OBJECTIVES: There is a paucity of real-world evidence on the effectiveness of sodium-glucose 2 transporters (SGL2) inhibitors on the incidence of chronic kidney disease (CKD) compared to other glucose lowering agents. The present study examined the renal benefits of SGLT2 inhibitors in patients with type 2 diabetes relative to other glucose lowering agents.

METHODS: Retrospective cohort study was conducted among patients with diabetes using the All of Us research program. The primary outcome was the new onset of CKD in patients who took SGLT2 inhibitors versus other second-line anti-diabetes medications, including Glucagon-like peptide 1 receptor agonists (GLP-RA), dipeptidyl peptidase 4 inhibitors (DPP4i) and Sulfonylureas. The diagnosis of CKD is identified using concept sets “CKD due to type 2 diabetes or renal disorder due to type 2 diabetes”. Multinomial logistic regression was conducted to examine the association between the use of anti-diabetes medications and the occurrence of CKD over the follow-up period.

RESULTS: 8,787 patients were included in the analyses. The total proportion of patients with new onset of CKD was 21.6% across all medication groups. The odds ratio of CKD was 2.5 times higher in patients on GLP-RA 2.5[1.25-5.24, P=0.02] relative to SGLT2 inhibitor users. Patients on Sulfonylurea had a 2.5 times higher likelihood of CKD, 2.5[1.2-4.5, p=0.02]. For each unit increase in the blood urea nitrogen, the incidence of CKD increased by 14%,1.14[1.06-1.24, p<0.01]. The incidence of CKD decreased by 3% when the glomerular filtration rate increased by one unit, 0.97 [0.95-0.99, p=0.02].

CONCLUSIONS: Renal outcomes of SGLT2 inhibitors were better than other second-line anti-diabetes medications. The uptake of these medications should be ensured in diabetes patients to prevent CKD risk.