title: Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis.
abstract: BACKGROUND
  In patients with type 2 diabetes mellitus (T2DM), dapagliflozin improves glycemic control and has a safety profile typically related to its mechanism of action. Hypersensitivity adverse events (AEs) have been reported in some patients with sodium-glucose cotransporter 2 (SGLT2) inhibitors, including a recent report of dermatological AEs in Japan.
  
  
  METHODS
  We investigated the frequency and characteristics of hypersensitivity AEs, including potentially hypersensitivity-related skin AEs, across 21 phase IIb/III trials of dapagliflozin (N = 5936) versus active or placebo comparators (N = 3403), including the subpopulation of Asian patients (N = 1563).
  
  
  RESULTS
  Overall, AEs and serious AEs (SAEs) of hypersensitivity were infrequent and were reported in a similar proportion of patients with dapagliflozin versus active or placebo comparators (AEs: 4.5 vs. 4.3 %; SAEs: 0.2 vs. 0.1 %, respectively). The most common events affected the skin or subcutaneous tissue: rash (dapagliflozin: 1.1 %, comparator: 1.1 %), eczema (0.6, 0.8 %), dermatitis (0.5, 0.4 %), and urticaria (0.5, 0.2 %). Few patients discontinued as a result of hypersensitivity AEs (≤0.2 %). In patients of Asian descent, a lower frequency of hypersensitivity AEs was observed with dapagliflozin versus comparators (2.0 vs. 4.5 %). In the subset of placebo-controlled trials, hypersensitivity AEs were slightly more frequent with dapagliflozin than with placebo across the overall population (4.7 vs. 3.8 %), and less frequent with dapagliflozin in Asian patients (1.5 vs. 5.0 %).
  
  
  CONCLUSIONS
  The findings of this post hoc analysis indicate that dapagliflozin does not lead to an increased risk of serious hypersensitivity reactions or potentially hypersensitivity-related skin events among patients with T2DM, including Asian patients. Long-term outcome studies and postmarketing surveillance will provide further information on hypersensitivity reactions with SGLT2 inhibitors. CLINICALTRIALS.
  NCT01042977, NCT01031680, NCT00855166, NCT00984867, NCT01294423, NCT00673231, NCT00972244, NCT00680745, NCT00660907, NCT01095653, NCT00831779, NCT00976495, NCT00859898, NCT00736879, NCT00683878, NCT00663260, NCT00643851, NCT00528879, NCT00528372, NCT00357370, NCT00263276.
authors.affiliation: AstraZeneca Gothenburg, Patient Safety, Pepparredsleden 1, 43150, Mölndal, Sweden. annika.mellander@astrazeneca.com.
authors.forename: Annika
authors.initials: A
authors.lastname: Mellander
authors.affiliation: AstraZeneca Gothenburg, Patient Safety, Pepparredsleden 1, 43150, Mölndal, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Billger
authors.affiliation: AstraZeneca Gothenburg, Patient Safety, Pepparredsleden 1, 43150, Mölndal, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Johnsson
authors.affiliation: AstraZeneca Gothenburg, Patient Safety, Pepparredsleden 1, 43150, Mölndal, Sweden.
authors.forename: Anna Karin
authors.initials: AK
authors.lastname: Träff
authors.affiliation: AstraZeneca, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: AstraZeneca Gothenburg, Patient Safety, Pepparredsleden 1, 43150, Mölndal, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Johnsson
mesh_terms: D044466:Asian People; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin