Revitalization of pioglitazone: The optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor

R. A. Defronzo, R. Chilton, L. Norton, G. Clarke, R. E.J. Ryder, M. Abdul-Ghani

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM.

Original languageEnglish (US)
Pages (from-to)454-462
Number of pages9
JournalDiabetes, Obesity and Metabolism
Issue number5
StatePublished - May 1 2016


  • SGLT2 inhibitor
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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