Withdrawal of pioglitazone in patients with type 2 diabetes mellitus

Abstract

The remodelling of the adipose tissue by pioglitazone may be associated with the sustained therapeutic effects. We studied the effects of withdrawal of pioglitazone after 3-month treatment on glucose, lipid and high-molecular weight (HMW) adiponectin levels as well as liver function in patients with type 2 diabetes mellitus. Forty-nine Japanese patients with type 2 diabetes mellitus were randomly assigned into the withdrawal group after 3-month treatment with pioglitazone (15 or 30 mg daily) and the non-withdrawal group. Three-month treatment with pioglitazone improved glycaemic control, homeostasis model assessment for insulin resistance (HOMA), dyslipidaemia and liver function tests in association with a marked increase in serum HMW adiponectin level. Three months later after the withdrawal of pioglitazone, however, fasting plasma glucose and HOMA increased, whereas serum HMW adiponectin decreased to the pretreatment levels. Dyslipidaemia also returned to the pretreatment level. On the other hand, liver enzymes at 3 months after the withdrawal remained lower after a mild rebound. In addition, the bone formation marker, serum bone-specific alkaline phosphatase, was significantly reduced by pioglitazone treatment in post-menopausal women. The present study suggests that 3-month treatment with pioglitazone has no sustained beneficial effects except in liver function tests in patients with type 2 diabetes mellitus.