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 .
Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.
Pioglitazone increases the insulin sensitivity of peripheral tissues and may provide an alternative first-line treatment for type 2 diabetes . This study compared metabolic control in drug-naive type 2 diabetes patients given either pioglitazone or metformin .  Eleven hundred and ninety-nine patients with poorly controlled type 2 diabetes mellitus [ glycosylated hemoglobin ( HbA1c ) , 7.5 - 11 % ; normal , 4.3 - 6.1 % ] were r and omized to receive either pioglitazone ( < or = 45 mg/d ) or metformin ( < or = 850 mg , three times daily ) . HbA1c , fasting plasma glucose ( FPG ) , insulin levels , total cholesterol ( TC ) , high density lipoprotein cholesterol ( HDL-C ) , low density lipoprotein cholesterol , triglycerides , free fatty acids , and urinary albumin/creatinine ratio were measured . Mean HbA1c decreased in both treatment groups from baseline to wk 52 ( -1.4 % and -1.5 % ) . Significantly greater mean reductions in FPG were observed in the pioglitazone group ( -45.0 mg/dl ; -2.5 mmol/liter ) than in the metformin ( -39.6 mg/dl ; -2.2 mmol/liter ) group ( P = 0.016 ) . Favorable changes in triglycerides and HDL-C were more pronounced with pioglitazone . Although low density lipoprotein cholesterol and TC levels increased with pioglitazone , TC/HDL-C ratios decreased similarly with both treatments . The urinary albumin/creatinine ratio was reduced by 19 % with pioglitazone treatment , but remained unchanged with metformin therapy ( -1 % ; P = 0.002 ) . There was an increase in body weight of 1.9 kg in the pioglitazone group and a decrease of 2.5 kg in the metformin group . The overall frequency of adverse events was similar between treatment groups , but adverse event profiles were different between treatment groups . HbA1c reduction is similar after pioglitazone and metformin monotherapies , but differences in FPG , plasma lipids , and adverse effects between the two compounds may influence decision-making in individual prescribers
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 .