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

Diabetes Obes Metab. 2016 May;18(5):454-62. doi: 10.1111/dom.12652. Epub 2016 Apr 6.

Abstract

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.

Keywords: SGLT2 inhibitor; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Angiopathies / prevention & control
  • Diabetic Cardiomyopathies / prevention & control
  • Drug Therapy, Combination
  • Evidence-Based Medicine*
  • Glucosides / adverse effects
  • Glucosides / therapeutic use
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Membrane Transport Modulators / adverse effects
  • Membrane Transport Modulators / therapeutic use*
  • Pioglitazone
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / therapeutic use*

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Membrane Transport Modulators
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiazolidinediones
  • empagliflozin
  • Pioglitazone