Abstract

While the kidney protective effects of sodium glucose co-transporter-2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes. Using a nationwide claims database, we studied 6354 older adults (≥ 60 years of age) who had diabetes and newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decline in the rate of estimated glomerular filtration rate (eGFR), which was obtained using a linear mixed-effects model with an unstructured covariance. Following propensity score matching, 6354 individuals including 1271 SGLT2 inhibitor users and 5083 DPP4 inhibitor users (median age: 68 [65-70] years); men, 60.4%; median eGFR:69.0 [59.1-79.0] ml/min/1.73 m2, median hemoglobin A1c [HbA1c]:6.9 [6.5-7.4]%) were analyzed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users (-0.97 [95% CI, -1.24 to -0.70] ml/min/1.73m2 vs. -1.83 [95% CI, -1.97 to -1.69] ml/min/1.73m2 per year; p for interaction<0.001). This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin-angiotensin system inhibitor use, and baseline eGFR. Additionally, the risk of a≥20%, ≥ 30%, and≥40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than that in DPP4 inhibitor users. Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decline in eGFR was slower in individuals aged≥60 years with diabetes who were prescribed SGLT2 inhibitors compared to those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes.

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