PO32 | Effect of the sodium-glucose co-transporter-2 (SGLT2) inhibitors on platelet activation and lipid peroxidation: results of a pilot study

P.G.M. Simeone¹, R. Liani¹, M. Alfonsetti¹, B. Cancelli¹, M. Frezza¹, G. Raggiunti¹, S. Zeeba², F. Cipollone¹, G. Renda², F. Santilli¹ | ¹Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology, University of Chieti; ²Department of Neuroscience, Imaging and Clinical Sciences, G. D’Annunzio University of Chieti-Pescara; ³University Cardiology Division, Heart Department, Policlinico SS Annunziata, Chieti, Italy

Background and Aim: Sodium–glucose co-transporter-2 inhibitors (SGLT2is), or gliflozins, represent the most recent class of antihyperglycemic agents and have been shown to confer significant cardioprotective effects in patients with and without type 2 diabetes (T2D). Thromboxane (TX)-dependent platelet activation and lipid peroxidation—reflected in vivo by urinary excretion of 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α—play a critical role in the development of atherothrombosis in type 2 diabetes mellitus (T2DM). Since oxidative stress and platelet activation play a key role in the development of atherothrombotic complications, we hypothesized that gliflozins may exert modulatory effects on these pathways.

Methods: We conducted a pilot prospective observational study in diabetic patients naïve to gliflozins, in whom these drugs are prescribed according to clinical indications, before–after interventional study in 20 patients with T2D receiving background therapy with metformin. Oxidative stress and platelet activation, were evaluated at baseline and after 15 days of treatment.

Results: In patients treated with gliflozins, we observed significant reductions markers of platelet activation and oxidative stress: 11-dehydro-TXB2 (p=0.032) (Figure 1, panel A), 8-iso-prostaglandin (PG)F2α (p=0.026) (Figure 1, panel B). Delta 8-iso-prostaglandin (PG)F2α was directly correlated with delta 11-dehydro-TXB2 (rho=0.7639, p <0.001) (Figure 1, panel C).

Conclusions: These findings suggest that gliflozins possess antiplatelet and antioxidants properties, potentially mediated through 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α downregulation. This mechanism may contribute to the cardiovascular benefits observed with SGLT2i therapy in patients with and T2D.