, respectively, at 2 years. In conclusion, canagliflozin 100 or 300 mg/d, compared with glimepiride, slowed the progression of renal disease over 2 years in patients with type 2 diabetes, and canagliflozin may confer renoprotective effects independently of its glycemic effects. 28: 368-375, 201728: 368-375, . doi: 10.1681 Many patients with type 2 diabetes present with hyperglycemia, hypertension, and excess weight, and develop increased albuminuria, all of which increase the risk of micro-and macrovascular complications. Current practice guidelines recommend targeting these risk factors with a range of different drugs. 1 However, despite the many drugs used, many patients do not reach treatment targets and develop potentially preventable micro-and macrovascular complications. Emerging interest in the role of the kidney in glucose homeostasis has led to the development of sodium-glucose cotransporter inhibitors. 2 These drugs are designed to inhibit sodium-glucose cotransporter 2 (SGLT2), which is located in the S1 segment of the proximal tubule. Previous phase 2 and phase 3 studies have shown that administration of SGLT2 inhibitors augments urinary glucose and sodium excretion and decreases glycated hemoglobin A1c (HbA1c), body weight, and BP in patients with type 2 diabetes. 3,4 Moreover, reductions in albuminuria have been observed after administration of SGLT2 inhibitors. 5,6
J Am Soc Nephrol