Excessive Initial Renal Function Decline Following Sodium-Glucose Cotransporter-2 Inhibitor Treatment Predicts Major Adverse Cardiorenal Outcomes

Objective

To investigate how estimated glomerular filtration rate (eGFR) decline following sodium-glucose cotransporter-2 inhibitors (SGLT2i) initiation predicts long-term cardiorenal outcomes.

Methods

From 2016 to 2020, a longitudinal cohort of 4942 diabetic patients treated with SGLT2i were enrolled and followed until December 2021. Patients were categorized into mild (≤30%), moderate (>30%∼≤40%) and severe (>40%) decline groups by the maximal eGFR change between 2 to 12 weeks after SGLT2i treatment. Cox regression was used to explore the association between eGFR decline and risks of a composite outcome of all-cause mortality, major adverse cardiovascular events (MACE), and major adverse renal events (MARE) after comprehensively adjusting for clinical and laboratory confounders.

Results

After a median follow-up of 2.57 years, 125 deaths, 192 MACE, and 247 MARE occurred. Severe and moderate eGFR decline groups showed higher risks of composite outcome (severe adjusted hazard ratio [aHR], 4.56; 95% CI, 2.70 to 7.70; moderate aHR, 1.94; 95% CI, 1.17 to 3.24) and death (severe aHR, 3.54; 95% CI, 1.16 to 10.83; moderate aHR, 3.63; 95% CI, 1.22 to 10.77) vs mild decline group. The severe decline group also had higher MACE (aHR, 3.65; 95% CI, 1.76 to 7.59) and MARE (aHR, 4.94; 95% CI 2.71 to 9.01) risks, whereas the moderate decline group only demonstrated higher MARE risk (aHR, 2.25; 95% CI, 1.22 to 4.14). The results were consistent in restricted cubic spline and sensitivity analyses.

Conclusion

An excessive eGFR decline greater than 30% after SGLT2i initiation was progressively associated with higher hazards of major adverse cardiorenal events. Careful and vigilant surveillance with timely treatment in such patients are suggested.