Sitagliptin: ✔️Improved cognitive function: Significantly improved hippocampal-dependent learning, memory, and cognitive functions in the T2D-AD mouse model, as demonstrated by behavioral tests, the Novel object recognition test (NORT), and the Morris water maze (MWM). ✔️Improved brain insulin signaling via the IRS1/Akt/GSK3β pathway, thereby, reduced: Aβ accumulation by increasing insulin-degrading enzyme levels and hyperphosphorylated Tau (pTau) levels. ✔️Improved insulin sensitivity. ✔️Reduced body weight. ✔️Ameliorated inflammation and promoted the metabolic gene expression in the liver. This evidence concerns the gene IRS1 and type 2 diabetes mellitus.