Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class 
that works through activation of the peroxisome proliferator-activated nuclear 
receptor. It improves insulin sensitivity in peripheral tissues and effectively 
lowers blood glucose in patients with type 2 diabetes. Metformin is a 
dimethyl-biguanide, also used in type 2 diabetes, that lowers fasting blood 
glucose primarily by decreasing hepatic glucose output. Rosiglitazone and 
metformin reduce plasma glucose concentrations via different mechanisms and thus 
could potentially be used in combination to optimize glycemic control. This 
study evaluated the effects of the coadministration of these two agents on the 
pharmacokinetics of both rosiglitazone and metformin. Sixteen male volunteers 
(22-55 years old) received oral metformin (500 mg every 12 hours), rosiglitazone 
(2 mg every 12 hours), or the combination each for 4 days. Plasma collected on 
day 4 of each regimen was assayed for rosiglitazone and metformin 
concentrations. Oral doses of rosiglitazone and metformin were safe and well 
tolerated when administered alone or in combination. There were no clinically 
significant episodes of hypoglycemia or increased blood lactic acid levels 
following treatment with any regimen. Coadministration of rosiglitazone and 
metformin had no significant effects on the steady-state pharmacokinetics 
(AUC(0-12 h), Cmax, tmax, or t1/2) of either drug. The authors conclude that 
rosiglitazone can be safely administered with metformin and, due to the 
different mechanisms of action of these agents, may offer a therapeutic 
advantage in patients with type 2 diabetes mellitus.