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

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 α-cell function, which persists for at least 2 years.