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

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.