EFFECTS OF METFORMIN AND METOPROLOL CR ON HORMONES AND FIBRINOLYTIC VARIABLES DURING A HYPERINSULINEMIC, EUGLYCEMIC CLAMP IN MAN

The aim of this study was to characterize the acute effect of euglycem ic (glucose 5.2+/-0.6 mmol/l) hyperinsulinemia (mean 118+/- 32 mU/l) o n fibrinolytic variables, free fatty acids (FFA) and counterregulatory hormones. In addition, the effect of chronic treatment with metformin , an oral antidiabetic agent which enhances insulin action, and metopr olol CR, a relatively beta(1)-selective adrenergic antagonist, was als o evaluated. A randomized, double-blind, placebo-controlled, cross-ove r study including 18 non-obese men, aged 53+/-6 years, was performed. The investigations were performed after each treatment period of 6 wee ks in both the postabsorptive state and during a euglycemic, hyperinsu linemic clamp. Compared to the postabsorptive state, plasminogen activ ator inhibitor (PAI-1) activity and antigen, tissue plasminogen activa tor (t-PA) antigen and FFA decreased (p <0.001) after 120 min of eugly cemic hyperinsulinemia. In addition, t-PA activity increased (p <0.01) while blood levels of lipoprotein (a), catetholamines and cortisol re mained unchanged. Growth hormone increased during the clamps and this was most pronounced after treatment with metoprolol CR. When the effec t of treatment was compared, postabsorptive levels of C-peptide, FFA a nd t-PA antigen were lower after metformin than after the placebo peri od (p <0.05), t-PA antigen also remained lower during the clamp after merformin treatment. No significant effects of metformin or metoprolol CR were seen on insulin-stimulated glucose uptake during the clamps o r on postabsorptive levels of counterregulatory hormones, PAI-1 or Lp( a). Thus, the rapidly increased fibrinolytic activity after 2 h hyperi nsulinemia with maintained euglycemia can not be explained by the conc omitant changes in counterregulatory hormones. It is more likely that the decreased FFA and/or triglyceride levels play a role.