IRS1 and Alzheimer disease: Promising results from early clinical trials in MCI and mild AD of insulin sensitizers (metformin, [82]), GLP-1 receptor agonist/ incretin analogs (liraglutide, [83]), intranasal (IN) insulin [84, 85] and insulin- sensitizing PPAR-γ agonists that target genes such as IRS-1, GLUT-4 and PI3K [86, 87] (Rosiglitazone, [88]; Pioglitazone, [89]), support finding druggable targets in this pathway and several relevant ongoing trials: Metformin (phase 3, NCT04098666), liraglutide (phase2b, NCT 01843075, [90]) and semaglutide (phase 3, NCT 04777396).