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.

Rimei Nishimura,Søren S Lund,Uli C Broedl,Thomas Hach,Kohei Inoue,Afshin Salsali,Kazuki Koiwai,Yuko Tanaka

doi:10.1186/s12933-014-0169-9

Abstract

BackgroundThis study evaluated the effect of empagliflozin on postprandial glucose (PPG) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM).MethodsPatients (N = 60; baseline mean [SD] HbA1c 7.91 [0.80]%; body mass index 24.3 [3.2] kg/m2) 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.ResultsAdjusted 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.ConclusionEmpagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM.Trial registrationClinicaltrials.gov NCT01947855Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-014-0169-9) contains supplementary material, which is available to authorized users.

Highlights

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)
Statistical analysis Efficacy analyses were performed on the full analysis set (FAS) which included patients treated with ≥1 dose of study drug who had a baseline value for AUC1-4h for PPG
Efficacy Compared with placebo, empagliflozin 10 mg and 25 mg led to significant reductions from baseline in AUC1-4h for PPG at day 1 and at day 28 (Figure 2A) and in AUC10-13h for PPG at day 1 and at day 28 (Figure 2B)

Summary

Results

Patients Of 78 patients screened, 60 patients were randomized and treated and comprised the FAS. Changes from baseline in 2-hour PPG were significantly greater with empagliflozin 10 mg and 25 mg compared with placebo after breakfast at day 1 and day 28 (Figure 2C). Changes from baseline in 2-hour PPG after dinner were significantly different with empagliflozin 10 mg and empagliflozin 25 mg compared with placebo at day 28 but not at day 1 (Figure 2C). Empagliflozin 10 mg and 25 mg led to significant reductions from baseline in 24-hour mean glucose compared with placebo at day 1 and at day 28 (Figure 4). Reductions from baseline in 24-hour mean glucose compared with placebo at day 28 were greater with empagliflozin 25 mg than empagliflozin 10 mg. Reductions from baseline in the excretion of 8-iso-PGF2α in the hours after study drug administration were only significantly different with empagliflozin mg compared with placebo at day 28 (Table 3). Changes from baseline in hematocrit and eGFR were generally small in all groups (Additional file 1: Table S4)

Background

Methods

Conclusions