The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes.
OBJECTIVE
To study the dose response to metformin in type II diabetic patients.


METHODS
Type II diabetic patients with a BMI > 25 were treated with 3,000 mg/day (n = 27), 1,500 mg/day (n = 25), or placebo (n = 23) for 6 months. Venous blood samples were taken at each visit for plasma glucose and insulin, HbA1c, triglyceride and cholesterol, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (tPA), and euglobulin clot lysis time (ECLT). Blood pressure was recorded at each visit.


RESULTS
There were no changes in BMI or blood pressure. Blood glucose fell (mean) by 3.6 mmol/l in the high-dose and 0.5 mmol/l in the low-dose group over the 6-month study (P < 0.001 and NS compared with placebo). HbA1c and plasma insulin fell in both treatment groups (HbA1c, P < 0.001; insulin, P < 0.003 and 0.03). There was a fall in triglyceride (P < 0.05) and cholesterol (P < 0.008) with high-dose metformin. PAI-1 antigen and activity fell by approximately 20% of baseline in both treatment groups (PAI-1 antigen high dose, P < 0.01; PAI-1 antigen low dose, P < 0.002: PAI-1 activity high and low dose, P < 0.003). There were significant falls in total tPA in both groups (P < 0.004), but the overall effect was a fall in ECLT (P < 0.03).


CONCLUSIONS
The results indicate that metformin has favorable effects on cardiovascular risk factors associated with type II diabetes. The effects on glycemic control and lipids are dose-dependent, while the enhanced fibrinolytic response is independent of the doses used.
Grant
P J
PJ
Diabetes and Thrombosis Research Group, University of Leeds, UK.
D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D014280:Triglycerides