Practice Update: DIABETES

MY PERSPECTIVE 20

A resurgence of interest in pioglitazone? By Richard E Pratley MD

Dr Pratley serves as the Medical Director of the Florida Hospital Diabetes Institute, Senior Investigator and Diabetes Program Lead at the Translational Research Institute for Metabolism and Diabetes, and Adjunct Professor at the Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Florida.

For many years, thiazolidinedione (TZD) drugs such as pioglitazone and rosiglitazone occupied a prominent place in the treatment of type 2 diabetes. A meta-analysis by Nissen and Wolski in 2007 that suggested an increased risk of myocardial infarction and death in patients treated with rosiglitazone led to heightened scrutiny of the entire TZD class. 1 Two papers published in the last year and featured in PracticeUpdate suggest that it may be time to reconsider the use of TZDs, and pioglitazone in particular. Dr Pratley writes. T hey uniquely targeted insu- lin resistance, one of the primary pathophysiologic abnormalities

and Management Strategy (REMS) for rosiglitazone mandated by the FDA was dramatic. Use of the entire class, and especially rosiglitazone, fell dramatically. Concerns about the safety of the class were fueled by observational reports suggesting an increased risk of bladder cancer with pioglitazone and an increased risk of bone fracture with both drugs. In the fullness of time, a better picture of the actual risks of these drugs has developed. Now, the available data do not suggest an increased risk of myocardial infarction and death with rosiglitazone, and the FDA has removed its REMS. There also does not appear to be an increased risk of bladder cancer with pioglitazone. Nevertheless, uti- lization of these agents for the treatment of type 2 diabetes remains low. In the first study, Cusi and colleagues performed a randomized, double-blind, placebo-controlled trial of pioglitazone for

contributing to hyperglycemia in type 2 dia- betes, and consequently could be used to good effect in combination with other agents. They were effective at lowering glucose and A1c, and the improvement in glycemia was durable over a period of years. Importantly, because they did not enhance insulin secretion, they were asso- ciated with a low risk of hypoglycemia. Known risks associated with TZDs included weight gain and a propensity to cause fluid retention, edema, and, in a small number of patients, heart failure; but, in general, these risks could be managed by carefully selecting and closely monitoring patients. Although similar analyses did not indicate that pioglitazone was associated with the same risk, the impact of this general con- cern and the subsequent Risk Evaluation

PRACTICEUPDATE DIABETES