Short-term effects of metformin in type 2 diabetes

Background: Although metformin is widely used in the management of type 2 diabetes, its mechanism(s) of action is not fully known, and there have been remarkably few reports on short-term effects of the drug. Here, we examined the early effects on glucose and lipid metabolism and on certain adipose tissue and inflammatory markers during treatment for 28 days. Methods: Twenty-one patients were randomized to metformin (n = 16) or placebo (n = 5) and studied at baseline, 1, 2 and 4 weeks with blood sampling and oral glucose tolerance tests (OGTT). The active group received 500 mg metformin daily in the first week, 500 mg twice daily during week 2 and 1000 mg twice daily during weeks 3 and 4. Results: After 7 days of treatment, a reduced area under curve (AUC) for glucose at OGTT with no change in AUC for insulin levels was observed compared to baseline. Insulin sensitivity, as derived from the OGTT by Gutt's index, was increased. Reductions in fasting plasma glucose, total cholesterol and low-density lipoprotein cholesterol appeared after 14 days, and reductions in triglycerides, plasminogen activator inhibitor-1 (PAI-1) and leptin after 28 days of treatment. There were no changes in body weight, adiponectin or C-reactive protein. Compared with placebo, the changes between day 0 and day 28 differed significantly with regard to AUC for glucose at OGTT and Gutt's index, and showed strong trends for PAI-1 and leptin. Conclusions: The data demonstrate that in type 2 diabetes, metformin rapidly affects glucose handling without changing the concentrations of insulin. Reductions in PAI-1 and leptin levels indicate that the early effects of metformin involve also the adipose tissue.