Results Both TZDs and metformin  enhance insulin suppression of endogenous glucose production and fasting plasma glucose clearance .
TZDs , but not metformin , also improve insulin-mediated glucose uptake at all insulin levels .
Conclusions /interpretationIn patients with type 2 diabetes , metformin improves fasting hepatic insulin sensitivity and glucose clearance ; TZDs improve fasting hepatic insulin sensitivity and glucose clearance , and potentiate glucose disposal under insulinised conditions
Aims /hypothesisInsulin resistance , which manifests itself as endogenous glucose overproduction and reduced insulin-mediated glucose uptake , is a core defect in type 2 diabetes .
Metformin and the peroxisome proliferator-activated receptor-γ agonists , the thiazolidinediones ( TZDs ) , both lower glucose , although their mechanism of action is still subject to debate .
This review analyses the evidence relevant to these mechanisms in vivo .
Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes.
Pioglitazone , a thiazolidinedione , improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes , whereas metformin , a biguanide , exerts its effect primarily by decreasing hepatic glucose output . In the first head-to-head , double-blind clinical trial comparing these two oral antihyperglycemic medications ( OAMs ) , we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy . Subjects were r and omized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg ( 77 % of pioglitazone patients ) and 2550 mg ( 73 % of metformin patients ) , as indicated , to achieve fasting plasma glucose levels of less than 7.0 mmol/liter ( 126 mg/dl ) . Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose . At endpoint , pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity , as determined by reduction of fasting serum insulin ( P = 0.003 ) and by analysis of homeostasis model assessment for insulin sensitivity ( HOMA-S ; P = 0.002 ) . Both OAM therapies were well tolerated . Therefore , pioglitazone and metformin are equally efficacious in regard to glycemic control , but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action . The more pronounced improvement in indicators of insulin sensitivity by pioglitazone , as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive , may be of interest for further clinical evaluation
Results Both TZDs and metformin  enhance insulin suppression of endogenous glucose production and fasting plasma glucose clearance .
TZDs , but not metformin , also improve insulin-mediated glucose uptake at all insulin levels .
Conclusions /interpretationIn patients with type 2 diabetes , metformin improves fasting hepatic insulin sensitivity and glucose clearance ; TZDs improve fasting hepatic insulin sensitivity and glucose clearance , and potentiate glucose disposal under insulinised conditions
Aims /hypothesisInsulin resistance , which manifests itself as endogenous glucose overproduction and reduced insulin-mediated glucose uptake , is a core defect in type 2 diabetes .
Metformin and the peroxisome proliferator-activated receptor-γ agonists , the thiazolidinediones ( TZDs ) , both lower glucose , although their mechanism of action is still subject to debate .
This review analyses the evidence relevant to these mechanisms in vivo .