Use of Glucose-Lowering Medication in Patients with Chronic Kidney Diseases and Type 2 Diabetes

Abstract

Selecting effective and safe glucose-lowering medications for chronic kidney disease (CKD) patients is challenging. Pharmacokinetics of various glucose-lowering medications are altered and some medications lose effectiveness as kidney function declines, necessitating dosage adjustments or discontinuation. Findings from the general population in use of glucose-lowering medications are commonly extrapolated. But few studies have examined utilization of glucose-lowering medications and safety issues in real-world populations of CKD patients. To address the current knowledge gap with newer glucose-lowering medications in real-world data, this study evaluated three aims. Aim 1 identified that use of metformin and newer glucose-lowering medication classes (dipeptidyl peptidase 4 inhibitors [DPP-4i], glucagon-like peptide-1 receptor agonists [GLP-1RA], sodium-glucose cotransporter 2 inhibitors [SGLT2i]) in CKD patients showed statistically significant upward trends. However, prescription of these newer glucose-lowering medications was low in 2016. GLP-1RA and SGLT2i were only used in 6.1% and 3.3% in patients with CKD and type 2 diabetes, respectively, in 2016. Aim 2 identified disparities in use of SGLT2i and GLP-1RA in CKD patients. Black race was associated with a significantly lower rate of SGLT2i and GLP-1RA use, while Hispanic ethnicity and Asian race were associated with a significantly lower rate of GLP-1RA use compared to Whites. Compared with CKD stage 3 patients, CKD stage 4-5 patients were associated with lower odds of starting SGLT2i or GLP-1RA than sulfonylureas. Patients with cardiovascular disease or hyperlipidemia were more likely to start SGLT2i or GLP-1RA. Aim 3 showed that use of newer glucose-lowering medications (SGLT2i or GLP-1RA) when compared with sulfonylureas use was associated with decreased risk of hypoglycemia resulting in healthcare utilization. These results add to limited observational evidence for the association of newer glucose-lowering medications compared with sulfonylureas with safety issues among patients with reduced kidney function. Black and older patients with CKD were less likely to receive these newer agents, were more likely to receive sulfonylureas, which have higher risk for hypoglycemia, and were also at significantly higher risk of developing hypoglycemia after adjustment for other medications and covariates.