Effect of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on bacteriuria and urinary tract infection in subjects with type 2 diabetes enrolled in a 12-week, phase 2 study

Abstract

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:

ClinicalTrials.gov identifier: 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.

Key words::

• Canagliflozin
• Sodium glucose co-transporter 2 inhibitor
• Urinary glucose excretion
• Urinary tract infection

Transparency

Declaration of funding

The study DIA 2001 was funded by Johnson & Johnson Pharmaceutical Research & Development, LLC.

Declaration of financial/other interests

G.C., K.U., and K.W. are employees of Johnson & Johnson Pharmaceutical Research & Development, LLC. L.E.N. serves as a consultant to Johnson & Johnson Pharmaceutical Research and Development, LLC.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

Editorial assistance was provided by Phase Five Communications, Inc., funded by Janssen Global Services, LLC.

Previous presentation: a portion of this work has been previously presented as a poster entitled ‘No increase in bacteriuria or urinary tract infections in patients with type 2 diabetes mellitus, treated with canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor’ at the American Diabetes Association 71st Scientific Sessions, San Diego, CA, USA, 24–27 June 2011.