Sodium-Glucose Cotransporter-2 Inhibitors, Glucagon-like Peptide-1 Receptor Agonists, and Frailty Progression in Older Adults with Type 2 Diabetes

<p dir="ltr">Objective: Older adults with type 2 diabetes are at high risk for frailty. The effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on frailty remain uncertain.</p><p dir="ltr">Research Design and Methods: Using a 7% random sample of Medicare data, we compared new users of dipeptidyl peptidase-4 inhibitors (DPP-4i), GLP-1RA, SGLT-2i, and sulfonylurea on one-year frailty progression, measured by a claims-based frailty index (CFI) (range: 0 to 1; higher scores indicate greater frailty). Mediation analyses assessed whether cardiovascular or safety events explained differences in frailty progression.</p><p dir="ltr">Results: Compared to DPP-4i users, mean CFI change (95% CI) was significantly lower for GLP-1RA (-0.007 [-0.011 to -0.004]) and SGLT-2i users (-0.005 [-0.008 to -0.002]); sulfonylurea users showed no difference. These associations were minimally mediated by cardiovascular or safety events.</p><p dir="ltr">Conclusions: GLP-1RA and SGLT-2i may slow frailty progression through mechanisms independent of cardiovascular benefits. Future trials should confirm these preliminary findings.</p>