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

Figure 3

Role of GLP-1RA in obesity, adipose tissue inflammation, and cardiac and kidney disease. In obesity, glucagon-like peptide 1 agonist (GLP-1RA) effects are related to its capacity to penetrate the blood-brain barrier and the presence of the glucagon-like peptide 1 receptor (GLP-1R) in different brain regions, resulting in appetite reduction, increase in satiety, and abdominal fullness and a decrease in food cravings. This, in turn, favors a weight loss of 2 to 8 kg on average. In the kidneys, an antioxidant and anti-inflammatory role has been reported. Via the activation of the Sirt1/AMPK/PGC1α signaling pathway, it partially restores the function of renal mitochondria and decreases lipid deposition and inflammation in the kidneys. Lastly, its role has been proven in the mitigation of inflammation since it favors macrophage polarization and adiponectin production while promoting mitochondrial biogenesis and adequate function, as well as adipose tissue browning. GLP-1RA: glucagon-like peptide 1 agonists; GLP-1R: glucagon-like peptide 1 receptor; SIRT1: sirtuin 1; AMPK: AMP-activated protein kinase; PGC1α: Pparg coactivator 1 alpha; WAT: white adipose tissue; ANP: atrial natriuretic peptide.