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Activation of the glucagon-like peptide-1 receptor (GLP-1R) potentiates the exchange protein directly activated by cyclic adenosine monophosphate/phosphoinositide 3-kinase/protein kinase B (Epac/PI3K/Akt), cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), and adenosine monophosphate-activated protein kinase/sirtuin 1 (AMPK/SIRT1) pathways, which enhance mitochondrial function, autophagy, and metabolic reprogramming

Similarly, in the A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes (SOUL) study, which randomized patients with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both to oral semaglutide versus placebo, the primary outcome of major adverse cardiovascular event occurred in 12.0% of the patients receiving semaglutide and 13.8% of the patients receiving placebo (hazard ratio, 0.86