Key result
SGLT2 inhibitors linked to ~15% fewer deaths or frailty events versus sitagliptin in HF and T2DM.
Why the study?
SGLT2 inhibitors induce weight and muscle loss which may worsen frailty in heart failure, but their impact on frailty-related events has not been fully elucidated.
Does SGLT2 inhibitor therapy reduce the composite of death or frailty-related events compared to sitagliptin in patients with heart failure and type 2 diabetes?
Cohort (n=35,267)
Yes
Does SGLT2 inhibitor therapy reduce the composite of death or frailty-related events compared to sitagliptin in patients with heart failure and type 2 diabetes?
Effect estimate: HR 0.85 (95% CI 0.82-0.89)
Absolute Event Rate: 68.1% vs 72.6%
p-value: p=<0.001
In patients with heart failure and type 2 diabetes, the initiation of SGLT2 inhibitors is associated with a significantly lower risk of mortality and new frailty-related events compared to sitagliptin.
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.
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Kitamura et al. (2025) conducted a cohort in Heart failure and type 2 diabetes mellitus (n=35,267). Sodium-glucose cotransporter-2 inhibitors (SGLT2is) vs. Sitagliptin was evaluated on Composite endpoint of death or new incidence of frailty-related events (HR 0.85, 95% CI 0.82-0.89, p=<0.001). SGLT2 inhibitors were associated with a lower incidence of death or frailty-related events compared to sitagliptin in patients with heart failure and T2DM (HR 0.85; 95% CI 0.82-0.89; p<0.001).
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