OBJECTIVE: To examine the effects of canagliflozin, a sodium glucose 
co-transporter 2 inhibitor that lowers blood glucose by increasing urinary 
glucose excretion (UGE), on asymptomatic bacteriuria and urinary tract 
infections (UTIs).
RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, 
multicenter, dose-ranging phase 2 study, subjects with type 2 diabetes with 
inadequate glycemic control while receiving metformin were enrolled and 
randomized to one of seven arms - placebo; canagliflozin doses 50 mg, 100 mg, 
200 mg, 300 mg daily, or 300 mg twice daily; and sitagliptin 100 mg daily - for 
12 weeks.
CLINICAL TRIAL REGISTRATION: This study is registered under Clinicaltrials.gov 
identification number NCT00642278.
RESULTS: Canagliflozin increased renal glucose excretion by 35.4-61.6 mg/mg 
creatinine in the five dose groups. In the placebo group renal glucose excretion 
was increased by 1.9 mg/mg creatinine, and in the sitagliptin group it decreased 
by 1.9 mg/mg creatinine. Asymptomatic bacteriuria (ASB) were present in 6.4% of 
canagliflozin and 6.5% of placebo/sitagliptin (control) subjects at 
randomization and, at 12 weeks, in 7.7% and 6.3% of subjects, respectively (odds 
ratio [OR] 1.23; 95% confidence interval [CI], 0.45-3.89). For subjects with 
initially negative urine cultures at baseline, 3 out of 82 (3.7%) who received 
controls and 10 out of 207 (4.8%) who received canagliflozin developed 
bacteriuria (p = 0.76) at week 12. There were 21 adverse event (AE) reports of 
UTI; 16 (5.0%) in canagliflozin subjects and 5 (3.8%) in control subjects (OR 
1.31; 95% CI, 0.45-4.68).
CONCLUSIONS: In this trial, when compared with control subjects, canagliflozin 
increased UGE but was not associated with increased bacteriuria or AE reports of 
UTI. However, further studies enrolling larger numbers of subjects with longer 
term exposure to canagliflozin will be necessary to more fully understand the 
impact of this agent on the risk of developing UTI.