Effect of combined sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonist therapy in patients with chronic kidney disease: a real-world analysis.

Abstract

Background This study aimed to evaluate the kidney, cardiovascular, and mortality outcomes of combined sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy compared with SGLT2i monotherapy in patients with chronic kidney disease (CKD). Methods Using TriNetX electronic health records, we compared patients initiating combined therapy with those initiating SGLT2i alone. Propensity score matching (1:1) was applied. The index date was defined as treatment initiation, with patients required to maintain the assigned treatment strategy during the first 6 months. Outcome follow-up began 6 months after the index date and continued to 2 years after the index date. Primary outcomes were major adverse kidney events (MAKE) and major adverse cardiovascular events (MACE), and the secondary outcome was all-cause mortality. Results Among 178,930 patients, 1,154 (0.65%) initiated combined therapy of SGLT2i and GLP-1RA, and 24,134 (13.49%) initiated monotherapy of SGLT2i. After matching, each group included 1,150 patients. Combined therapy was associated with a lower risk of MAKE (adjusted hazard ratio [aHR], 0.62; 95% confidence interval [CI], 0.48-0.80; p < 0.01) and all-cause mortality (aHR, 0.58; 95% CI, 0.40-0.83; p < 0.01) compared with SGLT2i alone. There was no significant reduction in risk of MACE (aHR, 0.88; 95% CI, 0.70-1.11; p = 0.29). Conclusion Among patients with CKD, initiation of combined SGLT2i and GLP-1RA therapy was associated with lower risks of MAKE and all-cause mortality compared with SGLT2i monotherapy. Further studies are needed to clarify effects on kidney and mortality outcomes.