TY - JOUR

T1 - Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes

AU - Azuma, Koichiro

AU - Rádiková, Zofia

AU - Mancino, Juliet

AU - Toledo, Frederico G S

AU - Thomas, Ernestine

AU - Kangani, Cyrous

AU - Dalla Man, Chiara

AU - Cobelli, Claudio

AU - Holst, Jens J

AU - Deacon, Carolyn F

AU - He, Yanling

AU - Ligueros-Saylan, Monica

AU - Serra, Denise

AU - Foley, James E

AU - Kelley, David E

N1 - Keywords: Adamantane; Blood Glucose; C-Reactive Protein; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Nitriles; Postprandial Period; Pyrrolidines

PY - 2007

Y1 - 2007

N2 - OBJECTIVE: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. Research DESIGN AND METHODS: Participants with T2DM (n = 16) who had a baseline hemoglobin A(1c) of 7.1 +/- 0.2% completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min x m(2) insulin infusions. RESULTS: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 +/- 0.3 mmol/liter and 1.6 +/- 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P <0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01). CONCLUSIONS: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.

AB - OBJECTIVE: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. Research DESIGN AND METHODS: Participants with T2DM (n = 16) who had a baseline hemoglobin A(1c) of 7.1 +/- 0.2% completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min x m(2) insulin infusions. RESULTS: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 +/- 0.3 mmol/liter and 1.6 +/- 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P <0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01). CONCLUSIONS: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.

U2 - 10.1210/jc.2007-1369

DO - 10.1210/jc.2007-1369

M3 - Journal article

C2 - 18042650

VL - 93

SP - 459

EP - 464

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -