The blockbuster GLP-1 obesity drugs also may protect the kidney and reduce the progression of kidney disease, a study led by researchers at Vanderbilt University Medical Center suggests.
In a gene-association study of more than 350,000 participants in the Million Veteran Program (MVP), a research initiative of the U.S. Department of Veterans Affairs (VA), higher expression of the glucagon-like peptide-1 receptor (GLP1R) gene was associated with a lower risk of kidney disease progression.
The report, published Oct. 25 in the journal JAMA Network Open, supports previous clinical trials that found the GLP-1 receptor agonist drug semaglutide reduced kidney disease progression in patients with Type 2 diabetes and chronic kidney disease.
“These findings are exciting because they suggest GLP-1 receptor agonists could have broader kidney-protective effects than initially thought,” said the paper’s first author, Jefferson Triozzi, MD, MSCI, instructor in Medicine in the Division of Nephrology and Hypertension at VUMC.
These drugs “could become part of the guideline-directed medical therapy to prevent kidney disease progression beyond the context of diabetes,” added the paper’s corresponding author, Adriana Hung, MD, MPH, professor of Medicine at VUMC and medical director of dialysis services at the Nashville VA Medical Center.
“However, it’s crucial to conduct more clinical studies to validate this potential across diverse patient groups, including emulation trials that can evaluate the effect of GLP-1 (receptor agonists) in different subgroups of the population usually not included in large trials,” Hung said.
An estimated 37 million Americans have chronic kidney disease, according to the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH).
Diabetes and high blood pressure are the two most common causes of kidney disease, which if not detected and treated early can lead to kidney failure — end-stage kidney disease — requiring dialysis or a kidney transplant.
Hung and her colleagues have made several important contributions to understanding the role of genetic and environmental factors, including inflammation and insulin resistance, in the development of chronic kidney disease.
A local site principal investigator for the MVP program, Hung also is principal investigator of an MVP grant exploring the genetics of kidney disease and hypertension. She co-chairs the MVP presentation and publication committee and the phenomics working group.
“These are exciting times for kidney care providers,” Hung said. The incorporation into guideline-directed medical therapy of new therapeutics targeting metabolic disturbances of chronic kidney disease provides an unparalleled opportunity to change outcomes for patients.
The current study was conducted with colleagues from Brigham and Women’s Hospital and the MVP Coordinating Center in Boston, the Atlanta VA Health Care System, and Emory University School of Medicine.
VUMC co-authors were Zhihong Yu, PhD, Ayush Giri, PhD, Hua-Chang Chen, PhD, Otis Wilson, T. Alp Ikizler MD, Elvis Akwo, MD, PhD, Cassianne Robinson-Cohen, PhD, and Ran Tao, PhD.
This work was supported by a Clinical Science Research and Development merit award and other awards from the VA, NIH grants T32DK007569, R01DK127083, R21AI156161 and U18DP006711, and by the Cystic Fibrosis Foundation.
