Real-world risk factors and clinical implications of early estimated glomerular filtration rate decline after sodium-glucose cotransporter-2 inhibitor therapy

Abstract

Aim

To assess the prevalence, risk factors, estimated glomerular filtration rate trajectory, and clinical implications of the early estimated glomerular filtration rate dip after sodium-glucose cotransporter 2 inhibitors in a real-world population.

Materials and Methods

We retrospectively analyzed 1,550 patients who received sodium-glucose cotransporter 2 inhibitor treatment at a single teaching hospital between 2014 and 2024. Patients were stratified into three groups based on early estimated glomerular filtration rate decline within the first 3 months of treatment: non-, moderate, and severe dippers (<10%, 10%–30%, and ≥30%, respectively).

Results

An early estimated glomerular filtration rate dip occurred in 21% of the patients; 17.6% were moderate dippers, and 3.5% were severe dippers. The risk factors for dipper classification included older age, atrial fibrillation, loop diuretic use, and high estimated glomerular filtration rate variability. Although the estimated glomerular filtration rate slopes declined progressively across dipper groups, the mean annual decline did not exceed age-expected changes even in the severe dipper group. Patients who discontinued sodium-glucose cotransporter 2 inhibitor therapy experienced a steeper decline than those who continued therapy. Three patients in the severe dipper group on concomitant loop diuretics experienced extreme estimated glomerular filtration rate reductions, which persisted during follow-up.

Conclusions

Early dips and continued sodium-glucose cotransporter 2 inhibitor use are not generally associated with unfavorable outcomes. However, caution is warranted in frail or volume-sensitive patients, particularly with concomitant diuretics.