#4581 EVALUATION OF THE BENEFICIAL EFFECTS OF SGLT2 INHIBITORS AND GLP-1 RECEPTOR AGONIST ON TOP OF RAS BLOCKADE IN EXPERIMENTAL DIABETIC NEPHROPATHY

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) some glucagon-like-1 receptor agonists (GLP1-RA) have demonstrated to delay diabetic nephropathy (DN) progression. Potentially, the combination of these two therapeutic approaches on top standard care with renin angiotensin system (RAS) blockers could exert additive cardiorenal protection in milieu. The present study aimed evaluate protective effects SGLT2i GLP1-RA RAS blockade versus monotherapies experimental diabetes. Method Twelve weeks old male female uninefrectomized (UNx) db/db mice were treated for 8 an (empagliflozin, 10 mg/Kg/day five days a week) and/or (semaglutide, 10.0 nmol/kg twice per blocker (ramipril, mg/Kg/day). Vehicle-treated UNx non-diabetic (db/m) included as controls. During experiment weight, food water intake, blood glucose, pressure (BP) glomerular filtration rate (GFR) measured. Kidney heart collected at end experiment. Results vehicle-treated showed increased body intake glucose compared db/m (Fig. 1A, B C, p = 0.03, p<0.001 p<0.0001, respectively). GFR slope (ΔGFR, difference between final basal GFR) was also significantly higher vs 1D, 0.02), typical feature incipient DN. All treatments decreased systolic diastolic BP due its ramipril component 1E). Further, both empagliflozin semaglutide (alone or combined) lowered 1C, vehicle all cases) but maximized this effect. Food combined empagliflozin) 1B) although no differences weight noted untreated 1A). A trend towards ΔGFR decline observed 1D). Finally, not kidney lower 1F). Conclusion Our preliminary results show that addition therapy synergic hypoglycemic effects. more research is needed, trended ameliorate hyperfiltration DN mouse model which suggests beneficial