Effect of Sodium-Glucose Cotransporter-2 Inhibitors on Frailty in Patients with Heart Failure

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2is) induce body weight and muscle loss due to the excretion of glucose in the urine, which may worsen frailty in patients with heart failure (HF). However, the impact of SGLT2is on frailty-related events in patients with HF has not been fully elucidated. Methods In this analysis of global electronic health records, patients with HF and type 2 diabetes mellitus (T2DM) who received SGLT2is were compared to those who received sitagliptin treatment from 2016 to 2021. A composite endpoint of death or new incidence of frailty-related events, including 1) mobility impairments, 2) falls and fractures, 3) pressure ulcers and weight loss, 4) incontinence, 5) dependency and caregiving, 6) dementia and delirium, and 7) anxiety and depression, was analyzed using propensity score (PS) matching. Results After PS matching, 8,148 of the 16,989 patients in the SGLT2i group were matched to 8,148 of the 18,278 patients in the sitagliptin group. The incidence of the composite endpoint and its components was lower in the SGLT2i group than in the sitagliptin group [composite endpoint, 68.1% vs. 72.6%, hazard ratio (HR) 0.85 (0.82-0.89), p <0.001; mortality, 20.4% vs. 28.2%, HR 0.69 (0.65-0.74), p <0.001; frailty-related events, 63.2% vs. 66.6%, HR 0.87 (0.84-0.91), p <0.001]. All components of frailty-related events were observed less frequently in the SGLT2i group. Conclusions SGLT2is correlated with a lower incidence of death and frailty-related events than sitagliptin in patients with HF and T2DM.