Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study

Cardiovasc Diabetol. 2015 Jan 30;14:11. doi: 10.1186/s12933-014-0169-9.

Abstract

Background: This study evaluated the effect of empagliflozin on postprandial glucose (PPG) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods: Patients (N = 60; baseline mean [SD] HbA1c 7.91 [0.80]%; body mass index 24.3 [3.2] kg/m(2)) were randomized to receive empagliflozin 10 mg (n = 20), empagliflozin 25 mg (n = 19) or placebo (n = 21) once daily as monotherapy for 28 days. A meal tolerance test and continuous glucose monitoring (CGM) for 24 hours were performed at baseline and on days 1 and 28. The primary endpoint was change from baseline in area under the glucose concentration-time curve 3 hours after breakfast (AUC1-4h for PPG) at day 28.

Results: Adjusted mean (95%) differences versus placebo in changes from baseline in AUC1-4h for PPG at day 1 were -97.1 (-126.5, -67.8) mg · h/dl with empagliflozin 10 mg and -91.6 (-120.4, -62.8) mg · h/dl with empagliflozin 25 mg (both p < 0.001 versus placebo) and at day 28 were -85.5 (-126.0, -45.0) mg · h/dl with empagliflozin 10 mg and -104.9 (-144.8, -65.0) mg · h/dl with empagliflozin 25 mg (both p < 0.001 versus placebo). Adjusted mean (95% CI) differences versus placebo in change from baseline in 24-hour mean glucose (CGM) at day 1 were -20.8 (-27.0, -14.7) mg/dl with empagliflozin 10 mg and -23.9 (-30.0, -17.9) mg/dl with empagliflozin 25 mg (both p < 0.001 versus placebo) and at day 28 were -24.5 (-35.4, -13.6) mg/dl with empagliflozin 10 mg and -31.7 (-42.5,-20.9) mg/dl with empagliflozin 25 mg (both p < 0.001 versus placebo). Changes from baseline in mean amplitude of glucose excursions (MAGE; CGM) were not significantly different with either empagliflozin dose versus placebo at either timepoint. Curves of mean glucose (CGM) did not change between baseline and day 1 or 28 with placebo, but shifted downward with empagliflozin. Percentage of time with glucose ≥70 to <180 mg/dl increased from 52.0% at baseline to 77.0% at day 28 with empagliflozin 10 mg and from 55.0% to 81.1% with empagliflozin 25 mg, without increasing time spent with hypoglycemia.

Conclusion: Empagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM.

Trial registration: Clinicaltrials.gov NCT01947855.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian Continental Ancestry Group*
  • Benzhydryl Compounds / pharmacology
  • Benzhydryl Compounds / therapeutic use*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Double-Blind Method
  • Female
  • Glucosides / pharmacology
  • Glucosides / therapeutic use*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Postprandial Period / drug effects
  • Postprandial Period / physiology*
  • Time Factors
  • Treatment Outcome

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01947855