Abstract

Background: There is increased use of dual glucagon like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitor (SGLT2i) therapy, but real-world evidence on the renal benefit is lacking. Aim: To compare the dual use of GLP-1 RA and SGLT2i to other dual second-line type 2 diabetes therapies with respect to renal outcomes. Methods: From 2010-2021 patients from the Danish nationwide registries were followed from start of dual second-line type 2 diabetes treatment. Outcomes were chronic renal disease, end-stage renal disease and >50% eGFR decrease from baseline. The estimated risk following 1 of 4 dual therapy combinations was determined using a longitudinal causal inference framework assuming all patients followed one dual therapy for 5 years. Results: In total 87,201 persons were included (GLP-1 RA and SGLT2i: 14,831, GLP-1 RA and DPP4/SU/TZD: 20,417, SGLT2i and DPP4/SU/TZD: 22,803, dual DPP4/SU/TZD: 29,150). The 5-year risk ratio (95%CI) of dual GLP-1 RA and SGLT2i therapy compared to reference (dual DPP4/SU/TZD) for chronic renal disease: 1.03 (0.97;1.08), end-stage renal disease: 0.12 (0.09;0.15) and >50% decrease in eGFR: 0.52 (0.45;0.59). Conclusion: Dual therapy with GLP-1 RA and SGLT2i compared to other dual therapies results in greater risk reduction of end-stage renal disease and eGFR decline, while dual SGLT2i and DPP4/SU/TZD showed greater risk reduction of chronic renal disease. Disclosure B. Zareini: None. T. A. Gerds: None. K. K. Sørensen: None. K. K. Clemmensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. K. Kvist: Employee; Novo Nordisk A/S. J. David: Employee; Novo Nordisk A/S, Sanofi. C. Torp-pedersen: Research Support; Novo Nordisk, Bayer Inc.

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