Cardiovascular and renal protection of SGLT2i in early-stage type 2 diabetes: the DIAB-CV-AP study.

BACKGROUND AND AIM: SGLT2i showed in clinical trials renal and cardiovascular (CV) benefit. To analyse the prevention effect of SGLT2i on CV and renal events in primary care patients with type 2 diabetes mellitus (T2DM) requiring intensification beyond metformin monotherapy. METHODS AND RESULTS: Retrospective cohort study using BIFAP, the primary care database of the Spanish National Health System. Patients with T2DM receiving metformin who initiated a second non-insulin antidiabetic drug (NIAD) between January 2014 and December 2019 were classified as SGLT2i users or other NIAD users. CV events included myocardial infarction, stroke, peripheral arterial disease, and heart failure. Renal events were defined as deterioration of eGFR ≥40%, increase in ACR ≥30%, end-stage renal disease (eGFR <15 mL/min), or renal death. Propensity score matching was applied to minimize confounding by indication. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals. E-values were calculated to assess robustness to unmeasured confounding. After matching, 11,746 patients were analyzed (5873 per group). SGLT2i was associated with a lower risk of renal events (HR 0.303 [0.227-0.403], p < 0.001; E-value 6.06, lower CI bound 4.40), CV events (HR 0.702 [0.627-0.814], p < 0.001; E-value 2.20, lower CI bound 1.76), and all-cause mortality (HR 0.285 [0.224-0.363], p < 0.001; E-value 6.48, lower CI bound 4.95). No increase in adverse events was observed. CONCLUSIONS: In primary care patients with early-stage T2DM requiring intensification beyond metformin, SGLT2i was associated with substantial reductions in cardiovascular events, renal progression, and all-cause mortality, with robust E-values supporting these findings against unmeasured confounding.