The primary goal of the present study was to examine the effects of improved glycaemic control associated with glipizide treatment on postprandial lipaemia in non-insulin-dependent diabetic patients. The metabolism of triglyceride-rich lipoproteins of intestinal origin was assessed by measuring the retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20-400 lipoprotein fractions. Fasting plasma glucose concentrations (14.5 +/- 0.5 vs 9.0 +/- 0.5 mmol/l), glycated haemoglobin levels (13.1 +/- 0.6 vs. 9.7 +/- 0.6%), and daylong plasma glucose concentrations were all significantly lower after glipizide treatment (p < 0.001). The improvement in glycaemic control was associated with increases in insulin-mediated glucose uptake (p < 0.001) and plasma post-heparin lipoprotein and hepatic lipolytic activities (p < 0.02). Both fasting plasma triglyceride (3.09 +/- 0.51 vs 2.37 +/- 0.34 mmol/l), and postprandial triglyceride concentrations (p < 0.05-0.001) were lower following glipizide treatment, associated with a significant fall in retinyl palmitate content in all three lipoprotein fractions (p < 0.02-0.001), with the most substantial decrease seen in the Sf20-400 fraction. These data indicate that glipizide-induced improvement in glycaemic control was associated with changes in the metabolism of triglyceride-rich lipoproteins of intestinal origin that would be anticipated to reduce risk of coronary heart disease in non-insulin-dependent diabetic patients.