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


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.
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Koichiro
K
Azuma
Zofia
Z
Rádiková
Juliet
J
Mancino
Frederico G S
FG
Toledo
Ernestine
E
Thomas
Cyrous
C
Kangani
Chiara
C
Dalla Man
Claudio
C
Cobelli
Jens J
JJ
Holst
Carolyn F
CF
Deacon
Yanling
Y
He
Monica
M
Ligueros-Saylan
Denise
D
Serra
James E
JE
Foley
David E
DE
Kelley
D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D019518:Postprandial Period; D011759:Pyrrolidines / Q000627:therapeutic use*; D000077597:Vildagliptin
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D002097:C-Reactive Protein; D000077597:Vildagliptin; D005947:Glucose; D000218:Adamantane