Plasma lipid concentration and lipoprotein composition were studied before and after several months of glipizide treatment in 23 patients with non-insulin-dependent diabetes mellitus. The mean (+/- SEM) plasma glucose level fell 87 mg/dL, and the fall in plasma glucose concentration was correlated with a reduction in plasma triglyceride, very low-density lipoprotein triglyceride, cholesterol, and low-density lipoprotein cholesterol levels. Furthermore, there was a statistically significant increase in the plasma high-density lipoprotein cholesterol to total cholesterol ratio. Thus, improved diabetic control in patients treated with glipizide with non-insulin-dependent diabetes mellitus leads to changes in lipoprotein metabolism thought to be beneficial in terms of known cardiovascular risk factors.