Antithrombotic effects of rosiglitazone-metformin versus glimepiride-metformin combination therapy in patients with type 2 diabetes mellitus and metabolic syndrome.
OBJECTIVE
To evaluate the differential effect on coagulation and fibrinolysis parameters of combination therapy with glimepiride-metformin and with rosiglitazone-metformin beyond their effect on glucose metabolism in patients with type 2 diabetes and metabolic syndrome.


METHODS
Multicenter, double-blind, randomized, controlled trial.


METHODS
Two university-affiliated medical centers in Italy.


METHODS
Ninety-five patients with type 2 diabetes for at least 6 months without glycemic control by diet and oral hypoglycemic agents to their maximum tolerated dosage and who also had metabolic syndrome.


METHODS
All 95 patients received metformin 1500 mg/day. In a randomized manner, 47 patients received glimepiride 2 mg/day and 48 patients received rosiglitazone 4 mg/day.


RESULTS
Body mass index (BMI), glycemic control, and coagulation and fibrinolysis parameters were evaluated at 3, 6, 9, and 12 months of treatment. Compared with baseline values, significant decreases in BMI, fasting plasma glucose, postprandial plasma glucose, and hemoglobin A1c were observed at 12 months in both the glimepiride and rosiglitazone groups (p<0.05 and p<0.01, respectively). Decreases in fasting plasma insulin and postprandial plasma insulin were observed at 12 months (p<0.05 and p<0.01, respectively) compared with baseline values in the rosiglitazone group. Furthermore, improvement in the Homeostasis Model Assessment index was observed only at 9 and 12 months (p<0.05 and p<0.01, respectively) compared with baseline in the rosiglitazone group. Significant improvement in plasminogen activator inhibitor (PAI)-1 was present in the rosiglitazone group after 9 months (p<0.05), and significant PAI-1 improvement was observed in the glimepiride and rosiglitazone groups after 12 months (p<0.05 and p<0.01, respectively).


CONCLUSIONS
The rosiglitazone-metformin combination significantly improved the long-term control of all insulin resistance-related parameters compared with the glimepiride-metformin combination. However, both combinations were associated with a slight but statistically significant improvement in PAI-1 value, related to a similar reduction in insulin resistance.
Derosa
Giuseppe
G
Department of Internal Medicine and Therapeutics, University of Pavia, Italy. giuderosa@tin.it
Gaddi
Antonio V
AV
Piccinni
Mario N
MN
Ciccarelli
Leonardina
L
Salvadeo
Sibilla
S
Peros
Emmanouil
E
Ghelfi
Morena
M
Ferrari
Ilaria
I
Cicero
Arrigo F G
AF
D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy*; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D010959:Tissue Plasminogen Activator / Q000097:blood
D001786:Blood Glucose; D005340:Fibrinogen; D005343:Fibrinolytic Agents; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D017395:Plasminogen Activator Inhibitor 1; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D010959:Tissue Plasminogen Activator; C057619:glimepiride