Impact of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Kidney Failure Risk Prediction

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Background: The Kidney Failure Risk Equation (KFRE) is KDIGO-recommended for risk prediction to guide patient care. Whether the use of SGLT2i or GLP-1RA modify KFRE risk prediction is clinically relevant. Methods: We performed an active comparator, new user study in a national cohort of veterans with T2D on metformin without ESKD who initiated SGLT2i, non-exendin GLP-1RA or insulin glargine (IG) from 1/1/18-12/31/21 (N=160,428). Inverse probability weighting minimized measured confounding. Age, sex, eGFR and UACR were used to calculate 5-year KFRE and define subgroups <2%, 2-<6%, ≥6%. Follow-up was until 3/31/23 for kidney failure (eGFR <15 over 2 consecutive labs, dialysis dependence or transplant by diagnostic code or USRDS linkage) and death. We examined whether study drug class modified the KFRE’s relationship to three-year cumulative incidence of kidney failure under competing risk framework. Results: In KFRE ≥6%, kidney failure and death before kidney failure were the highest in IG, followed by GLP-1RA then SGLT2i. In KFRE 2-<6%, kidney failure incidence was highest in SGLT2i new-users, likely due to a large competing risk of death, followed by IG then GLP-1RA (Table). Visually, SGLT2i reduced kidney failure rates especially in KFRE≥6%, while GLP-1RA appeared most protective in KFRE 2-<6% (Figure). Conclusion: SGLT2i and GLP-1RA reduced expected kidney failure incidence compared to IG users of comparable KFRE score. Kidney failure risk prediction equations need to updated with terms for SGLT2i or GLP-1RA use. Funding: NIDDK Support - NIDDK Support, NIDDK Support, Veterans Affairs Support - KFRE Subgroup Incidence in SGLT2i new-users (N=48,988) Incidence in GLP-1RA new-users (N=12,379) Incidence in Insulin Glargine new-users (N=28,472) 3-year Incidence of Kidney Failure with Competing Risk of Death <2% 0.55% 0.59% 0.72% 2 - <6% 4.58% 1.73% 3.51% ≥6% 7.93% 12.06% 15.14% 3-year incidence of All-Cause Death before Kidney Failure <2% 6.85% 6.27% 10.13% 2 - <6% 13.88% 16.24% 17.36% ≥6% 14.38% 21.58% 20.71%

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