Liraglutide Might Have Synergistic Renal Protection Effect with SGLT2 Inhibitors in Rapidly Progressive Diabetic Kidney Disease

Objective: SGLT2 inhibitor (SGLT2i) and GLP-1 receptor agonist (GLP-1RA) should be considered for patients with type 2 diabetes (T2D) with CKD. But very few data are available whether synergistic effects of both drugs exist. We assessed annual eGFR decline rate by adding SGLT2i in patients with T2D on GLP-1RA therapy. Methods: A total of 75 patients with T2D with CKD stage 3-4, treated by SGLT2i (empagliflozin 65%) 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. Macroalbuminuria existed in 49% (37/75). Average age was 70.3±12.2 yrs old. GLP-1RA (Liraglutide: n=36) was initially or additionally used in 41%, 64% and 44% respectively for glucose management, considering for ASCVD. Individual eGFR decline rate (slope) was calculated from the data for 46±20 months before using SGLT2i and 31±9 months after adding it. The effects on slopes by SGLT-2i, GLP-1RA combination therapies (GLP-1RA initiated at different timing) were compared with those without GLP-1RA therapy. Results: 1) i) Baseline on GLP-1RA initiation therapy -5.2±5.3 improved to -2.2±1.4 (P<0.05) after SGLT2i added. (n=11) ii) Slopes -5.0±3.5 improved to -1.2±4.5 (P<0.03) with simultaneous intensification by SGLT2i + GLP-1RA. (n=13) iii) Slopes -14.6±18.0 improved to -5.4±5.5 (P<0.05) by intensification by GLP-RA, then improved to -2.6±3.3 (P<0.05) with SGLT2i added. (n=14) In this rapidly declining group, macroalbuminuria highly existed in 71% (10/14), and nephrosis existed in 36% (5/14), but nephrosis all came into remission through this therapy. 2) SGLT2i monotherapy (n=37): Slopes -4.1±3.0 improved to -1.2±3.1 ml/min/1.73m2/year (P<0.001) after SGLT2i added. On this background, macroalbuminuria less existed (46%), and nephrosis existed none. Conclusion: Liraglutide might have synergistic renal protection effects with SGLT2i in rapidly progressive DKD. Disclosure K. Kashima: None. H. Shimizu: None. M. Yamada: None.