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

Abstract

Objective: To examine whether lowering plasma glucose concentration with the sodium-glucose transporter-2 inhibitor empagliflozin improves β-cell function in patients with type 2 diabetes mellitus (T2DM).

Methods: Patients with T2DM (N = 15) received empagliflozin (25 mg/d) for 2 weeks. β-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 by 48% ± 12% at 48 hours and 61% ± 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 β-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). β-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 β-cell glucose sensitivity and improved β-cell function.

Figure 1.

Plasma glucose concentrations during the three hyperglycemic clamp studies performed at baseline and on days 2 and 14 after the start of empagliflozin therapy. Conc., concentration.

Figure 2.

(A) Plasma C-peptide response during the stepped hyperglycemic clamp performed at baseline and on days 2 and 14 after the start of empagliflozin therapy. (B) Correlation between the decrease in the FPG concentration and the log of the ratio of the plasma C-peptide response after 14 days of empagliflozin to the plasma C-peptide response at baseline. AUC_bl, plasma C-peptide response at baseline; AUC_empa, area under the curve after 14 days of empagliflozin; Conc, concentration.

Figure 3.

(A) Incremental AUC for the plasma C-peptide response at baseline and on days 2 and day 14 after the start of empagliflozin treatment. (B) GIR at baseline and on days 2 and 14 after the start of empagliflozin. (C) The IS/IR index at baseline and on days 2 and 14 after the start of empagliflozin treatment. *P < 0.05. AUC, area under the curve; BL, baseline; D2, day 2; D14, day 14; GIR, glucose infusion rate.

Figure 4.

Slope of the line relating the increment in plasma C-peptide concentration and the increment in plasma glucose concentration during the stepped hyperglycemic clamp. Conc, concentration.