Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects

Abstract

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 3.3 ml/min per 1.73 m² per year (95% confidence interval [95% CI], 2.8 to 3.8), 0.5 ml/min per 1.73 m² per year (95% CI, 0.0 to 1.0), and 0.9 ml/min per 1.73 m² per year (95% CI, 0.4 to 1.4), respectively (P<0.01 for each canagliflozin group 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.

Keywords: SGLT2; canagliflozin; diabetic nephropathy; renal function.

Figure 1.

Canagliflozin slows the progression of eGFR decline in patients with type 2 diabetes compared with glimepiride. (A) Changes in eGFR in the canagliflozin and glimepiride treatment arms in the overall population, and the rate of eGFR decline per year. (B) Changes in eGFR in the canagliflozin and glimepiride treatment arms in patients with U_ACR≥30 mg/g, and the rate of eGFR decline per year in patients with U_ACR≥30 mg/g.

Figure 2.

eGFR decline >30% or >40% was generally less frequent with canagliflozin compared with glimepiride.

Figure 3.

Canagliflozin decreases albuminuria compared with glimepiride. (A) Changes in U_ACR in the canagliflozin and glimepiride treatment arms in the overall population. (B) Changes in U_ACR in the canagliflozin and glimepiride treatment arms in a subgroup of patients with U_ACR≥30 mg/g at baseline.