The Effects of High- and Medium-Dose Metformin Therapy on Cardiovascular Risk Factors in Patients With Type II Diabetes

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OBJECTIVETo study the dose response to metformin in type II diabetic patients.RESEARCH DESIGN AND METHODSType II diabetic patients with a BMI greater than 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.RESULTSThere 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 less than 0.001 and NS compared with placebo). HbA1c and plasma insulin fell in both treatment groups (HbA (1c), P less than 0.001; insulin, P less than 0.003 and 0.03). There was a fall in triglyceride (P less than 0.05) and cholesterol (P less than 0.008) with high-dose metformin. PAI-1 antigen and activity fell by approximately 20 percent of baseline in both treatment groups (PAI-1 antigen high dose, P less than; PAI-1 antigen low dose, P less than 0.002; PAI-1 activity high and low dose, P less than 0.003). There were significant falls in total tPA in both groups (P less than 0.004), but the overall effect was a fall in ECLT (P less than 0.03).CONCLUSIONSThe 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.

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