Effects of sodium-glucose cotransporter-2 inhibitors on chronic kidney disease progression: a multi-state survival model

Abstract

Background: Current guidelines recommend good glycemic control in patients with type 2 diabetes (T2D) to limit the progression of associated complications with combination therapies. This study aimed to compare the rate of chronic kidney disease (CKD) progression between patients who did or did not receive sodium-glucose cotransporter-2 inhibitors (SGLT2i) using a multistate model with two intermediate states (i.e., CKD stage 4 (CKD4) and 5 (CKD5)) and one absorbing state (i.e., death). Methods: Data from patients with T2D and CKD stage 3 (CKD3) were retrieved for analysis. Patients treated with SGLT2i were matched 1:2 by prescription date with non-SGLT2i patients. The multistate model was constructed from Cox survival regression models specific to each transition stage. Cumulative failure and transition probabilities were estimated from bootstrapping. Results: Data from 6582 patients (2194 and 4388 patients in the SGLT2i and non-SGLT2i groups, respectively) were analyzed. At 10-year follow-up, patients in the SGLT2i group were more likely to remain at CKD3 compared to the non-SGLT2i group: 82.3% (95% CI 79.9%, 84.6%) vs 60.4% (57.6%, 63.4%). Transition probabilities to CKD4, CKD5, and death were lower in the SGLT2i group than non-SGLT2i group: 11.3% (9.5%, 13.3%) vs 19.8% (17.4%, 22.2%), 2.4% (1.5%, 3.4%) vs 7.4% (5.8%, 9.0%), and 4.1% (2.9%, 5.3%) vs 12.4% (10.3%, 14.6%), respectively. Conclusion: SGLT2i may delay the decline in renal function and slow CKD progression compared to standard care without SGLT2i.