Pioglitazone in Combination with Insulin—An Overview of Results from PROactive

Abstract

Pioglitazone provides one of several add-on therapy options for patients with unsatisfactory glycemic control treated with insulin. Although pioglitazone has the beneficial feature of low hypoglycemia risk, it has an overlapping adverse event profile with insulin in terms of edema (with the potential to exacerbate heart failure) and weight gain, leading to possible concern over their use in combination. Fortunately, subgroup analyses from the Prospective pioglitazone clinical trial in macrovascular events (PROactive) have provided valuable insights into the efficacy and safety profile of pioglitazone in patients on established insulin therapy. Pioglitazone improved glycemic control and lipids, while enabling patients to reduce their insulin requirements. With the combination, edema and weight were predictable with no excess exacerbation of heart failure. Importantly, pioglitazone had a good macrovascular safety profile (with a trend toward benefit), consistent with the overall population. This article provides an overview of the results from the insulin-treated subgroup in PROactive and highlights some of the clinical implications for pioglitazone–insulin combination therapy.