chronic kidney disease, GLP-1 receptor agonists, glucose-lowering drugs, primary prevention, SGLT-2 inhibitors, type 2 diabetes, Medicine, Pharmacy and materia medica, RS1-441

Background/Objectives: The burden of chronic kidney disease (CKD) is increasing, as is the prevalence of type 2 diabetes mellitus (T2DM). Post-hoc analyses of clinical trials support that sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptors agonists (GLP-1RAs) prevent CKD in T2DM patients. Methods: We used the Spanish primary care database BIFAP to perform a retrospective cohort study with a nested case-control analysis to assess the incidence, risk factors, and the effect of glucose-lowering drugs (GLDs) on the primary prevention of CKD. Results: From a cohort of 515,701 T2DM subjects (2.75 million person-years), we found 89,075 incident CKD cases, yielding an overall incidence rate (95%CI) of 324.3 (322.1–326.5) per 10,000 person-years. In the nested case–control analysis, gout, hyperuricemia, and hyperkalemia were the factors showing the highest AORs. Long-term users (≥3 years) of GLP1-RAs and SGLT-2i, compared to other GLDs, showed a decreased risk for CKD (AOR = 0.85; 95%CI: 0.73–0.99 and AOR = 0.89; 95%CI: 0.74–1.08, respectively), and for incident CKD at KDIGO stages G3-G5 (AOR = 0.72; 95%CI: 0.56–0.94 and AOR = 0.64; 95%CI: 0.46–0.91, respectively). Conclusions: In a real-world primary care setting, the long-term use of GLP-1RAs and SGLT-2i, but not other GLDs, appeared to decrease the risk of incident CKD in T2DM, supporting a role in primary prevention of CKD.