title: Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events.
abstract: BACKGROUND
  Dapagliflozin reduces hyperglycaemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion.
  
  
  OBJECTIVE
  This study determined the overall safety profile of dapagliflozin in T2DM.
  
  
  METHODS
  Safety of dapagliflozin in pooled analyses of phase IIb/III studies was evaluated. Patients received comparator or dapagliflozin as monotherapy, add-on to antidiabetic therapy, or as initial combination with metformin. Proportions of patients with adverse events (AEs) and prespecified parameters related to previous clinical observations and dapagliflozin's action were assessed. The principal analysis used data from 12 placebo-controlled studies. Rare events were assessed across phase IIb/III studies, including special populations, comparator-controlled trials and ongoing long-term extensions.
  
  
  RESULTS
  In placebo-controlled studies, hypoglycaemia was more common with dapagliflozin (11.8 %) than placebo (7.0 %), with imbalance driven by add-on of dapagliflozin to sulfonylurea or insulin. Urinary tract infections (4.8 vs 3.7 %), vulvovaginitis/balanitis and related infections (5.1 vs 0.9 %), and non-serious volume-related events (0.8 vs 0.4 %) occurred more often with dapagliflozin than placebo. No substantial AEs were seen on electrolytes or renal function. Pyelonephritis was rare and balanced among treatments; there were no imbalances in fractures or liver test elevations. Overall incidence of malignancies was balanced between groups. The incidence rate ratios of malignancy in certain organ systems were slightly lower for dapagliflozin (renal tract, female reproductive) and in others were slightly lower for control (breast, prostate, bladder). Most AEs associated with dapagliflozin were mild/moderate and related to the mechanism of action.
  
  
  CONCLUSIONS
  Dapagliflozin has a favourable and predictable tolerability profile, with reported events related to its mechanism of action.
authors.affiliation: Bristol-Myers Squibb, Global Clinical Research, Research and Development, Princeton, NJ, 08543-4000, USA, agata.ptaszynska@bms.com.
authors.forename: Agata
authors.initials: A
authors.lastname: Ptaszynska
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Johnsson
authors.forename: Shamik J
authors.initials: SJ
authors.lastname: Parikh
authors.forename: Tjerk W A
authors.initials: TW
authors.lastname: de Bruin
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Apanovitch
authors.forename: James F
authors.initials: JF
authors.lastname: List
mesh_terms: D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; C529054:dapagliflozin; D008687:Metformin
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