GLP-1 Receptor Agonists Linked to Low Mortality in Diabetes, CKD Treatment

New data suggested treatment with glucagon-like peptide-1 (GLP-1) receptor agonists had associations with lower all-cause mortality among patients with type 2 diabetes (T2D), advanced-stage chronic kidney disease (CKD), and end-stage kidney disease (ESKD), compared to dipeptidyl peptidase-4 (DPP-4) inhibitors.

It additionally showed the use of GLP-1 receptor agonists was associated with lower sepsis- and infection-related mortality than DPP-4 inhibitors, but not lower major adverse cardiovascular and cerebrovascular events (MACCE)-related mortality.

“The different clinical benefits (ie, better glucose control, metabolic benefit) between GLP-1 receptor agonists and DPP-4 inhibitors might explain the better outcomes observed in patients treated with GLP-1 receptor agonists than in those treated with DPP-4 inhibitors,” wrote study author Huang-Yu Yang, MD, PhD, Kidney Research Institute, Department of Nephrology, Chang Gung University College of Medicine.

The retrospective cohort study assessed outcomes in this population constructed from data from the National Health Insurance Research Database (NHIRD) in Taiwan. Study data were collected between January 2012 - December 2018 and analyzed from June 2020 - July 2021.

Patients were prescribed either a GLP-1 receptor agonist or a DPP-4 inhibitor 3 months before the index data, with the index date defined as 91 days after the first exposure to either of the agents. The study identified primary outcomes as all-cause mortality after the index date during follow-up, with secondary outcomes including sepsis- or infection-related mortality and MACCE-related mortality.

A total of 75,556 patients with type 2 diabetes (T2D) and stage 5 CKD or ESKD were identified as receiving dialysis, with 48,277 subsequent exclusions, leading to a total of 27,279 patients in the study.

From that number, 26,578 participants were split into the DPP-4 inhibitor group (54.34% male; mean age, 65 years) and 701 in the GLP-1 receptor agonist group (49.36% male; mean age, 59 years). Following propensity score weighting, the DPP-4 inhibitor group consisted of 26,568 patients and the GLP-1 receptor agonist group consisted of 603 patients.

The rate of all-cause mortality was 7.95 per 100 person-years (95% CI, 7.76 - 8.15 per 100 person-years) in the DPP-4 inhibitor group and 6.10 per 100 person-years (95% CI, 7.76 - 8.15 per 100 person-years) in the GLP-1 receptor agonist group.

Data additionally show 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).

The rate of MACCE-related mortality was 2.56 per 100 person-years (95% CI, 2.45 - 2.67 per 100 person-years) in the DPP-4 inhibitor group and 2.64 per 100 person-years (95% CI, 1.75 - 3.53 per 100 person-years) in the GLP-1 receptor agonist group.

In the subgroup analysis, investigators observed a lower risk of mortality associated with the use of GLP-1 receptor agonists among patients with 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).

The 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.