Use of real-world evidence data to evaluate the comparative effectiveness of second-line type 2 diabetes medications on chronic kidney disease

Chronic kidney disease (CKD) is a common complication of type 2 diabetes mellitus (T2DM). Approximately one-third of patients with T2DM also have CKD. In clinical trial studies, several anti-diabetic medications (ADM) show evidence of preventing the progression of CKD. Biguanides (e.g., metformin) are widely accepted as the first line medication. However, the comparativeness effectiveness of second line ADMs on CKD outcomes in T2DM is unclear. In addition, results from clinical trials may not generalize into routine clinical practice. In this study, we aimed to investigate the association of second line ADMs with incident CKD and CKD hospitalization in T2DM patients using real-world data from electronic health records. Our study found that treatment with sodium-glucose cotransporter 2 ( SGLT-2) inhibitors was significantly associated with a lower risk of CKD incidence in both primary analysis (hazard ratio, 0.43; 95% CI, [0.22;0.87]; p-value,0.02) (SU) as a second-line ADM. Treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor was significantly associated with lower CKD incidence (hazard ratio, 0.7; 95% CI, [0.53;0.96]; p-value, 0.03) and lower CKD hospitalization events (hazard ratio, 0.6; 95% CI, [0.37; 0.96]; p-value, 0.04) in the primary analysis. However, both associations were not significant in the sensitivity analysis. We did not observe significant association between use of GLP-1, TZD, insulin and CKD incidence or hospitalization compared to use of SU as the second-line ADM.