Empagliflozin Treatment Is Associated With Improved β-Cell Function in Type 2 Diabetes Mellitus

Objective: To examine whether lowering plasma glucose concentration with the sodium-glucose transporter-2 inhibitor empagliflozin improves beta-cell function in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM (N = 15) received empagliflozin (25 mg/d) for 2 weeks. beta-Cell function was measured with a nine-step hyperglycemic clamp (each step, 40 mg/dL) before and at 48 hours and at 14 days after initiating empagliflozin. Results: Glucosuria was recorded on days 1 and 14 [mean +/- standard error of the mean (SEM), 101 +/- 10 g and 117 +/- 11 g, respectively] after initiating empagliflozin, as were reductions in fasting plasma glucose levels (25 +/- 6 mg/dL and 38 +/- 8 mg/dL, respectively; both P < 0.05). After initiating empagliflozin and during the stepped hyperglycemic clamp, the incremental area under the plasma C-peptide concentration curve increased by48% +/- 12% at 48 hours and61% +/- 10% at 14 days (both P < 0.01); glucose infusion rate increased by 15% on day 3 and 16% on day 14, compared with baseline (both P < 0.05); and beta-cell function, measured with the insulin secretion/insulin resistance index, increased by 73% +/- 21% at 48 hours and 112% +/- 20% at 14 days (both P < 0.01). beta-cell glucose sensitivity during the hyperglycemic clamp was enhanced by 42% at 14 hours and 54% at 14 days after initiating empagliflozin (both P < 0.01). Conclusion: Lowering the plasma glucose concentration with empagliflozin in patients with T2DM augmented b-cell glucose sensitivity and improved beta-cell function.