K Landin1, L Tengborn, U Smith. 1. Department of Medicine, Sahlgrenska Hospital, University of Göteborg, Sweden.
Abstract
OBJECTIVE: To study the effect of metformin and metoprolol CR on insulin sensitivity, blood lipids, fibrinolytic activity and blood pressure. DESIGN: A double-blind, placebo controlled, triple cross-over study with randomization to either metformin, 850 mg b.i.d., or metoprolol CR 100 mg o.d., or placebo for a period of 18 weeks. The glucose uptake was measured with the euglycaemic clamp technique after every 6 weeks' treatment period. Blood pressure and blood samples were taken every 3rd week. SUBJECTS:Eighteen non-obese men (53 +/- 6 years of age). RESULTS:Metformin decreased C-peptide (P < 0.02), FFA (P < 0.003), total and low-density lipoprotein cholesterol, tissue plasminogen activator antigen and the urinary potassium excretion (P < 0.05 for all), but not blood pressure compared to placebo. MetoprololCR reduced diastolic blood pressure and pulse rate; fasting free fatty acids and the urinary potassium increased (P < 0.05 for all). No effect of metformin or metoprolol CR was seen on the glucose disposal rate, blood glucose, plasma insulin, triglycerides, high-density lipoprotein cholesterol, lipoprotein(a), uric acid or plasminogen activator inhibitor 1 activity or antigen. The glucose uptake was not particularly decreased in these subjects. CONCLUSION: The study shows that metformin has some favourable effects on metabolism and that metoprolol CR is fairly neutral in this regard. The lack of effect of metformin on glucose disposal rate and blood pressure can be explained by the fact that the individuals studied were neither insulin resistant nor hypertensive. The data does not preclude an antihypertensive effect by treating a concomitant insulin resistance.
RCT Entities:
OBJECTIVE: To study the effect of metformin and metoprolol CR on insulin sensitivity, blood lipids, fibrinolytic activity and blood pressure. DESIGN: A double-blind, placebo controlled, triple cross-over study with randomization to either metformin, 850 mg b.i.d., or metoprolol CR 100 mg o.d., or placebo for a period of 18 weeks. The glucose uptake was measured with the euglycaemic clamp technique after every 6 weeks' treatment period. Blood pressure and blood samples were taken every 3rd week. SUBJECTS: Eighteen non-obesemen (53 +/- 6 years of age). RESULTS:Metformin decreased C-peptide (P < 0.02), FFA (P < 0.003), total and low-density lipoprotein cholesterol, tissue plasminogen activator antigen and the urinary potassium excretion (P < 0.05 for all), but not blood pressure compared to placebo. Metoprolol CR reduced diastolic blood pressure and pulse rate; fasting free fatty acids and the urinary potassium increased (P < 0.05 for all). No effect of metformin or metoprolol CR was seen on the glucose disposal rate, blood glucose, plasma insulin, triglycerides, high-density lipoprotein cholesterol, lipoprotein(a), uric acid or plasminogen activator inhibitor 1 activity or antigen. The glucose uptake was not particularly decreased in these subjects. CONCLUSION: The study shows that metformin has some favourable effects on metabolism and that metoprolol CR is fairly neutral in this regard. The lack of effect of metformin on glucose disposal rate and blood pressure can be explained by the fact that the individuals studied were neither insulin resistant nor hypertensive. The data does not preclude an antihypertensive effect by treating a concomitant insulin resistance.