Urinary tract infections in patients with diabetes treated with dapagliflozin

• Published in: Journal of diabetes and its complications 2013-09, Vol.27 (5), p.473-478
• Main Authors: Johnsson, Kristina M, Ptaszynska, Agata, Schmitz, Bridget, Sugg, Jennifer, Parikh, Shamik J, List, James F
• Format: Article
• Language: English
• Subjects: Aged; Benzhydryl Compounds; Clinical trials; Dapagliflozin; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Endocrinology & Metabolism; Female; Glucosides - therapeutic use; Glucosuria; Glycosuria - chemically induced; Glycosuria - epidemiology; Humans; Hyperglycemia; Hypoglycemic Agents - therapeutic use; Incidence; Infections; Male; Metformin - therapeutic use; Middle Aged; Randomized Controlled Trials as Topic; SGLT2; Sodium glucose cotransporter 2; Sodium-Glucose Transport Proteins - antagonists & inhibitors; Studies; Urinary tract infection; Urinary Tract Infections - epidemiology; Urogenital system; UTI
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2013.05.004

Abstract Aims Urinary tract infection is common in patients with type 2 diabetes. Possible causative factors include glucosuria, which is a result of treatment with sodium glucose cotransporter 2 (SGLT2) inhibitors. Dapagliflozin is an investigative SGLT2 inhibitor with demonstrated glycemic benefits in patients with diabetes. Data from dapagliflozin multi-trial safety data were analyzed to clarify the association between glucosuria and urinary tract infection. Methods Safety data from 12 randomized, placebo-controlled trials were pooled to evaluate the relationship between glucosuria and urinary tract infection in patients with inadequately controlled diabetes (HbA1c > 6.5%–12%). Patients were treated with dapagliflozin (2.5, 5, or 10 mg) or placebo once daily, either as monotherapy or add-on to metformin, insulin, sulfonylurea, or thiazolidinedione for 12–24 weeks. The incidence of clinical diagnoses and events suggestive of urinary tract infection were quantified. Results This analysis included 3152 patients who received once-daily dapagliflozin (2.5 mg [ n = 814], 5 mg [ n = 1145], or 10 mg [ n = 1193]) as monotherapy or add-on treatment, and 1393 placebo-treated patients. For dapagliflozin 2.5 mg, 5 mg, 10 mg, and placebo, diagnosed infections were reported in 3.6%, 5.7%, 4.3%, and 3.7%, respectively. Urinary glucose levels, but not the incidence of urinary tract infection, increased progressively with dapagliflozin dosage. Most identified infections were those considered typical for patients with diabetes. Discontinuations due to urinary tract infection were rare: 8 (0.3%) dapagliflozin-treated patients and 1 (0.1%) placebo-treated patient. Most diagnosed infections were mild to moderate and responded to standard antimicrobial treatment. Conclusions Treatment of type 2 diabetes with once-daily dapagliflozin 5 or 10 mg is accompanied by a slightly increased risk of urinary tract infection. Infections were generally mild to moderate and clinically manageable. This analysis did not demonstrate a definitive dose relationship between glucosuria and urinary tract infection.