To investigate whether the lowering of triglyceride levels has beneficial effects on glucose metabolism, we studied 13 nondiabetic men with combined hyperlipidemia (phenotype IIB) before and after 2 months of treatment with a slow-release formulation of bezafibrate (400 mg daily). The rates of whole body glucose disposal were quantitated by the euglycemic hyperinsulinemic clamp technique (insulin infusion rate of 80 mU/m2/min). In an oral glucose tolerance test, fasting glucose level decreased slightly (5.0 +/- 0.2 versus 4.8 +/- 0.2 mmol/L; p < 0.05) during bezafibrate treatment. Glucose and insulin levels after an oral glucose load remained unchanged. Rates of whole body glucose disposal did not change during bezafibrate treatment (39.5 +/- 3.3 mumol/kg/min before treatment versus 40.6 +/- 2.7 mumol/kg/min after treatment; difference not significant). Basal hepatic glucose output also remained unchanged (8.2 +/- 0.2 mumol/kg/min before treatment versus 8.3 +/- 0.2 mumol/kg/min after treatment; difference not significant). Our findings show that bezafibrate has a triglyceride-lowering effect without any significant influence on insulin sensitivity.