title: Dapagliflozin in the treatment of patients with type 2 diabetes presenting with high baseline A1C.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of dapagliflozin 5 and 10 mg/d versus placebo in patients with type 2 diabetes and high baseline A1C defined as A1C ≥ 9% or ≥ 10%.
  
  
  METHODS
  A post-hoc analysis was conducted of pooled data from 9, 24-week, placebo-controlled clinical studies investigating dapagliflozin as monotherapy, add-on therapy to other oral antidiabetes drugs or insulin, or initial combination therapy with metformin.
  
  
  RESULTS
  At week 24, dapagliflozin 5 and 10 mg/d decreased A1C (≥ 9%: -1.37% and -1.39%, respectively, vs. -0.65% with placebo, both P < 0.0001 and ≥ 10%: -2.13% [P < 0.0001] and -1.59% [P = 0.0003], respectively, vs. -0.82% with placebo), reduced fasting plasma glucose as early as week 1 (P < 0.001 for each dose at all time points for both treatments), and decreased body weight (≥ 9%: P < 0.0001 vs. placebo for both doses; ≥ 10%: P = 0.0065 vs. placebo, 10 mg/d only). Among patients with baseline A1C ≥ 9% who received dapagliflozin 5 or 10 mg/d, 15.7% and 18.9%, respectively, achieved a ≥ 5% decrease in body weight (both P < 0.0001 vs. 3.6% with placebo). Dapagliflozin 10 mg/d decreased systolic and diastolic blood pressure (P < 0.0001 and P = 0.0074 vs. placebo). Adverse events were generally similar across treatment groups, with the exception of a greater frequency of genital infections and hypoglycemia (mostly minor episodes not requiring third-party assistance) in patients receiving dapagliflozin.
  
  
  CONCLUSIONS
  In patients with poorly controlled type 2 diabetes defined as A1C ≥ 9% or ≥ 10%, dapagliflozin provided clinically meaningful improvements in glycemic parameters, body weight, and blood pressure, and was generally well tolerated, making it a good therapeutic option for patients with high A1C.
authors.affiliation: a Abington Jefferson Health, Family Medicine Residency Program , Jenkintown , PA , USA.|b Family and Community Medicine, Temple University School of Medicine , Philadelphia , PA , USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Skolnik
authors.affiliation: a Abington Jefferson Health, Family Medicine Residency Program , Jenkintown , PA , USA.
authors.forename: Harmony
authors.initials: H
authors.lastname: Bonnes
authors.affiliation: c AstraZeneca, US Medical Affairs , Fort Washington , PA , USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Yeh
authors.affiliation: c AstraZeneca, US Medical Affairs , Fort Washington , PA , USA.
authors.forename: Arie
authors.initials: A
authors.lastname: Katz
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human; C529054:dapagliflozin
keywords: A1C; dapagliflozin; post-hoc analysis; sodium-glucose cotransporter-2 inhibitor; type 2 diabetes