In a 241,981-patient emulated trial using modern causal methods, sustained GLP‑1RA use yielded the lowest 2.5‑year MACE risk, followed by SGLT2is, sulfonylureas, and DPP4is; the GLP‑1RA advantage over SGLT2is was greatest in older adults and those with ASCVD, HF, or kidney impairment.