GLP-1 RA Should Be Used with SGLT2 Inhibitor in People with Rapidly Progressive CKD

Objective: Either GLP-1RA or SGLT2i is recommended to use in people with type 2 diabetes (T2D) with CKD. Whether these drugs jointly work for reno-protection are not well known. We evaluated add-on effects of GLP-1RA (liraglutide 95%) in Japanese people with T2D treated by SGLT2i by assessing individual eGFR trajectory. Methods: A total of 75 persons with T2D (CKD stage 3-4), treated by SGLT2i (empagliflozin 65%) were analyzed. At the time of recruitment, average age was 70.3±12.2 yr-old, the duration of diabetes was 15.4±10.1 yrs, and macroalbuminuria (Macro-Alb) existed in 49% (37/75). To trace the eGFR trajectory in each person, most rapid eGFR slope was calculated individually from the data for 46±20 months before using SGLT2i and 46±16 months after adding it. GLP-1RA was initially or additionally used in 53%. Results: 1) 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; (21/29), stage 3b; (21/28), stage 4; (16/18). Slopes in responders (58/75) were improved as follows, -7.8±9.9 to -0.8±3.0ml/min/1.73m2/year (P<0.001) with GLP-1RA use in 52%. Slopes in non-responders (17/75) were worsened as follows, -1.8±1.9 to -3.6±3.1ml/min/1.73m2/year (P<0.001), despite GLP-1RA use in 59%. Macro-Alb was observed in 53% and 35%, respectively. 2) Slopes in rapid decliners (defined as most rapid individual eGFR slope greater than -10.0ml/min/1.73m2/y) (13/75) were improved from -18.9±16.4 to -1.3±3.3ml/min/1.73m2/year (P<0.01) by combined use of GLP-1RA in 85% (11/13). Macro-Alb existed in 69% (9/13) and nephrosis in 54% (7/13). 3) Sub-analysis (one of different GLP-1RA initiation regimes): Baseline slopes -16.7±19.8 were improved to -5.0±5.8 (P<0.05) by adding GLP-1RA, then to -2.7±3.8 ml/min/1.73m2/year (vs baseline: P<0.03) by adding SGLT2i. (n=11) Macro-Alb highly existed in 82% (9/11) and nephrosis in 46% (5/11). Conclusion: GLP-1RA should be used with SGLT2i in rapid eGFR decliners or persons with Macro-Alb. Disclosure K.Kashima: None. H.Shimizu: None. M.Yamada: None.