Diabetologia · 2025
Cardiovascular effectiveness and safety of SGLT2 inhibitors vs DPP4 inhibitors by dementia status: a cohort study of older adults with diabetes.
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Wu Che-Yuan, Sharma Abhinav, Edwards Jodi D, Liu Peter P, Kapral Moira K, Herrmann Nathan, Wu C Fangyun, Podolsky Sho, Swardfager Walter, Shah Baiju R
Аннотация
AIMS/HYPOTHESIS: People with dementia are at a higher risk of inappropriate medication use; however, limited data inform clinical outcomes of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in people with diabetes and comorbid dementia. We aim to investigate cardiovascular effectiveness and safety of SGLT2i vs dipeptidyl peptidase-4 inhibitors (DPP4i) in older community-dwelling adults with diabetes by dementia status.
METHODS: This population-based, target trial emulation cohort study used linkable administrative datasets of residents of Ontario, Canada. Eligible initiators of SGLT2i or DPP4i with diabetes aged ≥66 years (2016-2022) were stratified by dementia status and matched 1:1 on propensity score. The primary cardiovascular effectiveness outcome was composite of all-cause mortality or hospitalisation for ischaemic stroke, myocardial infarction or heart failure. We also investigated eight safety outcomes potentially related to SGLT2i. Incidence rate differences (IRDs) per 1000 person-years and the 95% CIs were estimated. Homogeneity in IRDs between strata was assessed using the Cochran's Q statistic. One year number needed to treat (NNT) or harm (NNH) was also estimated using the Aalen-Johansen estimator with death as a competing risk.
RESULTS: We analysed 2481 pairs with dementia and 52,196 pairs without dementia. The absolute reduction in the composite effectiveness endpoint with SGLT2i vs DPP4i initiation was greater among those with dementia (IRD [95% CI] -61.1 [-78.2, -43.9]; NNT: 20), compared to no dementia (IRD -21.7 [-23.7, -19.7]; NNT: 43; homogeneity: p<0.001). Across the individual effectiveness endpoints, SGLT2i vs DPP4i initiation in people with dementia was associated with reduced all-cause mortality (IRD -51.2 [-65.7, -36.7]; NNT: 25) and hospitalisation for heart failure (IRD -16.4 [-24.6, -8.2]; NNT: 99). For safety outcomes, SGLT2i vs DPP4i initiators with dementia showed less acute kidney injury (IRD -39.7 [-55.0, -24.4]; NNT: 76) and increased genital infection (IRD 9.7 [3.7, 15.6]; NNH: 64). The absolute increase in diabetic ketoacidosis (IRD 1.1 [0.7, 1.6] vs 5.9 [2.1, 9.8]; NNH: 785 vs 109; homogeneity: p=0.015) with SGLT2i was greater among those with dementia vs no dementia.
CONCLUSIONS/INTERPRETATION: While SGLT2i might provide cardiorenal protection among those with dementia, closer monitoring may be warranted due to greater susceptibility to diabetic ketoacidosis.
METHODS: This population-based, target trial emulation cohort study used linkable administrative datasets of residents of Ontario, Canada. Eligible initiators of SGLT2i or DPP4i with diabetes aged ≥66 years (2016-2022) were stratified by dementia status and matched 1:1 on propensity score. The primary cardiovascular effectiveness outcome was composite of all-cause mortality or hospitalisation for ischaemic stroke, myocardial infarction or heart failure. We also investigated eight safety outcomes potentially related to SGLT2i. Incidence rate differences (IRDs) per 1000 person-years and the 95% CIs were estimated. Homogeneity in IRDs between strata was assessed using the Cochran's Q statistic. One year number needed to treat (NNT) or harm (NNH) was also estimated using the Aalen-Johansen estimator with death as a competing risk.
RESULTS: We analysed 2481 pairs with dementia and 52,196 pairs without dementia. The absolute reduction in the composite effectiveness endpoint with SGLT2i vs DPP4i initiation was greater among those with dementia (IRD [95% CI] -61.1 [-78.2, -43.9]; NNT: 20), compared to no dementia (IRD -21.7 [-23.7, -19.7]; NNT: 43; homogeneity: p<0.001). Across the individual effectiveness endpoints, SGLT2i vs DPP4i initiation in people with dementia was associated with reduced all-cause mortality (IRD -51.2 [-65.7, -36.7]; NNT: 25) and hospitalisation for heart failure (IRD -16.4 [-24.6, -8.2]; NNT: 99). For safety outcomes, SGLT2i vs DPP4i initiators with dementia showed less acute kidney injury (IRD -39.7 [-55.0, -24.4]; NNT: 76) and increased genital infection (IRD 9.7 [3.7, 15.6]; NNH: 64). The absolute increase in diabetic ketoacidosis (IRD 1.1 [0.7, 1.6] vs 5.9 [2.1, 9.8]; NNH: 785 vs 109; homogeneity: p=0.015) with SGLT2i was greater among those with dementia vs no dementia.
CONCLUSIONS/INTERPRETATION: While SGLT2i might provide cardiorenal protection among those with dementia, closer monitoring may be warranted due to greater susceptibility to diabetic ketoacidosis.