A new experimental anti-obesity drug, Growth Differentiation Factor 15 (GDF15), improves diastolic heart function in mice with type 2 diabetes independent of its weight loss effects, suggesting the drug may work as a treatment to prevent the most prevalent form of heart failure in people with diabetes.
"I believe that if we manage this type of heart disease for the 400-million-plus people who have been diagnosed with type 2 diabetes worldwide - if we get on top of it for someone diagnosed in their 40s or 50s - then they won't have this type of heart failure in their 60s and 70s," said John Ussher, a professor in the Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada Research Chair in Pharmacotherapy of Energy Metabolism in Obesity and a member of both the Alberta Diabetes Institute and the Cardiovascular Research Institute. "It's debilitating for the patient because they get out of breath from just walking up one flight of stairs, and it's also a huge burden on the health care system."
Ussher's lab tested GDF15, which acts on the brain to decrease appetite and promote weight loss. It is currently in early clinical trials for use in humans.
The team gave GDF15 to mice with type 2 diabetes, while a control group lost weight through diet alone. The team found an improvement in diastolic heart function in both groups, but it was better in the mice that had received the drug. The research team determined that the drug caused this improvement because of its anti-inflammatory effects on the heart.
"One of the cell types that causes an inflammatory response in the heart is known as macrophages, and we saw fewer macrophages recruited to the heart," Ussher explained. "Several biomarkers of elevations in inflammation were decreased in the heart with GDF15 treatment "
The most common type of heart problem in type 2 diabetes is diastolic dysfunction, in which the heart does not relax properly between pumps. Symptoms include fatigue and shortness of breath. The problem, explained Ussher, is that patients who are newly diagnosed with type 2 diabetes do not often have their heart function tested because the focus of treatment is on blood sugar control through diet, weight loss and medication. This means patients with diabetes may live with diastolic dysfunction for many years without direct treatment. Later in life it can show up as an often fatal condition known as heart failure with preserved ejection fraction.
The next step for his research will be to investigate the mechanism behind how GDF15 reduces inflammation in the heart. The Ussher lab recently published another paper looking at an Ozempic-like drug called liraglutide, also known as Victoza, which they found also promotes weight loss and improves the heart's ability to relax.
Ussher notes that the weight loss impact of glucagon-like peptide-1 based drugs like Ozempic or Victoza is better than with GDF15, and studies suggest that the two drugs have synergistic actions and could be used together as complementary treatments.
The findings were reported in the paper, ‘Growth differentiation factor 15 alleviates diastolic dysfunction in mice with experimental diabetic cardiomyopathy’, published in Cell Reports. To access this paper, please click here
Commentaires