Cholesterol lowering effect of metformin in combined hyperlipidemia: placebo controlled double blind trial

Metformin, an antidiabetic biguanide derivative, prevents experimental atherosclerosis and induces structural changes in lipoproteins in experimental animals. In the present study we investigated the effect of metformin on serum lipoproteins and platelet function in 24 non-diabetic patients with type II B hyperlipidemia. The patients were randomly given metformin in two dosage levels (1.0 g/day and 2.0 g/day) and placebo for periods of nine weeks in a crossover trial. Metformin caused a dose dependent fall in the concentrations of total serum cholesterol and of LDL-cholesterol. The average concentration of total cholesterol was 8.54 +/- 0.22 (SE) mmol/l, 8.12 +/- 0.19 mmol/l and 7.79 +/- 0.15 mmol/l during placebo, metformin 1.0 g/day and 2.0 g/day treatments, respectively. Both metformin values differed significantly (P less than 0.05) from the placebo value. Thus there was an average fall of 8.1% in total cholesterol after the higher metformin dose. LDL-cholesterol was 5.25 +/- 0.23 mmol/l after placebo, falling by 3.1% and 9.6% after metformin doses of 1.0 g/day and 2.0 g/day, respectively. The concentrations of HDL-cholesterol and total serum triglycerides showed no significant changes. Body weight, blood glucose, plasma insulin, blood lactate, platelet function and urinary excretion of prostanoids remained unchanged during the study. The reduction of total- and LDL-cholesterol levels may be a welcome additional consequence of metformin during treatment of diabetic patients with hypercholesterolemia.