Blood glucose, lipoproteins, non-esterified fatty acids, fibrinogen and intermediary metabolites were measured in twenty-two diet failed maturity onset diabetics during a double blind crossover study of metformin (1.7 g/day) or clofibrate (2 g/day) therapy. Patients received combined therapy for a final two month period. Four patients had 12 hour metabolic profiles performed during each treatment period. A more significant improvement in fasting blood glucose and glycosuria occured with metformin and combined therapy. However, clofibrate and combined therapy significantly decreased total and low density lipoprotein cholesterol, total and very low density lipoprotein triglyceride and fibrinogen. Metabolic profiles demonstrated significant elevations of blood lactate and alanine with metformin treatment but these parameters returned to normal with combined therapy. Non-esterified fatty acids and glycerol were significantly lower during combined therapy compared with metformin or clofibrate alone. Despite the recent adverse report on clofibrate, this study indicates that the addition of clofibrate to metformin therapy may have advantages in the management of maturity onset diabetics.