title: Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor.
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.
authors.affiliation: Diabetes Division, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: DeFronzo
authors.affiliation: Cardiology Division, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Chilton
authors.affiliation: Diabetes Division, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.affiliation: Diabetes Division and Department of Radiology, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Clarke
authors.affiliation: Diabetes and Endocrine Unit, City Hospital, Birmingham, UK.
authors.forename: R E J
authors.initials: RE
authors.lastname: Ryder
authors.affiliation: Diabetes Division, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Abdul-Ghani
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000517:prevention & control; D058065:Diabetic Cardiomyopathies / Q000517:prevention & control; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D005960:Glucosides / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D049990:Membrane Transport Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D000077205:Pioglitazone; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D049990:Membrane Transport Modulators; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D045162:Thiazolidinediones; C570240:empagliflozin; D000077205:Pioglitazone
keywords: SGLT2 inhibitor; type 2 diabetes