Robust improvements in fasting and prandial measures of beta-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy database.
OBJECTIVE
To assess the effects of 24-week treatment with vildagliptin on measures of beta-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM).


METHODS
Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of beta-cell function [homeostasis model assessment of beta-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test-derived) measures of beta-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29).


RESULTS
In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AMDelta) = 10.3 +/- 1.5] and vs. placebo (between-treatment difference in AMDelta = 11.5 +/- 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AMDelta = -0.05 +/- 0.01) and vs. placebo (between-treatment difference in AMDelta = -0.09 +/- 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test-derived parameters, and ISR/G (between-treatment difference in AMDelta = 9.8 +/- 2.8 pmol/min/m(2)/mM, p < 0.001) and the insulinogenic index(0-peak glucose) (between-treatment difference in AMDelta = 0.24 +/- 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo.


CONCLUSIONS
Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test-derived measures of beta-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov.
Pratley
R E
RE
University of Vermont College of Medicine, Burlington, VT, USA.
Schweizer
A
A
Rosenstock
J
J
Foley
J E
JE
Banerji
M A
MA
Pi-Sunyer
F X
FX
Mills
D
D
Dejager
S
S
D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009570:Nitriles / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D000077597:Vildagliptin
D000218:Adamantane; D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin