title: Glucose Exposure and Variability with Empagliflozin as Adjunct to Insulin in Patients with Type 1 Diabetes: Continuous Glucose Monitoring Data from a 4-Week, Randomized, Placebo-Controlled Trial (EASE-1).
abstract: We evaluated the effect of empagliflozin as adjunct to insulin on 24-h glucose exposure and variability in patients with type 1 diabetes.
  
  
  
  Patients (N = 75) with HbA1c≥7.5% to ≤10.5% were randomized to receive empagliflozin 2.5 mg, empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily as adjunct to insulin for 4 weeks. Insulin dose was to be kept as stable as possible during week 1 of treatment and was freely adjustable thereafter. Markers of glucose exposure and variability were assessed from 7-day blinded continuous glucose monitoring intervals. This study is completed ( ClinicalTrials.gov NCT01969747).
  
  
  
  Empagliflozin reduced hourly mean glucose area under the median curve over 24 h versus placebo within week 1 (adjusted mean differences: -12.2 mg/dL·h [95% confidence interval -23.9 to -0.5], -30.2 mg/dL·h [-42.2 to -18.2], and -33.0 mg/dL·h [-44.8 to -21.1] with empagliflozin 2.5, 10, and 25 mg, respectively; all P < 0.05) and increased time in glucose target range (>70 to ≤180 mg/dL). Results were sustained to week 4 with empagliflozin 25 mg. All empagliflozin doses significantly reduced glucose variability (interquartile range and mean amplitude of glucose excursions) versus placebo at weeks 1 and 4. Except for small increases in hours per day with glucose ≤70 mg/dL during the stable insulin period, empagliflozin did not increase time in hypoglycemia compared with placebo.
  
  
  
  In patients with type 1 diabetes, empagliflozin as adjunct to insulin decreased glucose exposure and variability and increased time in glucose target range.
authors.affiliation: 1 Profil GmbH , Neuss, Germany .
authors.forename: Susanne
authors.initials: S
authors.lastname: Famulla
authors.affiliation: 2 Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz , Graz, Austria .
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.affiliation: 3 Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach, Germany .
authors.forename: Jens
authors.initials: J
authors.lastname: Eilbracht
authors.affiliation: 3 Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach, Germany .
authors.forename: Dietmar
authors.initials: D
authors.lastname: Neubacher
authors.affiliation: 4 Boehringer Ingelheim Canada Ltd./Ltee , Burlington, Canada .
authors.forename: Nima
authors.initials: N
authors.lastname: Soleymanlou
authors.affiliation: 5 Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim, Germany .
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: 5 Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim, Germany .
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
authors.affiliation: 5 Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim, Germany .
authors.forename: Stefan
authors.initials: S
authors.lastname: Kaspers
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; C570240:empagliflozin
keywords: Continuous glucose monitoring; HbA1c; Hyperglycemia; Hypoglycemia; Postprandial blood glucose; Type 1 diabetes