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 .
Effects of metformin and rosiglitazone treatment on insulin signaling and glucose uptake in patients with newly diagnosed type 2 diabetes: a randomized controlled study.
The effect of metformin or rosiglitazone monotherapy versus placebo on insulin signaling and gene expression in skeletal muscle of patients with newly diagnosed type 2 diabetes was determined . A euglycemic-hyperinsulinemic clamp , combined with skeletal muscle biopsies and glucose uptake measurements over rested and exercised muscle , was performed before and after 26 weeks of metformin ( n = 9 ) , rosiglitazone ( n = 10 ) , or placebo ( n = 11 ) treatment . Insulin-mediated whole-body and leg muscle glucose uptake was enhanced 36 and 32 % , respectively , after rosiglitazone ( P < 0.01 ) but not after metformin or placebo treatment . Insulin increased insulin receptor substrate 1 ( IRS-1 ) tyrosine phosphorylation , IRS-1-associated phosphatidylinositol ( PI ) 3-kinase activity , and phosphorylation of Akt Ser473 and AS160 , a newly described Akt substrate that plays a role in GLUT4 exocytosis , approximately 2.3 fold before treatment . These insulin signaling parameters were unaltered after metformin , rosiglitazone , or placebo treatment . Expression of selected genes involved in glucose and fatty acid metabolism in skeletal muscle was unchanged between the treatment groups . Low-intensity acute exercise increased insulin-mediated glucose uptake but was without effect on insulin signaling . In conclusion , the insulin-sensitizing effects of rosiglitazone are independent of enhanced signaling of IRS-1/PI 3-kinase/Akt/AS160 in patients with newly diagnosed type 2 diabetes
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 .