Safety and Efficacy of Pioglitazone/Metformin Combination Therapy in Treatment of Type 2 Diabetes: A Rationale for Earlier Use

Although multiple new agents for the management of diabetes have become available in the past decade, less than 50% of diabetics in the United States have Hgb A-1-C levels below 7.0% and far fewer at the newer more stringent targets of 6.0% to 6.5%. It has become increasingly clear that the course of Type 2 diabetes is marked by progressive loss of beta-cell function in the setting of relatively fixed insulin resistance. However, treatment algorithms are based on initial monotherapy, usually with metformin, and only move to combination or add-on therapy when treatment has failed and disease has progressed. Few therapeutic agents address both insulin resistance and beta cell function, and no monotherapeutic agent fully addresses any physiologic defect. Metformin, a well-established therapy for diabetes is effective in reducing hepatic and to a lesser extent muscle insulin resistance primarily through AMP-kinase activation, but has only modest effects on long-term beta-cell function. Pioglitazone, an agent ...