GLP-1 receptor agonist use during immune checkpoint inhibitor therapy is associated with mortality and Immune-Related adverse events across cancer types in People with type 2 Diabetes: A Target-Trial emulation.

AIMS: To evaluate whether Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use at immune checkpoint inhibitor (ICI) start is associated with mortality, healthcare use, and immune-related adverse events in adults with type 2 diabetes (T2D). METHODS: A target-trial emulation was conducted in the TriNetX US Collaborative Network among adults with cancer and T2D starting an ICI, with or without overlapping GLP-1 RA at ICI start. A new-user 1:1 propensity-score-matched, intention-to-treat design yielded 2,903 per group and 36-month follow-up. Primary endpoint was all-cause mortality; key secondaries were hospitalization, and composite immune-related adverse events (irAEs). Prespecified per-protocol, 90-day landmark, and semaglutide-only analyses assessed robustness. RESULTS: GLP-1 RA co-exposure was associated with lower mortality (hazard ratio [HR] 0.55, 95 % CI 0.51-0.61; 36-month absolute risk difference [ARD] - 16.41 %; number needed to treat [NNT] 5). Hospitalization (HR 0.76; ARD - 7.06 %; NNT 11), and composite irAEs (43.93 % vs 51.51 %; ARD - 7.58 %; NNT 11) were also lower. Diabetic-retinopathy progression (HR 1.75; ARD + 2.71 %) and non-arteritic anterior ischemic optic neuropathy (HR 1.51) were higher; hypoglycaemia, acute kidney injury, and dehydration/orthostatic hypotension were lower. CONCLUSIONS: GLP-1 RA use during ICI therapy correlated with lower mortality, reduced acute care, fewer irAEs; ophthalmic signals warrant monitoring.