Effect of phenformin on lipid transport in hypertriglyceridemia

The effect of phenformin on lipid metabolism was studied in nine hypertriglyceridemic subjects consuming isocaloric liquid formula diets. On a fat-free, 85% carbohydrate hydrate diet, phenformin reduced plasma triglyceride, cholesterol, and free fatty acid levels, the mean decreases being 14%, 13%, and 16%, respectively. The predominant effect of the drug was on very low density lipoprotein levels, with no change in low density lipoproteins. Plasma triglyceride and cholesterol levels were also reduced in the majority of subjects on a diet containing 40% of calories as fat and 45% as carbohydrate, but phenformin did not have any effect on the carbohydrate induction of triglyceride elevation. Basal insulin levels were reduced by the drug in all subjects (mean change, ?23%) and fasting glucose levels were lowered in the majority. The plasma lipolytic rate measured on endogenous substrate during a prolonged heparin infusion on the fat-free diet was reduced by phenformin (mean change, ?15%), although postheparin lipolytic activity on an artificial substrate was unchanged. Free fatty acid turnover, measured during the same procedure, fell in parallel with the fatty acid levels (mean change, ?27%). It is proposed that phenformin lowers plasma triglyceride levels in most subjects by reducing endogenous triglyceride production, and that the effects of the drug on glucose, insulin, and free fatty acid homeostasis contribute to this action. It is suggested that in some subjects the drug may also impair triglyceride clearance from plasma, and that this may account for the variable therapeutic response, since in three subjects phenformin did not decrease triglyceride levels on both diets.