A new experimental anti-obesity drug has been found to improve heart function in mice with type 2 diabetes, independent of its weight loss benefits. This discovery by a University of Alberta researcher suggests that the drug could be an effective treatment for preventing a common form of heart failure in people with diabetes.
The findings were published in the journal Cell Reports.
John Ussher, a professor in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta, led the study.
Ussher holds the Canada Research Chair in Pharmacotherapy of Energy Metabolism in Obesity and is affiliated with both the Alberta Diabetes Institute and the Cardiovascular Research Institute.
“If we can manage this type of heart disease for the over 400 million people diagnosed with type 2 diabetes worldwide, we might prevent the development of heart failure later in life,” Ussher said. “Managing it in patients diagnosed in their 40s or 50s could mean avoiding heart failure in their 60s and 70s.”
Heart failure linked to diabetes often leads to shortness of breath, even with minimal exertion, and places a significant burden on healthcare systems, Ussher added.
The experimental drug, Growth Differentiation Factor 15 (GDF15), is designed to act on the brain to reduce appetite and promote weight loss. It is currently in the early stages of clinical trials for human use. Since obesity is a major risk factor for both type 2 diabetes and cardiovascular disease, the drug’s dual effects make it particularly promising.
In the study, Ussher’s team administered GDF15 to mice with type 2 diabetes. Another group of mice lost weight through diet changes alone. Both groups showed improved diastolic heart function, but the improvement was more significant in the mice that received the drug. Researchers attributed this to the drug’s anti-inflammatory effects on the heart.
“One type of cell that triggers an inflammatory response in the heart is called macrophages. We found fewer of these cells in the hearts of mice treated with GDF15,” Ussher said. “Additionally, several biomarkers associated with inflammation were reduced with the drug treatment.”
According to Health Canada, over three million Canadians—about 8.9% of the population—live with diabetes, and another 6.1% have prediabetes. The Canadian Diabetes Association notes that around 80% of people with diabetes will die from heart disease or stroke. The most common heart condition in people with type 2 diabetes is diastolic dysfunction, which occurs when the heart does not relax properly between beats, leading to symptoms such as fatigue and shortness of breath.
Ussher pointed out that newly diagnosed type 2 diabetes patients rarely have their heart function tested, as treatment typically focuses on blood sugar control through diet, weight management, and medication. As a result, many patients may unknowingly live with diastolic dysfunction for years, which can develop into a serious condition called heart failure with preserved ejection fraction later in life.
Ussher has dedicated his research career to finding treatments for this often overlooked aspect of diabetes. His next step is to investigate how GDF15 works to reduce inflammation in the heart.
In related research, Ussher’s lab recently studied another drug called liraglutide, known commercially as Victoza, which is similar to Ozempic. This drug also promotes weight loss and improves the heart’s ability to relax. Ussher noted that while glucagon-like peptide-1 (GLP-1) based drugs like Ozempic and Victoza are more effective at promoting weight loss compared to GDF15, studies suggest that the two types of drugs could work together, offering complementary benefits.
This promising research could lead to new treatments that address both obesity and heart failure risks in people with type 2 diabetes, potentially improving quality of life and reducing healthcare burdens worldwide.
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