Vascular health with glucagon-like peptide-1 receptor agonists

Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA), beyond their primary role in managing blood sugar and weight, demonstrate positive effects on vascular health. Studies suggest these medications can reduce the risk of cardiovascular events like heart attack and stroke and improve overall vascular function. This benefit is linked to various factors, including reduced blood pressure, improved lipid profiles, and anti-inflammatory effects within blood vessels.

The impacts of GLP-1 RA therapy on vascular health are mediated through many positive mechanisms. GLP-1 RA therapy reduces atherosclerosis by decreasing the formation of plaque in blood vessels, a major contributor to cardiovascular disease. It lowers systolic blood pressure by 2–5 mmHg and improves lipid profiles, including reductions in triglycerides and cholesterol. GLP-1 RA therapy also exerts anti-inflammatory effects, reducing inflammation within blood vessels, which is a crucial factor in the development of cardiovascular disease, and enhances endothelial function, improving its ability to regulate blood flow and prevent clotting. It promotes blood vessel repair through the production of cells involved in repairing damaged blood vessels. All these positive mechanisms culminate in a significant reduction in major adverse cardiovascular events, such as heart attack, stroke, and cardiovascular death.

Despite the limited expression of GLP-1 receptors in cardiac tissue, GLP-1 RAs tend to enhance myocardial function through multiple mechanisms, including optimizing coronary vascular smooth muscle cell function and endothelial function of the coronary microvasculature and peripheral vessels, in addition to improving blood glucose control and providing alternative energy substrates like ketones and lactate. At the level of vascular smooth muscle cells, they protect against pathogenic proliferative remodeling, thereby delaying plaque formation and stabilizing existing lesions. They also enhance cardiac mitochondrial function, leading to improved outcomes under hypoxic conditions and reduced pathological remodeling. GLP-1 RAs promote myocardial glucose uptake and utilization, reduce oxidative stress, and inhibit cardiomyocyte apoptosis. These mechanisms collectively provide cardioprotective effects on heart function and help prevent adverse cardiac remodeling.

Semaglutide, a GLP-1 RA, reduced the risk of major adverse cardiovascular events by 20% in people with overweight or obesity and established cardiovascular disease. Liraglutide improves blood circulation, increases nitric oxide levels, and inhibits factors that promote clotting.

The extent of vascular benefit can vary between individuals and different GLP-1 receptor agonists. These therapies are not a replacement for standard care but should be used in conjunction with other established treatments for cardiovascular disease and diabetes.

Dr. Mahir Khalil Ibrahim Jallo is an experienced Clinical Professor of Medicine with over 30 years of service in higher education institutions and as a Senior Consultant Endocrinologist. He currently serves as a Clinical Professor of Medicine and Senior Consultant in Internal Medicine, Diabetes, and Endocrinology at Gulf Medical University (GMU), UAE. He is also a faculty member at the Canadian Academy of Natural Health in Toronto, Canada. Dr. Jallo obtained his MBChB from Mosul Medical College in Iraq and holds a postgraduate Board Certification in Internal Medicine (CABM – equivalent to a PhD) from the Arab Board. He is a Fellow of the Royal College of Physicians of Edinburgh (FRCP Edin.), a Fellow of the Royal College of Physicians and Surgeons of Glasgow (FRCP Glasg.), and a Fellow of the American College of Endocrinology (FACE). He also holds a Diploma in Dyslipidemia from Boston University School of Medicine, USA. Since joining the JCI-accredited Thumbay University Hospital—the academic health center of GMU—in 2004, Dr. Jallo has played a pivotal role in establishing the Diabetes and Endocrinology services. He also serves as the Endocrinology Module Coordinator for the MBBS Program at GMU. Prior to relocating to the UAE, he served as an affiliated faculty member in the Department of Medicine, Mosul Medical College, and in the Department of Clinical Pharmacy at the Mosul College of Pharmacy, Iraq. Dr. Jallo is a regular invited speaker and active participant in numerous national and international conferences and CME programs. He is the founder and organizer of the annual GMU Diabetes & Endocrinology Conference since 2012 and has been a key organizing committee member in many international medical conferences. He is a member of editorial boards and a peer reviewer for several leading international journals in the field of Diabetes and Endocrinology, with numerous publications in peer-reviewed journals and conference abstracts. He also serves as a principal investigator in multiple national and international clinical research studies. Dr. Jallo is a distinguished member of many global medical societies, including the American Association of Clinical Endocrinology (AACE), the European Association for the Study of Diabetes (EASD), the International Society for Pediatric and Adolescent Diabetes (ISPAD), the European Society of Endocrinology (ESE), and the European Atherosclerosis Society (EAS). He has been honored twice with special awards in recognition of his outstanding contributions to Internal Medicine and Endocrinology, as well as for his dedicated service to the UAE community. He also has an extensive record of volunteer service supporting public health and education.