Keywords: Frailty , SGLT2 inhibitors, GLP-1 receptor agonists, Type 2 Diabetes

Background:

SGLT2 inhibitors and GLP-1 receptor agonists improve glycemic control and provide cardiovascular and renal benefits, including in frail older adults. Frailty affects a substantial proportion of older adults with type 2 diabetes (T2D), a condition that accelerates biological aging and predisposes to frailty through multiple pathophysiologic mechanisms. Emerging preclinical and observational evidence suggests that SGLT2is and GLP-1RAs may attenuate frailty progression via anti-inflammatory and anti-senescent pathways, beyond cardiovascular risk reduction.

Research questions:

What is the effect of SGLT2is and GLP-1RAs treatment on long-term frailty progression?

Method:

A retrospective cohort study using electronic medical records from Clalit Health Services, Israel’s largest health care organization. Adults aged ≥65 years with T2D who newly initiated SGLT2is or GLP-1RAs were compared with new users of DPP-4 inhibitors between 2015 and 2025. Using a propensity score–matched, active-comparator, new-user design, frailty progression was assessed longitudinally using electronic frailty index scores. Patients were followed from drug initiation until treatment discontinuation, treatment switch, death, loss of coverage, or study end. Potential mediators, including cardiovascular events, diabetes-related complications, glycemic control, kidney function, and weight change, were evaluated. Frailty was defined using a validated 28-item electronic frailty index based on the cumulative deficit model, classifying patients as non-frail or mildly, moderately, or severely frail.

Results:

No results yet

Conclusions:

No conclusions yet

Points for discussion:

The effect of SGLT2is and GLP-1RAs treatment on frailty progression

SGLT2is treatment in frail older adults.

GLP-1RAs treatment in frail older adults.