US Pharm. 2022;47(11):1.

Cleveland Clinic researchers have identified a common diabetes medication, metformin, as a possible treatment for atrial fibrillation (AFib). The study, published in Cell Reports Medicine, built on ongoing collaborative Cleveland Clinic research to support further investigation into metformin as a drug-repurposing candidate. Researchers used advanced computation and genetic sequencing to determine that metformin’s targets overlap significantly with genes dysregulated in AFib.

“Finding drugs or procedures to treat atrial fibrillation is difficult because of potential serious side effects,” said Mina Chung, MD, senior author of the study who is in Cleveland Clinic’s Department of Cardiovascular Medicine in the Heart, Vascular and Thoracic Institute. “There is a significant need for new treatments for atrial fibrillation, as there have been no new drugs approved in more than a decade.”

“It’s not that we’ve found a new drug target where it takes 20 years to test this in individuals,” said Jessica Castrillon Lal, the study’s first author.

“We can cut off 10+ years in the drug development pipeline. We already have the information there. We just have to test it in a very computationally efficient way, such as artificial intelligence technology,” said Feixiong Cheng, PhD, co–senior author of the study.

The analysis found metformin targeted 30 genes associated with AFib, with direct effects on gene expression for eight. Eight other candidate drugs surfaced in the analysis, but researchers were able to identify metformin as the most promising candidate.

Ms. Castrillon Lal conducts research in Dr. Cheng’s laboratory, which uses network medicine approaches to find candidate drugs for repurposing, creating vast networks of molecular interactions. For this study, researchers winnowed down a list of 2,800 FDA-approved treatments by analyzing three data sources: a map of interactions between proteins called an interactome; a network of genes associated with AFib; and each medicine’s molecular or genetic targets.

AFib is the most common type of heart arrhythmia in the world and can lead to complications, including stroke and heart failure. Treatments have been primarily directed toward trying to prevent the arrhythmia using drugs targeting the electrical system, including ion channels in the heart, or using catheter ablation to isolate the pulmonary veins where initiating beats of AFib occur. Side effects, limited success, and potential complications, however, can limit these approaches.

In this Diabetes focus issue, the article “Investigating Cardiovascular Benefits of SGLT2 Inhibitors” (page 17) reports that another diabetes drug class may benefit patients with other common cardiovascular diseases: atherosclerotic cardiovascular disease and heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the authors write, appear to decrease overall morbidity and mortality in these patients.

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