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

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.

Figure 1

MTT and plasma glucose sampling schedule at baseline, day 1 and day 28. *Shortly before MTT; ^†CGM was started shortly before trial drug administration and continued until 24 hours after trial drug administration. MTT: meal tolerance test. CGM, continuous glucose monitoring.

Figure 2

Changes from baseline in (A) AUC _1-4 h for PPG, (B) AUC _10-13 h for PPG and (C) 2-hour PPG after each meal, based on analyses of covariance in the full analysis set. CI, confidence interval; PPG, postprandial glucose; SE, standard error.

Figure 3

Change from baseline in FPG at day 2 and day 29 based on analyses of covariance in the full analysis set. CI, confidence interval; FPG, fasting plasma glucose; SE, standard error.

Figure 4

Change from baseline in 24-hour mean glucose by CGM based on analyses of covariance in the full analysis set. CGM, continuous glucose monitoring; CI, confidence interval; SE, standard error.

Figure 5

Mean glucose over 24 hours by CGM. CGM, continuous glucose monitoring.

Figure 6

Percentage of time with glucose level ≥180 mg/dl, ≥70 to <180 mg/dl, and <70 mg/dl, based on analyses of covariance in the full analysis set. Baseline data are means, day 1 and day 28 data are adjusted means. **p<0.01; ***p<0.001 for difference vs placebo in change from baseline; ^†n=20 at day 28.