Renal effects of canagliflozin in type 2 diabetes mellitus.
BACKGROUND
Chronic kidney disease is commonly associated with type 2 diabetes mellitus (T2DM) and may impact the efficacy and safety of glucose-lowering therapies. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces blood glucose levels in patients with T2DM by lowering the renal threshold for glucose, thereby promoting urinary glucose excretion. This review describes the pharmacology, efficacy and safety of canagliflozin according to kidney function in participants with T2DM.


METHODS
Published articles that reported efficacy, safety and pharmacokinetics/pharmacodynamics data for canagliflozin in patients with T2DM and impaired renal function, and renal safety data with canagliflozin in various populations of patients with T2DM through May 2015 were included.


RESULTS
Early transient reductions in estimated glomerular filtration rate were observed with canagliflozin; these changes generally stabilized or attenuated over time and reversed after discontinuation, suggesting no renal (glomerular or tubular) damage with canagliflozin treatment. Urinary albumin-to-creatinine ratios were reduced with canagliflozin. Canagliflozin was generally well tolerated in patients with normal or mild to moderately impaired renal function, with a modestly higher incidence of renal-related adverse events and volume depletion-related adverse events in patients with moderate renal impairment. Adverse events related to potassium elevations were infrequent with canagliflozin 100 mg regardless of kidney function status; however, patients with moderately impaired kidney function experienced hyperkalemia more frequently with canagliflozin 300 mg compared with patients treated with either canagliflozin 100 mg or placebo. Canagliflozin was not associated with increased cardiovascular risk across studies; however, relatively few events among patients with impaired renal function meant that the analysis was not adequately powered to examine this outcome, and results from separate trials are awaited.


CONCLUSIONS
Overall, canagliflozin is associated with small, transient changes in kidney function, and is well tolerated in patients with T2DM with varying kidney function status.
a a George Institute for Global Health, University of Sydney , Sydney , NSW , Australia.
Vlado
V
Perkovic
a a George Institute for Global Health, University of Sydney , Sydney , NSW , Australia.
Meg
M
Jardine
b b Janssen Research & Development, LLC , Raritan , NJ , USA.
Ujjwala
U
Vijapurkar
b b Janssen Research & Development, LLC , Raritan , NJ , USA.
Gary
G
Meininger
D000068896:Canagliflozin / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D007677:Kidney Function Tests; D051437:Renal Insufficiency / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin
Canagliflozin; Chronic kidney disease; Kidney; Safety; Type 2 diabetes mellitus