Park C.M.Thanapluetiwong S.Chen X.Oh G.Ko D.Kim D.H.Mahidol University2026-02-062026-02-062026-01-01Diabetes Care Vol.49 No.1 (2026) , 147-15101495992https://repository.li.mahidol.ac.th/handle/123456789/114579OBJECTIVE Older adults with type 2 diabetes are at high risk for frailty. The effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT-2is) on frailty remain uncertain. RESEARCH DESIGN AND METHODS Using a 7% random sample of Medicare data, we compared new users of dipeptidyl peptidase 4 inhibitors (DPP-4is), GLP-1RAs, SGLT-2is, and sulfonylureas on 1-year frailty progression, measured by a claims-based frailty index (CFI) (range: 0–1; higher scores indicate greater frailty). Mediation analyses assessed whether cardiovascular or safety events explained differences in frailty progression. RESULTS Compared with DPP-4i users, the mean CFI change (95% CI) was significantly lower for GLP-1RA (−0.007 [−0.011, −0.004]) and SGLT-2i (−0.005 [−0.008, −0.002]) users; no difference was found for sulfonylurea users. These associations were minimally mediated by cardiovascular or safety events. CONCLUSIONS GLP-1RAs and SGLT-2is may slow frailty progression through mechanisms independent of cardiovascular benefits. Future trials should confirm these preliminary findings.NursingMedicineArticleSCOPUS10.2337/dc25-10312-s2.0-1050254134141935554841232081