Canagliflozin is a newly approved drug for the treatment of type 2 diabetes. This agent lowers blood glucose
mainly by increasing urinary glucose excretion through inhibition of sodium glucose co-transporter 2 (SGLT2) in the
kidneys. Data derived from randomized clinical trials lasting up to 52 weeks suggest that canagliflozin is generally well
tolerated. The most common adverse effects are genital mycotic infections occurring in 11-15% of women exposed to
canagliflozin versus 2-4% of those randomized to glimepiride or sitagliptin. In men, corresponding proportions are 8-9%
versus 0.5-1%. Urinary tract infections (UTI) are slightly increased (5-7%) with the use of canagliflozin compared with
placebo (4%). The risk of hypoglycemia associated with canagliflozin is marginally higher than placebo, but markedly
increases when the drug is used in conjunction of insulin or sulfonylureas (SU), in patients with chronic kidney disease
(CKD), and in the elderly. Worsening renal function and hyperkalemia may occur in patients using canagliflozin,
particularly in patients with underlying CKD. Mild weight loss (mean 2-4 kg) and lowering of blood pressure represent 2
advantages of canagliflozin owing to its osmotic diuretic effect. However, the latter action may lead to postural
hypotension and dizziness in susceptible subjects. Another concerning adverse effect of canagliflozin is an average 8%
increase in plasma levels of low-density lipoprotein cholesterol (LDL-C) compared with placebo. Overall, canagliflozin is
a useful addition for treatment of type 2 diabetes, but its safety needs to be established in long-term clinical trials.
Canagliflozin, dapagliflozin, genital infection, safety, type 2 diabetes.
Endocrinology Division, OliveView-UCLA Medical Center, 14445 Olive View Dr, Sylmar, CA 91342, Clinical Professor of Medicine, David-Geffen Medical School, CA, USA.