Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Discontinuation in Patients with CKD

Background: Little is known about the association of discontinuation of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA) with outcomes in patients with chronic kidney disease (CKD). Methods: We identified adults with CKD stages 3-4 from 2005-2022 in the Veterans Affairs healthcare system. Individuals with an incident prescription for SGLT2 inhibitors or GLP-1 RAs were included, with the first fill date considered the index date. Factors associated with time to first treatment discontinuation, defined as an interruption in SGLT2 inhibitor or GLP-1 RA prescription for ≥90 days, were studied using Cox proportional hazards regression models. Associations of discontinuation 90-179 days and ≥180 days with death, myocardial infarction, coronary revascularization, hospitalization for heart failure, and ischemic stroke were assessed using Cox proportional hazards regression. Results: Of 96,345 individuals who received an SGLT2 inhibitor and 60,020 who received a GLP-1 RA, at least one discontinuation occurred in 35,953 (37%) of SGLT2 inhibitor users and 28,407 (47%) of GLP-1 RA users. SGLT2 inhibitor users were 24% Black, 71% White, 71% age ≥70, and 84% with CKD stage 3a. GLP-1 RA users were 20% Black, 75% White, 63% age ≥70, and 81% with CKD stage 3a. Black race, Hispanic ethnicity, cerebrovascular disease, peripheral vascular disease, and ischemic heart disease were associated with discontinuation of both drug classes. Female sex and more advanced CKD stage were also associated with SGLT2 inhibitor discontinuation. SGLT2 inhibitor discontinuation ≥180 days was associated with death, (adjusted hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.58-1.77) and heart failure hospitalization, (adjusted HR 1.26, 95% CI 1.13-1.40). GLP-1 RA discontinuation ≥180 days was associated with death, (adjusted HR 1.97, 95% CI 1.87-2.07), myocardial infarction (adjusted HR 1.23, 95% CI 1.11-1.36), heart failure hospitalization (adjusted HR 1.48, 95% CI 1.33-1.64), and ischemic stroke (adjusted HR 1.24, 95% CI 1.14-1.35). Conclusions: SGLT2 inhibitor and GLP-1 RA discontinuation was common and associated with harmful outcomes in adults with CKD.