Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes.
OBJECTIVE
The dipeptidyl peptidase IV inhibitor, vildagliptin, increases levels of intact glucagon-like peptide-1 (GLP-1) and improves glycemic control in patients with type 2 diabetes. Although GLP-1 is known to stimulate insulin secretion, vildagliptin does not affect plasma insulin levels in diabetic patients, suggesting that more sophisticated measures are necessary to ascertain the influence of vildagliptin on beta-cell function.


METHODS
This study examined the effects of 28-d treatment with vildagliptin (100 mg, twice daily; n = 9) vs. placebo (n = 11) on beta-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (beta-cell dose response), the change in glucose with time (derivative component), and a potentiation factor, which is a function of time and may reflect the actions of nonglucose secretagogues and other factors.


RESULTS
Vildagliptin significantly increased the insulin secretory rate at 7 mmol/liter glucose (secretory tone), calculated from the dose response; the difference in least squares mean (deltaLSM) was 101 +/- 51 pmol.min(-1).m(-2) (P = 0.002). The slope of the beta-cell dose response, the derivative component, and the potentiation factor were not affected. Vildagliptin also significantly decreased mean prandial glucose (deltaLSM, -1.2 +/- 0.4 mmol/liter; P = 0.01) and glucagon (deltaLSM, -10.7 +/- 4.8 ng/liter; P = 0.03) levels and increased plasma levels of intact GLP-1 (deltaLSM, +10.8 +/- 1.6 pmol/liter; P < 0.0001) and gastric inhibitory polypeptide (deltaLSM, +43.4 +/- 9.4 pmol/liter; P < 0.0001) relative to placebo.


CONCLUSIONS
Vildagliptin is an incretin degradation inhibitor that improves beta-cell function in diabetic patients by increasing the insulin secretory tone.
Mari
A
A
National Research Center, Institute of Biomedical Engineering, Corso Stati Uniti 4, 35127 Padova, Italy. andrea.mari@isib.cnr.it
Sallas
W M
WM
He
Y L
YL
Watson
C
C
Ligueros-Saylan
M
M
Dunning
B E
BE
Deacon
C F
CF
Holst
J J
JJ
Foley
J E
JE
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058892:Adenosine Deaminase Inhibitors; D000328:Adult; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009570:Nitriles; D011759:Pyrrolidines; D016896:Treatment Outcome; D000077597:Vildagliptin
D058892:Adenosine Deaminase Inhibitors; D001786:Blood Glucose; D002096:C-Peptide; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane