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Abstract
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. 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. 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. Treatment with GLP-1 receptor agonists compared with treatment with DPP-4 inhibitors. 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. 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). 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.
Highlights
Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are contributors to the health burden and are associated with increased mortality and cardiovascular events.[1,2] Type 2 diabetes is the most common cause of CKD, and both diabetes and CKD are associated with increased all-cause mortality and increased rates of infection and cardiovascular events.[3,4] The high mortality among patients with diabetes and CKD or ESKD is mostly attributable to cardiovascular or infection-related events.[5,6] Both glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are associated with better blood glucose control, greater body weight reduction, lower mortality, and lower incidence of cardiovascular events in the general population with diabetes.[7-9]
The use of GLP-1 receptor agonists was associated with lower all-cause mortality and lower sepsis- and infection-related mortality (HR, 0.61; 95% CI, 0.40-0.91)
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
Summary
Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are contributors to the health burden and are associated with increased mortality and cardiovascular events.[1,2] Type 2 diabetes is the most common cause of CKD, and both diabetes and CKD are associated with increased all-cause mortality and increased rates of infection and cardiovascular events.[3,4] The high mortality among patients with diabetes and CKD or ESKD is mostly attributable to cardiovascular or infection-related events.[5,6] Both glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are associated with better blood glucose control, greater body weight reduction, lower mortality, and lower incidence of cardiovascular events in the general population with diabetes.[7-9]. The high mortality among patients with diabetes and CKD or ESKD is mostly attributable to cardiovascular or infection-related events.[5,6] Both glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are associated with better blood glucose control, greater body weight reduction, lower mortality, and lower incidence of cardiovascular events in the general population with diabetes.[7-9]. According to the American Diabetes Association guideline,[10] GLP-1 receptor agonist treatment is recommended for patients with diabetes and CKD who have an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 and are at risk for cardiovascular disease. According to the Kidney Disease: Improving Global Outcomes 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease,[11,12] GLP-1 receptor agonist treatment is suggested for individuals who are unable to use metformin or SGLT-2 inhibitors. Use of GLP-1 receptor agonists was associated with improved survival compared with use of DPP-4 inhibitors
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