SGLT2i and GLP-1RA in Cardiometabolic and Renal Diseases: From Glycemic Control to Adipose Tissue Inflammation and Senescence

Figure 2

Role of SGLT2i in obesity, adipose tissue inflammation, and cardiac and kidney disease. In obesity, these drugs modify the insulin : glucagon ratio, where glucagon increases, favoring lipolysis and lipid oxidation, while insulin decreases, causing an increase in endogenous glucose production from amino acids, favoring the process of lipolysis even more. Also, they attenuate the hemodynamic/neurohormonal mechanism in the kidney with positive changes of glomerular filtration rate (GFR), the tubular transport toil, and oxygen consumption. Ultimately, they have a role in the mitigation of inflammation decreasing the recruitment and accumulation of T cells and M1 macrophages, increasing the polarization of M2 macrophages, which release anti-inflammatory cytokines while activating adrenergic receptors in adipocytes, producing thermogenesis by the expression of uncoupling protein (UCP1). Furthermore, they increase adiponectin expression, which promotes the downregulation of SGLT2 and subcutaneous white adipose tissue (WAT) browning by stimulating the proliferation of M2 macrophages. SGLT2i: sodium-glucose cotransporter 2 inhibitors; GFR: glomerular filtration rate; UCP: uncoupling proteins; WAT: white adipose tissue.