Effect of sodium-glucose cotransporter-2 inhibitors on kidney outcomes of individuals with type 2 diabetes according to blood pressure levels

AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have proved kidney-protective. Given that the SGLT2 inhibitors lower blood pressure (BP), the magnitude of their kidney benefits may vary depending on an individual's BP. Therefore, we investigated whether baseline BP modifies the effect of SGLT2 inhibitors on kidney function. METHODS AND RESULTS: This study included individuals with SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors newly prescribed for type 2 diabetes using a nationwide epidemiological cohort and performed propensity score matching (1:2). The primary outcome was the annual estimated glomerular filtration rate (eGFR) decline. We further investigated the interaction effect of systolic BP (SBP) at the time of prescription using a 3-knot restricted cubic spline model. We analysed 2148 individuals with SGLT2 inhibitor prescriptions and 4296 matched individuals with DPP4 inhibitor prescriptions. Overall, the annual eGFR decline was less pronounced in the SGLT2 inhibitor group than in the DPP4 inhibitor group (-1.32 mL/min/1.73 m2 vs. -1.50 mL/min/1.73 m2). The treatment effect of SGLT2 inhibitors over DPP4 inhibitors was augmented with higher SBP (P for interaction = 0.0199). Further, after adjusting the definition of outcomes to a 30 or 40% reduction in eGFR, the advantages of SGLT2 inhibitors persisted, with a trend of augmented effect with higher SBP. Notably, annual eGFR decline was exacerbated for females presented with lower SBP when treated with SGLT2 inhibitors compared with DPP4 inhibitors. CONCLUSION: This nationwide cohort analysis demonstrated that the kidney-protective effect of SGLT2 inhibitors could be modified by baseline SBP, highlighting the importance of patient selection by assessing their BP.