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)

Diabetes Technol Ther. 2017 Jan;19(1):49-60. doi: 10.1089/dia.2016.0261. Epub 2016 Dec 8.


Background: We evaluated the effect of empagliflozin as adjunct to insulin on 24-h glucose exposure and variability in patients with type 1 diabetes.

Methods: 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 ( NCT01969747).

Results: 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.

Conclusions: In patients with type 1 diabetes, empagliflozin as adjunct to insulin decreased glucose exposure and variability and increased time in glucose target range.

Keywords: Continuous glucose monitoring; HbA1c; Hyperglycemia; Hypoglycemia; Postprandial blood glucose; Type 1 diabetes.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzhydryl Compounds / therapeutic use*
  • Blood Glucose / analysis*
  • Blood Glucose Self-Monitoring
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucosides / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Male
  • Middle Aged
  • Treatment Outcome


  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Hypoglycemic Agents
  • Insulin
  • empagliflozin

Associated data