GLP-1 RAs Could Lower Mortality Risk in Type 2 Diabetes with Advanced CKD

Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was associated with a lower risk of mortality than use of dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes and advanced-stage chronic kidney disease (CKD), according to a new study.

Results of the study, which assessed risk of all-cause mortality as well as sepsis- and infection-related mortality, suggest use of GLP-1 RAs was associated with a 21% reduction in risk of all-cause mortality and also provide insight into the apparent effects in patient subgroups, including those with and without cerebrovascular disease.

“The 2 major findings of this study can be summarized as follows: use of GLP-1 receptor agonists in patients with diabetes and stage 5 CKD or EKSD was associated with lower all-cause mortality compared with use of DPP-4 inhibitors and use of GLP-1 receptor agonists was associated with lower sepsis- and infection-related mortality compared with use of DPP-4 inhibitors,” wrote investigators.

To better understand real-world effects of GLP-1 RAs and DPP-4 inhibitors in patients with diabetes and advanced-stage CKD or end-stage kidney disease (ESKD), a team led by investigators from the Kidney Research Institute at Chang Gung Memorial Hospital in Taiwan designed they current study as a retrospective cohort study using data from the National Health Insurance Research Database of Taiwan. Using a combination of ICD-9-CM codes, investigators sought to identify all patients with type 2 diabetes and stage 5 CKD or ESKD from 2012-2018.

From their search, investigators identified 75,557 patients. Of these, 48,277 were excluded because they did not use target medications or fulfilled elusion criteria, which included incomplete data, diagnosis of diabetes after enrollment, and diagnosis of major adverse cardiovascular and cerebrovascular events, receipt of dialysis, or death before index date. For the purpose of analysis, the index dates defined as 91 days after the first exposure to a GLP-1 RA or DPP-4 inhibitor.

Outcomes of interest for the study were differences in all-cause mortality, sepsis- and infection-related mortality, and mortality related to major adverse cardiovascular and cerebrovascular events among those receiving GLP-1 RAs and DPP-4 inhibitors in propensity score weighted analyses. Major adverse cardiovascular and cerebrovascular events included myocardial infarction, cardiogenic shock, heart failure, coronary revascularization, coronary artery bypass surgery, thrombolysis therapy, malignant arrhythmia, and stroke.

A total of 27,279 patients were identified for inclusion in the study, including 26,578 receiving DPP-4 inhibitors and 701 receiving GLP-1 RAs. Among the DPP-4 inhibitor cohort, 54.34% were male and the mean age was 65 (SD, 13) years. Among the GLP-1 RA cohort, 49.36% were male and the mean age was 59 (SD, 13) years.

Prior to prosperity score weighting, the DPP-4 inhibitor cohort was older, concentrated in rural areas, and included fewer patients receiving dialysis and more patients receiving an angiotensin-converting enzyme inhibitor, diuretics, and insulin than those in the GLP-1 RA cohort. Following prosperity score weighting, the DPP-4 inhibitor cohort included 26,568 individuals and the GLP-1 RA cohort included 603 individuals.

In weighted analyses, use of GLP-1 RAs was associated with a lower risk of all-cause mortality compared to use of DPP-4 inhibitors (HR, 0.79 [955 CI, 0.63-0.98]; P=.03). Results also indicated use of GLP-1 RAs was associated with a lower risk for sepsis- or infection-related mortality than DPP-4 inhibitors (HR, 0.61 [95% CI, 0.40-0.91]; P=.02). No significant difference was observed for risk of major adverse cardiovascular or cerebrovascular events with use of GLP-1 RAs compared with DPP-4 inhibitors (HR, 1.07 [95% CI, 0.76-1.51]; P=.69).

In subgroups analyses, results demonstrated the apparent reduction in risk observed for all-cause mortality with use of GLP-1 RAs compared with DPP-4 inhibitors was greater among those with a cerebrovascular disease (HR, 0.33 [95% CI, 0.12-0.86]) than those without cerebrovascular disease (HR, 0.89 [95% CI, 0.71-1.12]) (P=.04 for interaction).

This study, “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,” was published in JAMA Network Open.