The biggest and most comprehensive analysis of glucagon-like peptide-1 (GLP-1) receptor agonists on kidney and cardiovascular outcomes shows they have significant benefits in people with and without diabetes. Findings were published today in The Lancet Diabetes & Endocrinology.
Originally developed to treat diabetes, GLP-1 receptor agonists mimic the action of a hormone called glucagon-like peptide 1, which stimulates insulin production and lowers blood sugar levels. More recently, they have emerged as effective treatments for obesity — slowing digestion, increasing feelings of fullness, and reducing hunger.
But while the benefits of GLP-1 receptor agonists for the treatment of type 2 diabetes, obesity and cardiovascular disease are well known, their impact on chronic kidney disease (CKD) has been less certain.
Researchers conducted a meta-analysis of 11 large-scale clinical trials of GLP-1 receptor agonists involving a total of 85,373 people (67,769 people with type 2 diabetes and 17,604 people with overweight or obesity and cardiovascular disease but without diabetes). Seven different GLP-1 receptor agonists were investigated among the trials, including semaglutide (also known as Ozempic or Wegovy), dulaglutide (Trulicity) and liraglutide (Victoza).
The results showed that compared to placebo, GLP-1 receptor agonists reduced the risk of kidney failure by 16% and the worsening of kidney function by 22% (defined by a drop in estimated glomerular filtration rate — a measure of how much blood the kidneys filter clean every minute — of at least 50%). The combined reduction in the risk of kidney failure, worsening kidney function, and death due to kidney disease was 19%.
The analysis also confirmed previous findings that GLP-1 receptor agonists protect cardiovascular health, with a 14% reduction in the risk of cardiovascular death, non-fatal heart attack, and non-fatal stroke, compared to placebo. Death by any cause was 13% lower among patients treated with GLP-1 receptor agonists.
Lead author Professor Sunil Badve, Professorial Fellow at The George Institute for Global Health and UNSW Sydney said the study expanded current knowledge about this class of drugs in key areas, including benefits in people with CKD, and in people with and without diabetes.
“This is the first study to show a clear benefit of GLP-1 receptor agonists on kidney failure or end-stage kidney disease, suggesting they have a key role in kidney-protective and heart-protective treatment for patients with common medical conditions like type 2 diabetes, overweight or obesity with cardiovascular disease, or CKD,” he said.
“These results are particularly important for patients with chronic kidney disease. It is a progressive condition eventually leading to kidney failure requiring dialysis or kidney transplantation and is associated with premature death, mostly from heart disease. It has a significant impact on patients’ quality of life and incurs substantial healthcare costs.”
CKD is estimated to affect one in ten people worldwide, equivalent to around 850 million people. It is the tenth leading cause of death and is projected to become the fifth most common cause of death by 2050. Diabetes, cardiovascular disease and obesity are independent risk factors for CKD and represent a major global health burden.
Professor Vlado Perkovic, Professorial Fellow at The George Institute, Provost at UNSW Sydney and senior author on the study said, “This research shows that GLP-1 receptor agonists could play an important role in addressing the global burden of non-communicable diseases. Our study will have a major impact on clinical guidelines for the management of chronic kidney disease and cardiovascular disease in people with and without diabetes.”
“More work is now needed to implement the results of this study into clinical practice and improve access to GLP-1 receptor agonists to people who will benefit from them,” he added.