title: Urinary tract infections in patients with diabetes treated with dapagliflozin.
abstract: OBJECTIVE
  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 10mg) or placebo once daily, either as monotherapy or add-on to metformin, insulin, sulfonylurea, or thiazolidinedione for 12-24weeks. 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 (2.5mg [n=814], 5mg [n=1145], or 10mg [n=1193]) as monotherapy or add-on treatment, and 1393 placebo-treated patients. For dapagliflozin 2.5mg, 5mg, 10mg, 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 10mg 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.
authors.affiliation: AstraZeneca, Mölndal, Sweden. Electronic address: kristina.m.johnsson@astrazeneca.com.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Johnsson
authors.forename: Agata
authors.initials: A
authors.lastname: Ptaszynska
authors.forename: Bridget
authors.initials: B
authors.lastname: Schmitz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sugg
authors.forename: Shamik J
authors.initials: SJ
authors.lastname: Parikh
authors.forename: James F
authors.initials: JF
authors.lastname: List
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006029:Glycosuria / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors*; D014552:Urinary Tract Infections / Q000453:epidemiology*
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D051247:Sodium-Glucose Transport Proteins; C529054:dapagliflozin; D008687:Metformin
keywords: Dapagliflozin; Glucosuria; SGLT2; Sodium glucose cotransporter 2; UTI; Urinary tract infection