The largest and most comprehensive analysis of glucagon-like peptide-1 (GLP-1) receptor agonists on renal and cardiovascular outcomes shows that they have significant benefits in people with and without diabetes. The 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 subjects (67,769 subjects with type 2 diabetes and 17,604 subjects with overweight or obesity and cardiovascular disease but without diabetes). Seven different GLP-1 receptor agonists were investigated between 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 fall in estimated glomerular filtration rate – a measure of how much blood in the kidneys clean the filter every minute – at least 50%). The combined risk reduction 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, nonfatal heart attack, and nonfatal stroke, compared with placebo. Death from 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 in renal failure or end-stage renal disease, suggesting that they have a key role in nephroprotective and cardiac therapy for patients with common medical conditions such as 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 that eventually leads to kidney failure requiring dialysis or a kidney transplant and is associated with premature death, mainly from heart disease. It has a significant impact on patients’ quality of life and entails significant health care costs.”
CKD is estimated to affect one in ten people worldwide, which equates to approximately 850 million people.2 It is the tenth leading cause of death and is expected to become the fifth leading cause of death by 2050.3 Diabetes, cardiovascular disease and obesity are independent risk factors for CKD and represent a significant global health burden.4
Professor Vlado Perkovic, Professorial Fellow at The George Institute, Provost at UNSW Sydney and senior author of the study said: “This research shows that GLP-1 receptor agonists could play an important role in tackling the global burden of non-communicable diseases The study will have an important 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 translate 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.
