Individualized Estimated GFR Slope Analysis Is Needed to Preserve Renal Function by SGLT2 Inhibitors in Patients with DKD

Objective: SGLT2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) with CKD. Since eGFR declining speed is different in each patient, we assessed renal protective effects by individual eGFR slope analysis. Methods: A total of 75 patients with T2D with advanced CKD stage 3-4, treated by SGLT2i (empagliflozin 65% and others) were analyzed. The duration of diabetes at the time of recruitment were as follows: stage 3a (n=29); 11.9±5.4 yrs, stage 3b (n=28); 19.9±12.1 yrs, and stage 4 (n=18); 13.8±8.5 yrs. The mean of age was 70.3±12.2 yrs old. GLP-1RA (Liraglutide; n=36, Duraglutide; n=1) was used in 41%, 64% and 44% respectively. Most rapid baseline slopes were calculated from 46±20 months before using SGLT2i, and slopes after adding SGLT2i were calculated from 31±9 months. Results: 1) In total, the initiation of SGLT2i decreased eGFR from 46.1±14.1 to 43.6±13.5ml/min/1.73m2 (P<0.001) on first month. 2) Individualized most rapid slopes were improved from -6.4±9.1 to -1.6±3.3ml/min/1.73m2/year (P<0.001). 3) Slopes were improved in all stages, stage 3a: -4.1±3.7 to -1.1±3.4 (P<0.001) and stage 3b; -4.9±3.7 to -1.6±2.9 (P<0.001), and stage 4; -12.4±16.3 to -2.2±3.7ml/min/1.73m2/year (P<0.03). 3) The proportion of responders (defined as their ratios of slopes are reduced < 1.0 after addition of SGLT2i) in each stage were as follows: stage 3a; (22/29), stage 3b; (22/28), stage 4; (16/18). Slopes in responders (61/75) were improved as follows, -7.4±9.8 to -1.0±2.9ml/min/1.73m2/year (P<0.0001). Slopes in non-responders (14/75) were worsened as follows, -2.0±2.0 to -4.1±3.5ml/min/1.73m2/year (P<0.001). 4) Slopes in rapid decliners (13/75) were remarkably improved from -18.9±16.4 to -1.5±3.6ml/min/1.73m2/year (P<0.01) with combined use of GLP-1RA (11/13), who had macro-albuminuria (9/13) and nephrosis (7/13). Conclusion: To pursuit the renal benefits of SGLT2i, individualized slope analysis is needed for patient-centered care. Disclosure K. Kashima: None. H. Shimizu: None. M. Yamada: None.