Effect of pioglitazone versus metformin on cardiovascular risk markers in type 2 diabetes.
BACKGROUND
Besides its critical role in metabolic homeostasis, peroxisome proliferator-activated receptor (PPAR)-γ modulates several cellular responses involved in atherothrombosis. This multicenter, double-blind, randomized study investigated the effects of two oral hypoglycemic agents on markers of inflammation, platelet activation, thrombogenesis, and oxidative stress in patients with type 2 diabetes.


RESULTS
The primary objective of this study was to evaluate the effect on C-reactive protein (CRP) after a 16-week treatment period with either pioglitazone or metformin. Additionally, markers of vascular inflammatory response, platelet activation, thrombogenesis, oxidative stress, glucose, and lipid metabolism, as well as liver function, were measured. In total, 50 patients completed the study. Pioglitazone-treated patients were found to have statistically significantly larger decreases in mean CRP levels (-0.4 mg/dL) compared to those treated with metformin (-0.2 mg/dL) (P=0.04), as well as greater reductions in levels of mean fasting plasma glucose (-27 vs. -9 mg/dL; P=0.01), serum insulin (-2 vs. -1.9 mU/L; P=0.014), homeostatic model assessment (HOMA) (-1.2 vs. -0.9; P=0.015), and E-selectin (-12.4 vs. +3.4 μg/mL; P=0.01). Mean glycated hemoglobin (HbA1c) levels decreased in both treatment groups from baseline to week 16 (-0.4% in the pioglitazone group, -0.2% in the metformin group; P=0.36). Pioglitazone treatment was also found to be associated with a statistically significant increase in total cholesterol levels (+10 mg/dL in the pioglitazone arm, -3 mg/dL in the metformin arm; P=0.05) and a decrease in liver enzyme levels.


CONCLUSIONS
The favorable changes in markers of systemic and vascular inflammatory response with pioglitazone suggest that it may positively influence the atherothrombotic process in type 2 diabetes.
Cardiovascular and Metabolic Department, IRCCS MultiMedica Sesto San Giovanni, Milan, Italy.
Stefano
S
Genovese
Giorgia
G
De Berardis
Antonio
A
Nicolucci
Edoardo
E
Mannucci
Virgilio
V
Evangelista
Licia
L
Totani
Fabio
F
Pellegrini
Antonio
A
Ceriello
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D018384:Oxidative Stress; D000077205:Pioglitazone; D015539:Platelet Activation; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D002097:C-Reactive Protein; D008687:Metformin; D000077205:Pioglitazone