Can combination therapy with insulin and metformin improve metabolic function of the liver, in type I diabetic patients? An animal model study on CYP2D1 activity.

ABSTRACT

INTRODUCTION: Changes in hepatic clearance and CYP2D1 activity after combination therapy with insulin and metformin in type-1 diabetes and insulin administration in type-2 diabetes was assessed in an animal model. METHODS: Ten male Wistar rats were divided into two groups. Seven days after induction of diabetes, in treatment groups, type-1 diabetic rats received insulin plus metformin, and type-2 diabetic rats received insulin daily for 14 days. On day 21, rats were subjected to liver perfusion using Krebs-Henseleit buffer containing dextromethorphan as a CYP2D1 probe. Perfusate samples were analyzed by HPLC-FL. RESULTS: The average metabolic rate of dextromethorphan and hepatic clearance changed from 0.012 ± 0.004 and 6.3 ± 0.1 ml/min in the control group to 0.006 ± 0.001 and 5.2 ± 0.2 ml/min in the untreated type-1 diabetic group, and 0.008 ± 0.003 and 5 ± 0.6 ml/min in the untreated type-2 diabetic rats [1]. In the present study, metabolic rate and hepatic clearance changed to 0.0112 ± 0.0008 and 6.2 ± 0.1 ml/min in the type-1 diabetic group treated with insulin plus metformin, and 0.0149 ± 0.0012 and 6.03 ± 0.06 ml/min in the insulin-receiving type-2 diabetic rats. CONCLUSIONS: Administration of insulin plus metformin in type-1 diabetes could modulate the function of CYP2D1 to the observed levels in the control group and made it clearer to predict the fate of drugs that are metabolized by this enzyme. Moreover, good glycemic control with insulin administration has a significant effect on the balance between hepatic clearance and CYP2D1 activity in type-2 diabetes.