Sodium−glucose co-transporter-2 inhibitors or
gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with
type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that
gliflozins might modulate oxidative stress, platelet activation and
thrombus formation. We performed an interventional open-label single-arm before-after study in 32 T2D patients on top of their ongoing
metformin therapy. The population was divided into two groups: treatment with
GLP-1 receptor agonists (GLP-1RA, Group A) and
gliflozins (Group B). Oxidative stress, platelet activation and
thrombus growth were assessed before and after 15 days of treatment. Compared to the baseline,
gliflozins treatment significantly decreased sNOX2-dp (−45.2%, p < 0.001), H2O2 production (−53.4%, p < 0.001), TxB2 (−33.1%, p < 0.001), sP-
selectin (−49.3%, p < 0.001) and sCD40L levels (−62.3%, p < 0.001) as well as
thrombus formation (−32%, p < 0.001), whereas it potentiated
anti-oxidant power (HBA, +30.8%, p < 0.001). Moreover, a significant difference in oxidative stress, platelet activation and
thrombus formation across groups A and B was found. In addition, an in vitro study on stimulated platelets treated with
gliflozins (10−30 μM) showed a reduction in oxidative stress, platelet activation and
thrombus growth. Our results showed that
gliflozins have antiplatelet and antithrombic activity related to an NOX2 down-regulation, suggesting a new mechanism responsible for cardiovascular protection.