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 .
A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients.
Troglitazone and metformin lower glucose levels in diabetic patients without increasing plasma insulin levels . We compared the insulin sparing actions of these two agents and their effects on insulin sensitivity and insulin secretion in 20 type 2 diabetic patients . To avoid the confounding effect of improved glycemic control on insulin action and secretion , patients were first rendered euglycemic with 4 weeks of continuous subcutaneous insulin infusion ( CSII ) before r and omization to CSII plus troglitazone ( n = 10 ) or CSII plus metformin ( n = 10 ) ; euglycemia was maintained for another 6 - 7 weeks . Insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp 1 ) at baseline , 2 ) after 4 weeks of CSII , and 3 ) after CSII plus either troglitazone or metformin . The 24-h glucose , insulin , and C-peptide profiles were performed on the day before the second and third glucose clamps . Good glycemic control was achieved with CSII alone and was maintained with CSII plus an oral agent ( mean 24-h glucose : troglitazone , 6.2+/-0.6 mmol/l ; metformin , 6.2 + /-0.3 mmol/l ) . Insulin requirements decreased 53 % with troglitazone compared with CSII alone ( 48+/-4 vs. 102+/-13 U/day , P < 0.001 ) , but only 31 % with metformin ( 76+/-13 vs. 110+/-18 U/day , P < 0.005 ) . The 24-h C-peptide profiles were similar . Normal fasting hepatic glucose output was maintained with both agents despite lower insulin levels than on CSII alone . Insulin sensitivity did not change significantly with CSII alone or with CSII plus metformin , but improved 29 % with CSII plus troglitazone ( P < 0.005 vs. CSII alone ) and was then 45 % higher than in the CSII plus metformin patients ( P < 0.005 ) . In conclusion , metformin has no effect on insulin-stimulated glucose disposal independent of glycemic control in type 2 diabetes . Troglitazone ( 600 mg/day ) has greater insulin-sparing effects than metformin ( 1,700 mg/day ) in CSII-treated euglycemic patients . This is probably explained by the peripheral tissue insulin-sensitizing effects of troglitazone
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 .