title: 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 m2per year (95% confidence interval [95% CI], 2.8 to 3.8), 0.5 ml/min per 1.73 m2per year (95% CI, 0.0 to 1.0), and 0.9 ml/min per 1.73 m2per 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.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; h.j.lambers.heerspink@umcg.nl.
authors.forename: Hiddo J L
authors.initials: HJ
authors.lastname: Heerspink
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey; and.
authors.forename: Mehul
authors.initials: M
authors.lastname: Desai
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Meg
authors.initials: M
authors.lastname: Jardine
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey; and.
authors.forename: Dainius
authors.initials: D
authors.lastname: Balis
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey; and.
authors.forename: Gary
authors.initials: G
authors.lastname: Meininger
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
mesh_terms: D000419:Albuminuria / Q000209:etiology* / Q000517:prevention & control*; D000068896:Canagliflozin / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000517:prevention & control*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013453:Sulfonylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013453:Sulfonylurea Compounds; D000068896:Canagliflozin; C057619:glimepiride
keywords: SGLT2; canagliflozin; diabetic nephropathy; renal function