Twenty-seven patients with non-insulin-dependent diabetes mellitus and fasting plasma glucose values greater than 140 mg/dl began glyburide therapy. After entry into the study, patients were classified into three phenotypes on the basis of their initial lipoprotein profile: type IV, mixed, and normal. Glyburide lowered plasma glucose and raised plasma insulin concentrations in non-insulin-dependent diabetes mellitus. Patients with type IV hyperlipoproteinemia had higher fasting free insulin concentrations before and after therapy than patients without hyperlipoproteinemia and may have a slightly reduced hypoglycemic response to glyburide therapy. The drug caused a significant reduction in very-low-density lipoprotein cholesterol in patients with non-insulin-dependent diabetes mellitus and type IV hyperlipoproteinemia, along with a variable change in high-density lipoprotein cholesterol, independent of its effect on plasma glucose. © 1985 Technical Publishing.