In a propensity-score-matched cohort of 36,150 adults with moderate-to-severe CKD (eGFR 15–60 mL/min/1.73 m²), initiating an SGLT2 inhibitor was associated with a 24% lower hazard of a composite endpoint—all-cause death, new-onset heart failure, hemodialysis, or eGFR decline below 15 mL/min/1.73 m²—compared with initiating an ACE inhibitor or ARB (15.6% vs. 19.9%; HR 0.76, 95% CI 0.72–0.80). Benefits held across diabetes status, CKD severity, albuminuria level, and drug subtype.
This finding carries meaningful clinical weight. Until recently, RAS inhibitors were the unchallenged cornerstone of CKD management, and SGLT2 inhibitors were studied primarily as add-on therapy atop existing RASi. This study reframes the question: when initiating pharmacotherapy de novo, SGLT2 inhibitors may be the stronger first choice. The effect size is not trivial—a 4.3 percentage-point absolute risk reduction over two years translates to roughly one event prevented for every 23 patients treated.
Caveats matter, however. This is a retrospective observational study; despite careful propensity-score matching, residual confounding from unmeasured variables (physician preference, dietary habits, adherence) cannot be excluded. The database spans only 2020–2023, limiting follow-up. Clinicians should also note that current guidelines still recommend RASi for proteinuric CKD, and the two drug classes may complement rather than replace each other. Nonetheless, the scale—over 18,000 matched pairs—and consistency across subgroups make this a clinically significant, practice-shaping signal worth discussing with prescribers.