Effect of combination glipizide GITS/metformin on fibrinolytic and metabolic parameters in poorly controlled type 2 diabetic subjects.
OBJECTIVE
Epidemiological studies have implicated increased plasminogen-activated inhibitor 1 (PAI-1) as a marker or predictor of accelerated coronary atherosclerotic disease in type 2 diabetes. We sought to determine whether metabolic control, independent of its oral mode of implementation, affects PAI-1 in patients with marked hyperglycemia.


METHODS
A total of 91 subjects were screened, subjected to a 4-week drug washout, and randomized to daily treatment with glipizide GITS (maximum 20 mg, n = 46) or metformin (maximum 2,550 mg, n = 45) as monotherapy. After monotherapy, combination therapy was initiated by adding the second agent to the regimen. Plasma glucose (fasting and postprandial), HbA(1c), fructosamine, and PAI-1 were assayed before and after randomization and sequentially thereafter in all subjects; hepatic glucose output (HGO) and abdominal fat distribution were each measured in a subset of subjects.


RESULTS
Glycemic control was markedly impaired at baseline (mean HbA(1c) 10.4 +/- 0.2% glipizide GITS; 10.0 +/- 0.2% metformin) but improved comparably with each agent as monotherapy and in combination (P < 0.0001 vs. baseline), as assessed with meal tolerance studies, fructosamine values, and HGO. Body weight and abdominal fat distribution did not change significantly in either group. PAI-1 concentrations were extraordinarily high (5- to 10-fold more than normal) at baseline (202 +/- 12 ng/ml glipizide GITS; 201 +/- 13 ng/ml metformin) but declined comparably, and significantly, after treatment with either agent as monotherapy and decreased further with combination therapy.


CONCLUSIONS
When hyperglycemia is profound, increases in PAI-1 are also profound. Control of hyperglycemia with either glipizide GITS, an insulin secretagogue, or metformin as monotherapy comparably ameliorates elevated PAI-1.
Cefalu
William T
WT
Department of Medicine, University of Vermont College of Medicine, Burlington 05401, USA. william.cefalu@uvm.edu
Schneider
David J
DJ
Carlson
Harold E
HE
Migdal
Phyllis
P
Gan Lim
Leonil
L
Izon
Meriam P
MP
Kapoor
Anoop
A
Bell-Farrow
Audrey
A
Terry
James G
JG
Sobel
Burton E
BE
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005342:Fibrinolysis / Q000187:drug effects*; D005913:Glipizide / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012107:Research Design
D001786:Blood Glucose; D005913:Glipizide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin