Thiazolidinediones in type 2 diabetes: A cardiology perspective

OBJECTIVE: To examine the cardiovascular effects of thiazolidinediones (TZDs), discuss concerns regarding this drug class and its relation to heart failure (HF) and myocardial infarction (MI), and address the clinical implications of HF and MI. DATA SOURCES: Literature was accessed through MEDLINE (1979-April 2008) using the search terms type 2 diabetes mellitus, thiazolidinediones, cardiovascular events, heart failure, myocardial infarction, and edema. Reviews, meta-analyses, clinical trials, observational studies (case-control, cohort), and descriptive studies (case reports, case series) were included. STUDY SELECTION AND DATA EXTRACTION: All articles that were written in English and identified from the data sources were reviewed. DATA SYNTHESIS: The American Diabetes Association recommends metformin as first-line therapy for type 2 diabetes, with the subsequent addition of a TZD, sulfonylurea, or insulin if the target is not met. Beyond glucose lowering, TZDs improve various factors associated with cardiovascular risk. Whether the effects translate into beneficial cardiovascular outcomes is controversial. In PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events), pioglitazone did not produce a significant reduction in the primary endpoint that included a composite of coronary and vascular deaths, but the secondary composite endpoint of all-cause mortality, MI, or stroke was significantly reduced. Concerns related to HF have led to warnings in the labeling of TZDs. The drugs are contraindicated in patients with New York Heart Association Class III or IV HF. Rosiglitazone, but not pioglitazone, is associated with an increased risk of myocardial ischemic events, although the absolute magnitude is extremely small. CONCLUSIONS: Although the glycemic efficacy of TZDs is comparable to that of metformin, adverse effects and higher costs make TZDs less appealing for initial therapy. Among the TZDs, pioglitazone should be considered based on cardiovascular safety data. In combination with metformin, pioglitazone may be particularly beneficial for patients with diabetes and metabolic syndrome. For patients on rosiglitazone who are achieving glycemic goals and tolerating the therapy without apparent complications, rosiglitazone may be continued.