At the American Heart Association Scientific Sessions 2025 in New Orleans, Mahmoud Elbatreek, PhD, postdoctoral scientist at Cedars-Sinai and professor of pharmacy at Zagazig University, discussed new findings demonstrating that GLP-1 receptor agonists such as semaglutide provide direct cardiovascular and multiorgan protective benefits independent of weight loss.
In a study evaluating early treatment in heart failure with preserved ejection fraction (HFpEF), semaglutide improved diastolic function, reduced myocardial fibrosis, and showed supportive effects in the liver and kidneys. The results highlight systemic anti-fibrotic and organ-remodeling mechanisms confirmed through multi-omics analysis.
Elbatreek emphasized that GLP-1 therapies may become foundational in HFpEF and other fibrotic conditions and recognized the vital role pharmacists will play in therapy optimization, biomarker-based monitoring, and improving patient adherence by balancing efficacy with reduced GI adverse effects. Future research aims to evaluate dose-de-escalation strategies, compare their effects with those of bariatric surgery, and ensure skeletal muscle preservation while maintaining cardiovascular benefits.
Pharmacy Times: Your study suggests that semaglutide improved diastolic function and reduced fibrosis independent of weight loss. How do these findings enhance our understanding of GLP-1 receptor agonists’ mechanisms beyond metabolic effects?
Mahmoud Elbatreek, PhD: Our findings enhance understanding of GLP-1 receptor agonists by demonstrating direct organ-protective actions independent of weight loss. We saw that semaglutide improved diastolic function and reduced fibrosis in the heart. Crucially, these benefits extend beyond the heart. The drug also benefits the liver and the kidneys, aligning with recent approvals of this drug in chronic kidney and liver diseases. Our multi-omics data confirmed this systemic effect by showing that semaglutide targets core disease pathways rather than simply modulating the metabolism.
Pharmacy Times: Given that myocardial fibrosis is a key driver of HFpEF progression, how might these preclinical antifibrotic findings translate into therapeutic strategies for patients with HFpEF in clinical practice?
Elbatreek: Myocardial fibrosis is the scarring that stiffens the heart. This is a key pathological driver of HFpEF. Our study suggested that semaglutide can reduce the progression or worsening of this fibrosis. In our study, the treatment began early in the disease state, and this suggested that initiating GLP-1 therapy earlier can help prevent or slow down the adverse cardiac remodeling. This means that GLP-1 receptor agonists become foundational therapy for HFpEF and other fibrotic diseases as well. This is exciting because it opens the door for using this drug in a broader population.
Pharmacy Times: Given that HFpEF remains challenging to treat, how do you envision the potential role of GLP-1 receptor agonists evolving in patient management, and what should pharmacists know about their mechanisms or monitoring considerations if used in this context?
Elbatreek: The role of GLP-1 receptor agonists is evolving to be multifaceted. While the weight loss benefit is huge, a significant percentage of patients stop these medications due to GI adverse effects. Our study proposes that this can be addressed by potentially retaining the cardiovascular efficacy while improving tolerability and patient adherence.
Pharmacists should recognize 2 key things. First, regarding the mechanism, understand that the CV benefit is driven by direct anti-fibrotic and organ remodeling actions, separate from weight loss. Second, regarding the monitoring, be aware that future monitoring may involve cardiovascular biomarkers like NT-proBNP, hs-CRP, and potentially novel fibrosis markers like endotrophin, rather than just monitoring A1C and body mass index.
Pharmacy Times: What future clinical research do you think is most needed to confirm these antifibrotic benefits in human populations and to help guide treatment selection or monitoring by clinicians and pharmacists?
Elbatreek: I think we need 3 things. First, those de-escalation trials comparing the efficacy of the standard dose versus the down-titrated non-anorectic dose to see if we can retain cardiovascular benefits while minimizing GI adverse effects. Second, trials must assess whether lower doses of GLP-1 receptor agonists preserve skeletal muscle mass, as higher weight loss doses are associated with muscle loss. Third, we need trials to compare the cardiovascular benefits of these drugs head-to-head with bariatric surgery to determine if the drug offers superior benefits beyond the effect of weight reduction alone.