Kidney Failure Risk Modifies Comparative Effectiveness of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Cardiovascular-Kidney-Metabolic (CKM) Events

Le résumé fourni par la source

Background: A better understanding of heterogeneity within CKM syndrome is a research priority. Whether kidney failure risk modifies the comparative effectiveness of SGLT2i vs. GLP-1RA is clinically important. Methods: We conducted an active comparator, new user study of SGLT2i, GLP-1RA and insulin glargine (IG) in a national cohort of veterans with T2D on metformin who started a study drug 2018-2021 (N=160,428). 5-year kidney failure risk equation (KFRE) score was calculated using age, sex, eGFR and UACR. Follow-up was through 3/31/23. Kidney failure (Stage V CKD by follow-up eGFR or ESKD by ICD codes and USRDS linkage), MACE (HF, MI or stroke ICD codes), CKM composite (kidney failure or MACE) and all-cause death were outcomes. We related SGLT2i vs GLP-1RA initiation with subsequent outcomes in separate inverse probably weighted Cox regression models within each KFRE subgroup (<2%, 2-<6%, ≥6%, and missing). We compared regression coefficients of SGLT2i vs. GLP-1RA in KFRE 2-<6% vs. ≥6% with Wald tests to examine effect modification. Results: IG (N=54,015) had higher risk compared to either SGLT2i (N=84,625) or GLP-1RA (N=21,788) consistently. Compared to GLP-1RA, SGLT2i had significantly higher hazard of kidney failure, MACE and CKM composite and equivalent hazard of death in KFRE 2-<6% group. In KFRE ≥6%, SGLT2i had non-significantly lower hazard of kidney failure, MACE, CKM composite and death (Figure). There was significant effect modification of SGLT2i vs. GLP-1RA comparisons by KFRE risk groups 2-<6% vs. ≥6% for kidney failure (p=0.002), MACE (p=0.004), and CKM composite (p=0.006). Conclusion: We present novel evidence that KFRE scores modify the real-world comparative effectiveness of SGLT2i vs. GLP-1RA on kidney failure and CKM outcomes in T2D, favoring GLP-1RA in KFRE 2-<6% and SGLT2i in KFRE ≥6%. Funding: NIDDK Support - NIDDK Support, NIDDK Support, Veterans Affairs Support

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.