The biggest and most comprehensive analysis of glucagon-like peptide-1 (GLP-1) receptor agonists on kidney and cardiovascular disease shows these drugs have significant benefits in people with and without diabetes. In both types of patients, the combined reduction in the risk of kidney failure, worsening kidney function, and death due to kidney disease was 19%. The study also confirmed that GLP-1 receptor agonists protect cardiovascular health.
The benefits of GLP-1 receptor agonists for type 2 diabetes, obesity, and cardiovascular disease are established, but their impact on chronic kidney disease has been less certain.
“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 [chronic kidney disease],” said lead author Sunil Badve, professorial fellow at The George Institute for Global Health and UNSW Sydney.
The findings were published this week in The Lancet Diabetes & Endocrinology.
Originally developed to treat diabetes, GLP-1 receptor agonists mimic the action of glucagon-like peptide 1, which stimulates insulin production and lowers blood sugar levels. More recently, these drugs have emerged as effective treatments for obesity—slowing digestion, increasing feelings of fullness, and reducing hunger.
These researchers looked at kidney disease and cardiovascular disease. They conducted a meta-analysis of 11 large-scale clinical trials of GLP-1 receptor agonists involving a total of 85,373 people. The study included: 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 used, including semaglutide (Ozempic or Wegovy), dulaglutide (Trulicity), and liraglutide (Victoza).
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 study 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. In fact, death by any cause was 13% lower among patients treated with GLP-1 receptor agonists.
“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,” said Badve.
Chronic kidney disease is estimated to affect one in ten people worldwide, or 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 kidney disease and represent a major global health burden.
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.”
