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SGLT2 Inhibitors and Risk of UTI Development in Patients with Diabetes

Does the newest class of diabetes medications increase UTI development?… 

A new study assessed safety data from 12 separate randomized, placebo-controlled trials involving dapagliflozin including clinical diagnosis of UTI and events that suggest UTI such as dysuria or cystitis. The safety data was collected, analyzed and reported as a proportion/percentage. However this study did not run any statistical tests to report correlation or statistical difference between groups.

The analysis included 4545 patients from 12 trials with 3152 patients in treatment groups (dapagliflozin dose/day: 2.5 mg [n = 814], 5 mg [n = 1145], or 10 mg [n = 1193]) and 1393 patients in the placebo group. The 5mg and 10mg dapagliflozin treatment groups experienced more symptoms of UTI compared to the placebo and 2.5mg dapagliflozin treatment group (placebo: 4.2%; 2.5mg group: 4.5%; 5mg group: 7.3%; 10mg group: 6.5%). Of those patients who had symptoms suggestive of UTI, approximately 50% of them had urine cultures obtained for clinical diagnosis of UTI but the trend was more clinically diagnosed UTIs were present in the 5mg and 10mg dapagliflozin group as compared to the placebo and 2.5mg treatment groups (placebo: 3.6%; 2.5mg group: 3.7%; 5mg group: 5.7%; 10mg group: 4.3%).

In conclusion, treatment with 5mg or 10mg of dapagliflozin may be associated with a slight increased risk of development of UTI or UTI symptoms. However the study lacked analysis of correlation of glycosuria and UTI development. Currently there are phase IV studies being completed on canagliflozin.

Practice Pearls
  • Dapagliflozin has a NDA with the FDA as of July 2013 and has the same mechanism of action as Canagliflozin, Invokana®, the newly approved diabetes medication in the US, which increases the amount of glucose excreted in the urine.
  • Persons with type 2 diabetes have an increased incidence of UTIs which may be related to hyperglycemia, glycosuria and/or neurogenic bladder associated with diabetes.
  • Hyperglycemia has been associated with impairment of the host defense system against bacteria and glycosuria has been proposed to provide "food" to bacteria to thrive on. However some data suggests a significantly high glucose concentration in the urine (without maintaining pH) can actually decrease bacterial growth.

Johnsson, Kristina, et al. Urinary Tract Infections in Patients with Diabetes Treated with Dapagliflozin. Journal of Diabetes and Its Complications 27 (2013) 473–478