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 .
Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes.
Rosiglitazone , a thiazolidinedione , enhances peripheral insulin sensitivity in patients with type 2 diabetes . Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance , the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes . Therefore , 45 patients with newly diagnosed or diet-treated type 2 diabetes were r and omized for treatment with rosiglitazone ( 4 mg b.i.d . ) , metformin ( 1 g b.i.d . ) , or placebo in a 26-week double-blind trial . Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography ( PET ) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period . Rosiglitazone ( P < 0.05 ) and metformin ( P < 0.0001 ) treatment lowered the mean glycosylated hemoglobin . The skeletal muscle glucose uptake was increased by 38 % ( P < 0.01 ) and whole-body glucose uptake by 44 % in the rosiglitazone group . Furthermore , the exercise-induced increment during insulin stimulation was enhanced by 99 % ( P < 0.0001 ) . No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group . In conclusion , rosiglitazone but not metformin 1 ) improves insulin responsiveness in resting skeletal muscle and 2 ) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes . Our results suggest that rosiglitazone improves synergic action of insulin and exercise
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 .