Canagliflozin, a new sodium-glucose cotransporter 2 inhibitor, in the treatment of diabetes.
OBJECTIVE
The published evidence on the pharmacology, pharmacodynamics, pharmacokinetics, safety, and efficacy of a promising investigational agent for managing type 2 diabetes is evaluated.


CONCLUSIONS
Canagliflozin belongs to a class of agents-the sodium-glucose co-transporter 2 (SGLT2) inhibitors-whose novel mechanism of action offers potential advantages over other antihyperglycemic agents, including a relatively low hypoglycemia risk and weight loss-promoting effects. Canagliflozin has dose-dependent pharmacokinetics, and research in laboratory animals demonstrated high oral bioavailability (85%) and rapid effects in lowering glycosylated hemoglobin (HbA(1c)) values. In four early-stage clinical trials involving a total of over 500 patients, the use of canagliflozin for varying periods was associated with significant mean reductions in HbA(1c) (absolute reductions of 0.45-0.92%) and fasting plasma glucose (decreases ranged from 16.2% to 42.4%) and weight loss ranging from 0.7 to 3.5 kg. More than a dozen Phase II or III clinical trials of canagliflozin in adults are ongoing or were recently completed, but the final results of most of those studies have not been published. Adverse effects reported in clinical trials of canagliflozin include urinary tract and genital infections, occurring in about 10% of patients. Additional and larger Phase III clinical trials to delineate the potential role of canagliflozin and other SGLT2 inhibitors in the management of diabetes (including studies involving the elderly, children, and patients with renal or hepatic dysfunction) are planned or currently underway.


CONCLUSIONS
Canagliflozin and other investigational SGLT2 inhibitors have a novel mechanism of action that may offer a future alternative treatment pathway for managing type 2 diabetes.
Department of Pharmacy Practice, College of Pharmacy and Health Sciences (COPHS), Butler University, Indianapolis, IN, USA. snisly@iuhealth.org
Sarah A
SA
Nisly
Denise M
DM
Kolanczyk
Alison M
AM
Walton
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D000068896:Canagliflozin; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D000068896:Canagliflozin; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C089180:SLC5A2 protein, human