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 .
Metformin improves peripheral but not hepatic insulin action in obese patients with type II diabetes.
UNLABELLED Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study . Metformin 0.5 g trice daily or placebo were given for 4 weeks . At the end of each period fasting and day-time postpr and ial values of plasma glucose , insulin , C-peptide and lactate were determined , and in vivo insulin action was assessed using the euglycemic clamp in combination with [3 - 3H]glucose tracer technique . Metformin treatment significantly reduced mean day-time plasma glucose levels ( 10.2 + /- 1.2 vs 11.4 + /- 1.2 mmol/l , P less than 0.01 ) without enhancing mean day-time plasma insulin ( 43 + /- 4 vs 50 + /- 7 mU/l , NS ) or C-peptide levels ( 1.26 + /- 0.12 vs 1.38 + /- 0.18 nmol/l , NS ) . Fasting plasma lactate was unchanged ( 1.57 + /- 0.16 vs 1.44 + /- 0.11 mmol/l , NS ) , whereas mean day-time plasma lactate concentrations were slightly increased ( 1.78 + /- 0.11 vs 1.38 + /- 0.11 mmol/l , P less than 0.01 ) . The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization ( 370 + /- 38 vs 313 + /- 33 mg.m-2.min-1 , P less than 0.01 ) , whereas insulin-mediated suppression of hepatic glucose production was unchanged . Also basal glucose clearance was improved ( 61.0 + /- 5.8 vs 50.6 + /- 2.8 ml.m-2.min-1 , P less than 0.05 ) , whereas basal hepatic glucose production was unchanged ( 81 + /- 6 vs 77 + /- 4 mg.m-2.min-1 , NS ) . CONCLUSIONS 1 ) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion . ( ABSTRACT TRUNCATED AT 250 WORDS
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 .