MON-299 KIDNEY OUTCOMES ASSOCIATED WITH INITIATION OF SODIUM GLUCOSE CO-TRANSPORTER 2 INHIBITION VERSUS OTHER GLUCOSE LOWERING DRUGS - AN ANALYSIS FROM THE CVD-REAL STUDY

Abstract

Recent cardiovascular outcome trials have shown that sodium glucose co-transporter 2 inhibitors (SGLT-2i) slow progression of chronic kidney disease in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to patients with type 2 diabetes treated in clinical practice is unknown. The purpose of this study was to determine kidney outcomes and estimated glomerular filtration rate (eGFR) decline in patients initiating SGLT-2i versus other glucose lowering drugs (oGLDs) in a real world setting. New users of SGLT-2i and oGLDs were identified via claims, medical records, and national registries in Japan and Israel. Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching. Propensity score included amongst others baseline eGFR and eGFR slope prior to SGLT-2i or oGLDs initiation (index date). After propensity score matching more than 25000 individuals were included. The primary outcome measure was the total eGFR slope after the index date calculated with a linear mixed regression model. Differences in eGFR slope between SGLT-2is and oGLDs were calculated by country and pooled using weighted meta-analyses. Additional outcomes were a composite endpoint of 50% eGFR decline or end-stage kidney disease (ESKD) and their individual components. Hazard ratios (HRs) for these outcomes, calculated with Cox proportional hazard models, were assessed by country and pooled using weighted meta-analysis. After propensity matching, there were 14120 episodes of treatment initiation in each group. Dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin accounted for 30.1%, 62.8%, 1.6%, 3.3%, 0.9%, and 1.3% of SGLT2i initiation, respectively. At the index date, mean age was 61.5 years, eGFR was 91.5 ml/min/1.73m2, HbA1c was 8.4%, and 40.4% were female. Annual eGFR change prior to oGLDs or SGLT2i initiation was −0.75 and −0.71 ml/min/1.73m2/year, respectively. The annual rate of eGFR change during oGLDs was −1.0 (95%CI −1.1 to −0.9) ml/min/1.73m2/year and during SGLT2i treatment 0.0 ml/min/1.73m2/year (95%CI −0.1 to 0.1; p vs. oGLDs <0.001). During a mean follow-up of 18 months, 52 (0.37%) patients reached the primary renal endpoint in the SGLT2i group and 104 (0.74%) in the oGLDs group (hazard ratio 0.51 [95%CI 0.36 to 0.71]). Use of SGLT2i versus oGLD was associated with a lower risk of the individual components of the endpoint: ESKD (HR 0.32 [95%CI 0.15 to 0.71); 50% eGFR decline (HR 0.53 [95%CI 0.38 to 0.76]). These effects were consistent across countries. In this large international real world clinical practice database of patients with type 2 diabetes, SGLT2i use was associated with a slower rate of renal function decline and lower risk of clinically meaningful renal events compared to oGLDs. These data indicate that the beneficial effects of SGLT2i on kidney function as observed in clinical trials translate to daily clinical practice.