Effect of Bezafibrate on Metabolic Profiles in Non-Insulin-Dependent Diabetes Mellitus

Abstract

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia secondary to increased hepatic glucose output and impaired extrahepatic insulin sensitivity. Many NIDDM patients also have raised serum triglyceride and low-density lipoprotein (LDL) cholesterol levels, which may require drug therapy, as well as increased plasma nonesterified fatty acid concentrations. Some hypolipidemic agents such as bezafibrate lower fatty acid levels as well as LDL cholesterol and triglycerides. It has been suggested that raised fatty acid levels may be responsible in part for the increased hepatic glucose output and insulin insensitivity of NIDDM. Several groups have therefore sought to examine the effects of fibrates on glycemic control in NIDDM. In our own studies, we used bezafibrate (200 mg t.i.d.) in a double-blind, placebo-controlled design for 3 months. Fasting blood glucose, serum insulin, C-peptide, plasma nonesterified fatty acids, blood lactate and alanine, serum triglycerides, and LDL cholesterol were all lowered. HbA1 showed no significant change. Meal hormone and metabolite profiles were all improved although this reflected mainly the lower premeal values. The results of our and other studies are sufficiently encouraging to suggest that bezafibrate could provide alternative first-line drug therapy in hyperlipidemic NIDDM patients when diet alone has failed.