The relationship between dietary sodium intake and cardiovascular outcomes remains complex in individuals with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). A post hoc analysis of the CREDENCE trial published in Diabetologia evaluated whether sodium intake influences cardiovascular and renal outcomes and whether treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin modifies these associations.

The analysis included 2573 participants with T2DM and CKD from the CREDENCE trial, which had a median follow-up of 2.6 years. Participants were randomized to canagliflozin 100 mg or placebo. Estimated daily sodium intake was derived from urinary measurements using a validated formula and categorized into low-normal sodium intake (LNS; n=1286) and high sodium intake (HS; n=1287) groups. Outcomes included cardiovascular death or hospitalization for heart failure, heart failure alone, a composite renal outcome, and all-cause mortality. Cox proportional hazards models were adjusted for confounders.

In the placebo group, low-normal sodium intake was associated with a higher risk of heart failure or cardiovascular death compared with high sodium intake (adjusted hazard ratio [adjHR] 1.56; 95% CI 1.10-2.23). Treatment with canagliflozin reduced this risk in the low–normal sodium group (adjHR 0.48; 95% CI 0.33-0.70) but not in the high sodium group (adjHR 1.05; 95% CI 0.73-1.53). Similar findings were observed for heart failure alone.

Sodium intake showed no association with renal outcomes, whereas canagliflozin reduced renal risk in both sodium intake groups. Neither sodium intake nor canagliflozin affected all-cause mortality. Continuous modeling showed that the risk of heart failure or cardiovascular death increased as sodium intake decreased in placebo recipients, while this gradient was attenuated among individuals receiving canagliflozin.