GLP-1 Continuation Cuts Cardiovascular Events Over Three Years but Early Discontinuation Reverses Gains

The BMJ Medicine analysis tracked 132,551 GLP-1 initiators against 201,136 sulfonylurea users, documenting time-dependent risk reduction that strengthened with persistence. Discontinuation clustered in year one and coincided with rapid loss of the accrued cardiovascular benefit, consistent with the drug class acting through sustained anti-inflammatory and endothelial effects rather than transient weight loss alone. Parallel JAHA-reported data on tirzepatide showed a 30% lower composite of stroke and heart failure hospitalization after TAVR and a 62% mortality reduction post-PCI versus dulaglutide, extending signals beyond semaglutide. These patterns align with the SELECT RCT findings yet remain vulnerable to channeling bias because the studies are observational and several key datasets have not completed peer review. Residual questions include whether the same trajectory holds in non-diabetic obesity populations and how quickly risk rebounds after planned drug holidays. Next required evidence is a pragmatic randomized withdrawal trial measuring hard endpoints at 12 and 24 months post-discontinuation.