Objectives: Elevation of the plasma concentration of plasminogen activator inhibitor-1 (PAI-1), a rapid-acting inhibitor of fibrinolysis, is associated with development of cardiovascular diseases. We investigate the effects of empagliflozin, an 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 PAI-1 and plasmin-α2-antiplasmin complex (PAP) as indicators of fibrinolytic activity. Serum leptin and HMW adiponectin were also measured.
Results: Body weight and visceral fat decreased in the empagliflozin group, but not in the control group. The serum level of γ-GTP 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, weight loss, and restoring the adipokine balance. The beneficial effects of empagliflozin on fibrinolysis by decreasing circulating PAI-1 may be associated with improvement of vascular thrombotic outcomes in patients with type 2 diabetes. (Clinical trial registry: UMIN000025418).
T. Niitani: None. S. Sakurai: None. T. Jojima: None. T. Iijima: None. T. Tomaru: Research Support; Self; Merck & Co., Inc., Teijin Pharma Limited. I. Usui: None. Y. Aso: None.