GLP-1 Drugs Linked to Survival in Type 2 Diabetes With Renal Disease – Medpage Today
by Kristen Monaco, Staff Writer, MedPage Today March 7, 2022
For people with type 2 diabetes and kidney comorbidities, treatment with glucagon-like peptide-1 (GLP-1) receptor agonists held a meaningful mortality advantage over dipeptidyl peptidase 4 (DPP-4) inhibitors, according to an observational study.
In a propensity score-weighted analysis, these patients with comorbid advanced-stage chronic kidney disease (CKD) or end-stage kidney disease (ESKD) had a 21% lower risk for all-cause mortality when they were on a GLP-1 receptor agonist rather than a DPP-4 inhibitor (HR 0.79, 95% CI 0.63-0.98), reported Huang-Yu Yang, MD, PhD, of Chang Gung University College of Medicine in Taoyuan, Taiwan, and colleagues in JAMA Network Open.
In a subgroup analysis, the lower risk of death with GLP-1 receptor agonists was only seen in patients with cerebrovascular disease (HR 0.33, 95% CI 0.12-0.86), whereas those free of cerebrovascular disease didn’t see significant mortality protection (HR 0.89, 95% CI 0.71-1.12, P=0.04 for interaction).
The retrospective cohort study also found a 39% lower risk for sepsis- and infection-related mortality with GLP-1 receptor agonists (HR 0.61, 95% CI 0.40-0.91) in the overall study population, but no difference in mortality related to major cardiac and cerebrovascular events.
These outcomes are of particular importance because the “high mortality among patients with diabetes and CKD or ESKD is mostly attributable to cardiovascular or infection-related events,” Yang’s group pointed out.
While both GLP-1 receptor agonists and DPP-4 inhibitors are based on the incretin pathway, Yang’s group said these classes have shown very different clinical efficacy in the many prior studies comparing the two classes.
“Lower hemoglobin A1c levels, greater body weight reduction, improved β-cell function, improved cardiac function, and reduced albumin level were observed in randomized clinical trials comparing GLP-1 receptor agonists with DPP-4 inhibitors,” they wrote, adding: “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.”
FDA-approved DPP-4 inhibitors include sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina). Approved GLP-1 receptor agonists include dulaglutide (Trulicity), exenatide extended release (Bydureon, Byetta), semaglutide (Ozempic, Rybelsus), liraglutide (Victoza), and lixisenatide (Adlyxin).
This 27,279-person analysis collected patient data from the National Health Insurance Research Database of Taiwan on patients with both type 2 diabetes and comorbid stage 5 CKD or ESKD. CKD was defined based on administrative codes plus a prescription for erythropoiesis-stimulating agents, while ESKD was defined by requiring dialysis. A total of 26,578 individuals received a DPP-4 inhibitor versus 701 who received a GLP-1 receptor agonist.
In general, patients on a DPP-4 inhibitor tended to be older and live in more rural areas and were less likely to be on dialysis but more likely to be on an ACE inhibitor, diuretics, and insulin. However, the researchers used propensity score weighting for the final analysis, balancing all these covariates between the groups.
But due to the retrospective nature of the study, Yang’s group noted that they couldn’t account for other potentially confounding factors that may have played a role in these outcomes, such as blood glucose control, smoking status, body weight, estimated glomerular filtration rate, and degree of albuminuria.
Kristen Monaco is a staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.
The study was supported by grants from the Ministry of Science and Technology, Chang Gung Memorial Hospital, and the Maintenance Project of the Center for Big Data Analytics and Statistics at Chang Gung Memorial Hospital.
Yang and co-authors reported no disclosures.
JAMA Network Open
Source Reference: Chen J-J, et al “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” JAMA Netw Open 2022; DOI: 10.1001/jamanetworkopen.2022.1169.
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