Diabetes CareType 2 DiabetesCohortJanuary 1, 2026

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

Park CM, Thanapluetiwong S, Chen X, Oh G, Ko D, Kim DH

Key Finding

In older adults with type 2 diabetes, GLP-1 receptor agonists and SGLT-2 inhibitors slowed frailty progression by 0.007 and 0.005 points respectively on a 0-1 frailty scale compared to DPP-4 inhibitors over one year.

What This Study Found

Think of frailty like a car slowly breaking down - everything from the engine to the brakes starts working less efficiently. Scientists used Medicare data to track 'frailty scores' (like a report card from 0 to 1, where higher numbers mean more broken down) in older diabetic adults taking different medications. They found that people taking GLP-1 drugs (like Ozempic) and SGLT-2 inhibitors (like Jardiance) had their 'frailty car' break down more slowly compared to those taking DPP-4 inhibitors (like Januvia). The protective effect was small but consistent - about 0.007 points less frailty progression for GLP-1s and 0.005 points for SGLT-2s. Interestingly, this wasn't because these drugs prevented heart attacks or other major events - it seems they're protecting against frailty through some other mechanism, like a mechanic who keeps your car running smoother in ways you can't immediately see.

Statistics Decoded

The confidence intervals (-0.011 to -0.004 for GLP-1s and -0.008 to -0.002 for SGLT-2s) tell us we can be pretty confident the real benefit falls somewhere in these ranges - it's not just random chance. The fact that sulfonylureas showed 'no difference' means they performed about the same as DPP-4 inhibitors. The 7% Medicare sample represents a massive real-world study of actual patients, not a controlled trial. The frailty index scale from 0-1 means even small changes like 0.007 could be meaningful when you're talking about maintaining independence in daily life.

Why This Matters

This suggests GLP-1 and SGLT-2 drugs might help older diabetic adults stay stronger and more independent longer, beyond just controlling blood sugar or preventing heart problems. For doctors choosing diabetes medications in older patients, this adds another reason to consider these newer drugs over older options like DPP-4 inhibitors.

Original Abstract

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. 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. 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. GLP-1RAs and SGLT-2is may slow frailty progression through mechanisms independent of cardiovascular benefits. Future trials should confirm these preliminary findings.