Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013

Abstract

An updated algorithm for the initiation and adjustment of therapy for the management of hyperglycemia has been published as a position statement of the American Diabetes Association and European Association for the Study of Diabetes (32). According to this position statement, "pioglitazone appeared to have a modest benefit on CV events as a secondary outcome in one large trial involving patients with overtmacrovascular disease." In the proposed algorithm, pioglitazone monotherapy can be considered an alternative to metformin monotherapy if metformin cannot be used (not tolerated or is contraindicated), as a combination therapy if monotherapy with metformin alone does not achieve/maintain an HbA1c target, or a triple combination therapy, provided that oral agents with complementary mechanisms of action are used. Thus, pioglitazone remains an effective and useful antidiabetes drug with a unique insulin-sensitizing action. However, the clinical use of pioglitazone is currently under scrutiny because of safety issues and because of the availability of newer drugs (DPP-4 inhibitors, glucagonlike peptide-1 receptor agonists, and sodium glucose cotransporter 2 inhibitors). None of these newer drug classes target insulin resistance, however. At the moment, the most insulinresistant patientsdidentifiable by an increased waist circumference, low HDL cholesterol level, and fatty liverdmay be the best candidates for treatment with pioglitazone. In addition, patients with a high risk or history of CVD are also likely to benefit from pioglitazone. It is our belief that pioglitazone represents an important therapeutic option in people with T2DM and that more commonly used regimens are both less effective and more likely to result in worse safety outcomes. So, to answer our original question: yes, we still need pioglitazone for the treatment of T2DM. © 2013 by the American Diabetes Association.