From this retrospective cohort study of 140 308 US patients with type 2 diabetes treated with tirzepatide or GLP-1 RAs, we have for the first time to our knowledge presented evidence substantiating that tirzepatide therapy is associated with lower risks of all-cause mortality, MACEs, MAKEs, and AKI compared with GLP-1 RA therapy after a median follow-up of 10.5 months. Here, GLP1R is linked to rheumatoid arthritis.