Kidney Effectiveness and Safety of Adding Spironolactone in Patients With Type 2 Diabetes Receiving Renin–Angiotensin System Inhibitors Therapy

We evaluated the renal outcomes and safety of spironolactone added to renin-angiotensin system inhibitors (RASis) among patients with type 2 diabetes (T2D), given its uncertain role alongside RASis, the cornerstone of T2D with renal disease management. In this retrospective study at National Cheng Kung University Hospital (2014-2021), we identified adult T2D patients receiving RASis alone or combined with spironolactone. Propensity score matching between treatment groups was implemented to achieve between-group comparability. The primary outcome was a composite renal outcome (including end-stage renal disease [ESRD], renal transplant, or a ≥ 30% estimated glomerular filtration rate [eGFR] decline). Secondary outcomes included proteinuria, major adverse cardiovascular events, and hyperkalemia. Cox proportional hazard model analyses were adopted to assess the treatment outcomes. 404 PS-matched pairs of RASis-alone and RASis+spironolactone users were included. Adding spironolactone to RASis was associated with increased composite renal event (hazard ratio [95% CI]: 1.27 [1.06-1.51]), persistent eGFR decline ≥ 30% (1.31 [1.09-1.58]), and hyperkalemia (1.57 [1.21-2.04]) risks while associated with a higher likelihood of achieving ≥ 30% proteinuria reduction (HR 1.34 [1.12-1.60]). Having heart failure (HF) was a significant effect modifier, that is, using RASis+spironolactone versus RASis alone was associated with a lower ESRD/renal transplant risk among patients with HF (0.62 [0.38-1.02]) but an increased risk for those without HF (1.32 [0.98-1.78]) (p for interaction = 0.011). Adding spironolactone to RASis might increase renal adverse events and hyperkalemia but reduce proteinuria in T2D patients. Notably, heart failure status significantly modified these associations, underscoring the importance of personalized medicine.