Empagliflozin decreases the plasma concentration of plasminogen activator inhibitor-1 (PAI-1) in patients with type 2 diabetes: Association with improvement of fibrinolysis

Aims: Elevation of the plasma concentration of plasminogen activator inhibitor-1 (PAI-1), a rapid-acting inhibitor of fibrinolysis, is associated with development of vascular thrombotic diseases, including coronary artery disease and stroke. We investigated the effects of empagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on the plasma concentration of PAI-1 and fibrinolytic activity in patients with type 2 diabetes. Methods: In a randomized, active-controlled, open-label trial, 51 patients with type 2 diabetes were randomly allocated at a 2:1 ratio to receive empagliflozin (10 mg/day, n = 31) or standard therapy (n = 18) for 12 weeks. We measured the plasma concentrations of PAM and plasmin-alpha 2-antiplasmin complex (PAP) as indicators of fibrinolytic activity. Serum leptin and high-molecular weight (HMW) adiponectin were also measured. Results: In 49 patients who completed the trial, baseline plasma PAN showed a positive correlation with body weight, visceral fat area (VFA), gamma-glutamyltranspeptidase (GGT), leptin, and the platelet count, while it showed a negative correlation with HDL cholesterol and PAP. Body weight and VFA decreased significantly in the empagliflozin group, but not in the control group. The serum level of GGT showed a significant decrease at 12 weeks in the empagliflozin group, while it was unchanged in the control group. Serum HMW adiponectin increased significantly in the empagliflozin group. Plasma PAI-1 decreased significantly by 25% in the empagliflozin group, but not in the control group. In the empagliflozin group, the change of plasma PAI-1 was positively correlated with the changes of body weight and leptin, but was negatively correlated with the change of PAP. Conclusions: Empagliflozin reduced the plasma PAI-1 concentration through its synergistic actions of a glucose-lowering effect, VFA loss, and restoring the adipokine balance. (C) 2020 Elsevier Inc. All rights reserved.