Effects of dapagliflozin in combination with insulin on cytochrome P450 activities in a diabetes type 1 rat model.

Abstract

Previous studies reported that diabetes alters the activities of hepatic cytochrome P450 (CYP) enzymes, which, in turn, affects the disposition of some drugs. We herein examined and compared the effects of the combination of dapagliflozin with a low insulin dose, a full dose of insulin alone, and dapagliflozin alone for 3 and 8 weeks on CYP activities in a diabetes type 1 rat model. We induced type 1 diabetes in rats using a single intraperitoneal injection of 60 mg/kg streptozotocin (STZ). Daily treatment with the full dose of insulin alone, dapagliflozin alone, or dapagliflozin in combination with a low dose of insulin was then initiated. STZ-induced rats developed marked hyperglycemia and altered CYP2E activities. Dapagliflozin in combination with a low dose of insulin stabilized hyperglycemia and CYP1A, 2D, 2E and 3A activities. However, dapagliflozin alone did not improve blood glucose levels or CYP activities. These results suggest that the effects of dapagliflozin in combination with a low dose of insulin are similar to those of a full dose of insulin, and stabilize CYP activities in type 1 diabetes.