Association of Glucagon-Like Peptide-1 Receptor Agonist vs Dipeptidyl Peptidase-4 Inhibitor Use With Mortality Among Patients With Type 2 Diabetes and Advanced Chronic Kidney Disease

Abstract

Importance: Glucagon-like peptide-1 (GLP-1) receptor agonist use is associated with reduced mortality and improved cardiovascular outcomes in the general population with diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used antidiabetic agents for patients with advanced-stage chronic kidney disease (CKD). The association of these 2 drug classes with outcomes among patients with diabetes and advanced-stage CKD or end-stage kidney disease (ESKD) is not well understood.

Objective: To assess whether use of GLP-1 receptor agonists in a population with diabetes and advanced-stage CKD or ESKD is associated with better outcomes compared with use of DPP-4 inhibitors.

Design, setting, and participants: This retrospective cohort study used data on patients with type 2 diabetes and stage 5 CKD or ESKD obtained from the National Health Insurance Research Database of Taiwan. The study was conducted between January 1, 2012, and December 31, 2018. Data were analyzed from June 2020 to July 2021.

Exposures: Treatment with GLP-1 receptor agonists compared with treatment with DPP-4 inhibitors.

Main outcomes and measures: All-cause mortality, sepsis- and infection-related mortality, and mortality related to major adverse cardiovascular and cerebrovascular events were compared between patients treated with GLP-1 receptor agonists and patients treated with DPP-4 inhibitors. Propensity score weighting was used to mitigate the imbalance among covariates between the groups.

Results: Of 27 279 patients included in the study, 26 578 were in the DPP-4 inhibitor group (14 443 [54.34%] male; mean [SD] age, 65 [13] years) and 701 in the GLP-1 receptor agonist group (346 [49.36%] male; mean [SD] age, 59 [13] years). After weighting, the use of GLP-1 receptor agonists was associated with lower all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.63-0.98) and lower sepsis- and infection-related mortality (HR, 0.61; 95% CI, 0.40-0.91). Subgroup analysis demonstrated a lower risk of mortality associated with use of GLP-1 receptor agonists compared with DDP-4 inhibitors among patients with cerebrovascular disease (HR, 0.33; 95% CI, 0.12-0.86) than among those without cerebrovascular disease (HR, 0.89; 95% CI, 0.71-1.12) (P = .04 for interaction).

Conclusions and relevance: Treatment with GLP-1 receptor agonists was associated with lower all-cause mortality among patients with type 2 diabetes, advanced-stage CKD, and ESKD than was treatment with DPP-4 inhibitors. Additional well-designed, prospective studies are needed to confirm the potential benefit of GLP-1 receptor agonist treatment for patients with advanced CKD or ESKD.

Figure.. Flowchart of Patient Enrollment

CKD-5 indicates stage 5 chronic kidney disease; DPP-4 inhibitor, dipeptidyl peptidase 4 inhibitor; ESKD, end-stage kidney disease; GLP-1 RA, glucagon-like peptide-1 receptor agonist; MACCE, major adverse cardiovascular or cerebrovascular event.