Changes in prandial glucagon levels after a 2-year treatment with vildagliptin or glimepiride in patients with type 2 diabetes inadequately controlled with metformin monotherapy

Abstract

Objective: To determine if the dipeptidyl peptidase-4 inhibitor vildagliptin more effectively inhibits glucagon levels than the sulfonylurea glimepiride during a meal.

Research design and methods: Glucagon responses to a standard meal were measured at baseline and study end point (mean 1.8 years) in a trial evaluating add-on therapy to metformin with 50 mg vildagliptin b.i.d. compared with glimepiride up to 6 mg q.d. in type 2 diabetes (baseline A1C 7.3 +/- 0.6%).

Results: A1C and prandial glucose area under the curve (AUC)(0-2 h) were reduced similarly in both groups, whereas prandial insulin AUC(0-2 h) increased to a greater extent by glimepiride. Prandial glucagon AUC(0-2 h) (baseline 66.6 +/- 2.3 pmol . h(-1) . l(-1)) decreased by 3.4 +/- 1.6 pmol . h(-1) . l(-1) by vildagliptin (n = 137) and increased by 3.8 +/- 1.7 pmol . h(-1) . l(-1) by glimepiride (n = 121). The between-group difference was 7.3 +/- 2.1 pmol . h(-1) . l(-1) (P < 0.001).

Conclusions: Vildagliptin therapy but not glimepiride improves postprandial alpha-cell function, which persists for at least 2 years.

Figure 1

Changes in prandial glucagon AUC_{0–2 h}, prandial GLP-1 AUC_{2 h}, insulin secretory rate relative to glucose (ISR/G), and HOMA-IR after up to a 2-year (mean 1.8 years) add-on treatment with vildagliptin (50 mg b.i.d.; n = 137) or glimepiride (up to 6 mg; n = 121) in patients with type 2 diabetes inadequately controlled with prior metformin therapy. Means ± SD are shown. The asterisk indicates P < 0.001 (A), P < 0.001 (B), P = 0.022 (C), and P < 0.001 (D) between the groups.