Professor Melanie Davies, Director of the National Institute for Health and Care Research Leicester Biomedical Research Centre (BRC), played a central role in new study which has shown that the weight loss drug semaglutide may benefit a group of heart failure patients who have had few specific treatment options previously available to them.
Professor Davies was the sole female non-cardiovascular specialist in the team of researchers on this international study, the results of which have been recently published in the New England Journal of Medicine.
Patients on the study who have heart failure with preserved ejection fraction and a BMI of over 30, and who were given the medicine over the course of 52 weeks lost on average 11% of their bodyweight, compared to those on a placebo, or ‘dummy’ drug. Furthermore, they showed fewer symptoms of heart failure, as measured by tests such as how far they could walk in six minutes.
Heart failure with preserved ejection fraction (HFPEF) makes up at least half of all cases of chronic heart failure.
Patients with this type of heart failure experience an especially high burden of debilitating symptoms, physical limitations, and poor quality of life.
Despite this burden, and the significant death rate associated this type of heart failure, there have been limited breakthroughs in its management. Treatment has mostly focussed on health problems linked to the condition, such as hypertension, elevated body mass index (BMI), metabolic syndrome, and ageing.
Professor of Diabetes Medicine, and Director of the NIHR Leicester BRC, Melanie Davies CBE, said: “Evidence gathered in recent years suggests that obesity plays a causal role in heart failure with preserved ejection fraction.
“This is through a complex pathway* whereby excess fat triggers insulin resistance, leading to inflammation that ends with changes to the heart that define this condition.
“Up to now, there have been no specific medical therapies to treat people experiencing obesity and this type of heart failure, highlighting a major and urgent unmet global healthcare need.”
The trial included 529 adults who had symptomatic heart failure and BMI of 30.0–34.9 kg m−2, 35.0–39.9 kg m−2 and ≥40 kg m−2.
Over the course of 52 weeks the participants received either 2.4mg of semaglutide once weekly (administered subcutaneously) or a placebo.
Professor Davies said:
“When compared the outcomes of the patients who received a placebo, we observed significant improvements in those who received the weekly semaglutide.
“They reported significant improvements in the symptoms and physical limitations associated with their heart failure. We also observed a reduced body weight of approximately 11% over the 52-week treatment period in this group, and a large improvement in how far they could walk in six minutes – an average of 20.3 metres further than those who received the placebo.”
There were also fewer heart failure hospitalizations or urgent visits among the semaglutide patients (1 compared to 12 events in those who received the placebo).
Professor Davies concluded:
“The impact of semaglutide we observed in this study represents a major advance for patients with heart failure with preserved ejection fraction (HFPEF) and obesity.
“Given that semaglutide is currently available and approved for the treatment of obesity, we believe that this data can be readily translated into clinical care, especially if followed by additional regulatory approvals and if the guidelines concurrently support such a recommendation.”
A second trial in people with Type 2 diabetes will follow soon and further add to the evidence.
*Visceral adiposity triggers insulin resistance and immune dysregulation, which eventually lead to macrophage polarization, upregulation of endothelial adhesion molecule expression, and B and T cell dysfunction, culminating in sustained local and systemic inflammation and altered myocardial metabolism.
These cellular defects result in the development of plasma volume expansion; endothelial dysfunction and coronary microvascular dysfunction; myocardial fibrosis, steatosis, and aberrant remodeling; abnormal skeletal muscle composition and function; ectopic epicardial and pericardial fat deposition; and pericardial constraint, resulting in reduced left ventricular (LV) compliance, diastolic dysfunction, atrial remodeling, and impaired hemodynamics, which define the HFpEF condition.
Link to paper: Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity | NEJM