Pioglitazone: The forgotten, cost-effective cardioprotective drug for type 2 diabetes

Ralph A. DeFronzo, Silvio Inzucchi, Muhammad Abdulghani, Steven E. Nissen

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Type 2 diabetes individuals are at high risk for macrovascular complications: myocardial infarction, stroke and cardiovascular mortality. Recent cardiovascular outcome trials have demonstrated that agents in two antidiabetic classes (SGLT2 inhibitors and GLP-1 receptor agonists) reduce major adverse cardiovascular events. However, there is strong evidence that an older and now generically available medication, the thiazolidinedione, pioglitazone, can retard the atherosclerotic process (PERISCOPE and Chicago) and reduce cardiovascular events in large randomized prospective cardiovascular outcome trials (IRIS and PROactive). Pioglitazone is a potent insulin sensitizer, preserves beta-cell function, causes durable reduction in HbA1c, corrects multiple components of metabolic syndrome and improves nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Adverse effects (weight gain, fluid retention, fractures) must be considered, but are diminished with lower doses and are arguably outweighed by these multiple benefits. With healthcare expenses attributable to diabetes increasing rapidly, this cost-effective drug requires reconsideration in the therapeutic armamentarium for the disease.

Original languageEnglish
Pages (from-to)133-143
Number of pages11
JournalDiabetes and Vascular Disease Research
Issue number2
Publication statusPublished - 1 Mar 2019


  • cardiovascular disease
  • Pioglitazone
  • type 2 diabetes mellitus


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