Semaglutide’s potential Beyond Metabolism: A Conversation with Dr. Mahmoud Elbatreek
Recent research suggests semaglutide, a GLP-1 receptor agonist, offers benefits extending beyond its well-known metabolic effects, specifically impacting cardiac and organ health.Pharmacy Times spoke with Mahmoud Elbatreek, PhD, about his study and the implications for treating heart failure with preserved ejection fraction (HFpEF).
Dr. Elbatreek’s work indicates semaglutide improves diastolic function and reduces fibrosis – the scarring that stiffens the heart - independently of weight loss. This finding shifts the understanding of GLP-1 receptor agonists, demonstrating “direct organ-protective actions” benefiting not only the heart, but also the liver and kidneys, aligning with recent drug approvals for chronic kidney and liver diseases. His team’s “multi-omics data” revealed the drug targets core disease pathways,rather than solely impacting metabolism.
Given that myocardial fibrosis is a key driver of HFpEF progression, the potential for semaglutide to address this directly is notable. Dr. Elbatreek explained that their study suggests initiating GLP-1 therapy early in the disease state could help prevent or slow adverse cardiac remodeling. This positions GLP-1 receptor agonists as possibly “foundational therapy” for HFpEF and other fibrotic diseases, broadening the potential patient population.
HFpEF remains a difficult condition to treat, and Dr. Elbatreek envisions a multifaceted role for GLP-1 receptor agonists. While weight loss is a substantial benefit, patient adherence can be hampered by gastrointestinal side effects. His research suggests a potential path forward: retaining cardiovascular efficacy while improving tolerability through dose adjustments.
Pharmacists,Dr. Elbatreek emphasized, should be aware of two key points. First, the cardiovascular benefits are driven by direct anti-fibrotic and organ remodeling actions, independent of weight loss. Second, future monitoring may need to expand beyond traditional A1C and BMI checks to include cardiovascular biomarkers like NT-proBNP, hs-CRP, and potentially novel fibrosis markers like endotrophin.
Looking ahead, Dr. Elbatreek outlined three crucial areas for future clinical research. He called for “de-escalation trials” comparing standard doses to lower, non-anorectic doses to assess if cardiovascular benefits can be maintained while minimizing GI distress. He also highlighted the need for trials evaluating whether lower doses can preserve skeletal muscle mass, as higher weight loss doses have been linked to muscle loss. he proposed head-to-head trials comparing the cardiovascular benefits of GLP-1 receptor agonists to bariatric surgery to determine if the drug offers advantages beyond weight reduction alone.
