Abstract
RATIONALE & OBJECTIVE: Studies of sodium-glucose cotransporter-2 (SGLT2) inhibitors assessing kidney outcomes among Asians with type 2 diabetes in a clinical setting are limited. We assessed the association of SGLT2 inhibitors with kidney and safety outcomes in a diverse multiethnic Asian population with type 2 diabetes in a clinical setting. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients with type 2 diabetes from multi-institutional SingHealth Diabetes Registry in Singapore. EXPOSURE: Initiators of SGLT2 inhibitors between 2014 to 2018 with a median follow-up duration of 25.6 months (interquartile range, 17.9-31.4). OUTCOMES: Composite kidney outcome (≥40% estimated glomerular filtration rate [eGFR] decline or incident kidney failure with replacement therapy [KFRT]), its components, rate of eGFR change, amputation, and acute kidney injury (AKI). ANALYTICAL APPROACH: Propensity scores for SGLT2 inhibitors initiation were developed, with 1:1 matching with initiators of other antidiabetic drugs. Cox proportional hazards and linear mixed effect models were employed. RESULTS: After matching, there were 4,254 patients newly initiated on either SGLT-2 inhibitors or other glucose-lowering drugs (2,127 in each group). The mean age was 63.4 (SD 9.2) years, with 48.6% women. In total, 67.8% of participants were Chinese, 11.9% Indian, 15.6% Malay, and 4.7% others. Initiating SGLT2 inhibitors was associated with lower risks of composite kidney outcome (hazard ratio [HR], 0.39; 95% CI, 0.31-0.48) and ≥40% reduction in eGFR from baseline (HR, 0.38; 95% CI, 0.31-0.48). SGLT2 inhibitor initiation was also associated with a slower eGFR decline among the intention-to-treat population (n = 1,888, difference in slope: 2.67 mL/min per 1.73 m(2) per year; 95% CI, 1.90-3.43). No significant association with amputation was found, though SGLT2 inhibitors were associated with reduced AKI risk. LIMITATIONS: Potential informed presence bias and residual and unmeasured confounding. CONCLUSIONS: SGLT2 inhibitors significantly benefit kidney outcomes in multiethnic Asians with type 2 diabetes, highlighting their role in preventing kidney complications.