Sodium–Glucose co-Transporter 2 Inhibitors in Severe Estimated Glomerular Filtration Rate Deterioration Across Cardiovascular-Kidney-Metabolic Conditions: A Pooled Analysis of Randomized Trials

AIMS: ), and whether such eGFR deterioration modified the effect of SGLT2i across CKM populations. METHODS AND RESULTS: ). Factors independently associated with a higher risk of eGFR deterioration were lower baseline eGFR and higher albuminuria, whereas allocation to SGLT2i was protective. eGFR deterioration was independently associated with a nearly twofold higher risk of subsequent cardiovascular outcomes and mortality. The beneficial impact of SGLT2i treatment on cardiovascular outcomes and mortality was maintained irrespective of patients experiencing eGFR deterioration (interaction-p >0.1 for all outcomes). Patients who experienced eGFR deterioration were more likely to permanently discontinue treatment, without significant differences in treatment discontinuation rates between the SGLT2i and placebo groups. CONCLUSIONS: Severe eGFR deterioration during follow-up was associated with an increased risk of subsequent cardiovascular events and mortality. SGLT2i reduced the probability and were beneficial irrespective of severe eGFR deterioration.