Although ischemic colitis is more typically linked to vascular disease, hypotension, or vasoconstrictive drugs, recent reports have suggested an association with glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide and tirzepatide. The temporal relationship with tirzepatide initiation, absence of infection, and confirmatory histology strongly support drug-induced ischemia in this case, underscoring the importance of clinician awareness of this rare but significant complication in patients presenting with rectal bleeding or abdominal pain while on incretin-based therapy. The gene discussed is GLP1R; the disease is ischemia.