878-P: Maximize Benefits of SGLT2 Inhibitors in People with Advanced CKD Stages with Type 2 Diabetes

Objective: SGLT2 inhibitor (SGLT2i) should be considered for people with CKD with type 2 diabetes (T2D) . Since eGFR declining speed and responsiveness to SGLT2i are different in each person, 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, stage 3b (n=28) ; 19.9±12.1, and stage 4 (n=18) ; 13.8±8.5 years. The mean of age was 70.3±12.2 year-old. GLP-1RAs was used in 41%, 64% and 44% respectively. Most rapid baseline eGFR slopes were calculated from 45.7±19.9 months before using SGLT2i, and slopes after adding SGLT2i were calculated from 39.2±11.4 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 the first month. 2) In total, averaged individualized eGFR slopes were improved from -6.4±9.1 to -1.5±3.2ml/min/1.73m²/year (P<0.001) . The rate of responders (responder: defined as slope are attenuated vs. baseline) in each stage were as follows: stage 3a; (22/29) , stage 3b; (22/28) , stage 4; (16/18) . Slopes in responders (60/75) were improved as follows, -7.5±9.8 to -0.8±3.0 ml/min/1.73m²/year (P<0.001) . Slopes in non-responders (15/75) were worsened as follows, -2.0±2.0 to -4.0±3.2ml/min/1.73m²/year (P<0.001) . Although no clear background differences could be found, responders were more rapid eGFR decliners and highly had macro-albuminuria (53% vs. 33%) . 3) Slopes were improved in all stages, stage 3a: -4.1±3.7 to -1.2±3.2 (P<0.001) and stage 3b; -4.9±3.7 to -1.3±3.1 (P<0.001) , and stage 4; -12.4±16.3 to -2.0±3.6ml/min/1.73m²/year (P<0.01) . In stage 4, nephrosis highly existed in 28% at the baseline.

Conclusion: To pursuit the renal benefits safely, especially starting SGLT2i in lower eGFR level in people with advanced CKD stages, individualized slope analysis is needed.