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 .
Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone.
BACKGROUND Troglitazone decreases insulin resistance and hyperglycemia in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) , but its effects on subjects without diabetes are not known . METHODS We performed oral and intravenous glucose-tolerance tests , studies with the euglycemic-hyperinsulinemic clamp , meal-tolerance tests , and 24-hour blood-pressure measurements at base line and after the administration of troglitazone , 200 mg orally twice daily , or placebo for 12 weeks in 18 nondiabetic obese subjects , 9 of whom had impaired glucose tolerance . RESULTS The mean ( + /- SD ) rates of glucose disposal increased from 4.7 + /- 1.7 to 6.0 + /- 1.7 mg per kilogram of body weight per minute ( P = 0.004 ) and from 9.0 + /- 1.8 to 9.9 + /- 1.3 mg per kilogram per minute ( P = 0.02 ) during insulin infusions of 40 and 300 mU per square meter of body-surface area per minute , respectively , in the troglitazone group . The insulin-sensitivity index , calculated from the results of intravenous glucose-tolerance tests , increased from 0.7 + /- 0.6 x 10(-4 ) to 1.6 + /- 0.9 x 10(-4 ) in subjects given troglitazone , and their glycemic response to oral glucose and to mixed meals decreased . The mean fasting plasma insulin concentration decreased by 48 percent ( P = 0.002 ) , and the plasma insulin response to oral glucose and mixed meals decreased by 40 and 41 percent , respectively . The changes were similar in the subjects with normal glucose tolerance and those with impaired glucose tolerance . Systolic and diastolic blood pressure decreased by 5 + /- 2 mm Hg ( P = 0.05 ) and 4 + /- 2 mm Hg ( P = 0.04 ) , respectively , after treatment with troglitazone . There were virtually no changes in the placebo group . CONCLUSIONS Troglitazone decreases insulin resistance and improves glucose tolerance in obese subjects with either impaired or normal glucose tolerance . The ability of troglitazone to reduce insulin resistance could be useful in preventing NIDDM
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 .