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Data availability The EHR database used in this study were obtained from TriNetX ( Abbreviations GLP-1RAs: Glucagon-like peptide-1 receptor agonists T2DM: Type 2 diabetes mellitus EHRs: Electronic health records SGLT2: Sodium-glucose cotransporter-2 DPP-4: Dipeptidyl peptidase-4 HR: Hazard ratios CI: Confidence intervals References Alfaris N, Waldrop S, Johnson V, Boaventura B, Kendrick K, Stanford FC (2024) GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review

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doi: 10.1038/nchembio.209

Innovative designs incorporating active comparators, adaptive frameworks, and biomarker-driven endpoints (e.g., CSF/serum NfL, p-tau, microglial PET, synaptic markers) will be critical to generate interpretable efficacy signals