BY JOSEPH GUSTAITIS | DECEMBER 30, 2022
Metformin, the most popular blood sugar-lowering medicine in the world, seems to be turning out to be the Swiss Army knife of medications. In recent years, there have been reports that metformin appears to improve mitochondrial function in people with diabetes, that it can help in chronic kidney disease (CKD), and that it might lower the risk of death from COVID-19 in people with type 2 diabetes. Now, a new study has determined that metformin might serve as a treatment for atrial fibrillation (AF, an irregular or rapid heartbeat).
Metformin is what pharmacologists call a “repurposable” drug. Although it was developed to treat one condition, researchers have found it can be “repurposed” to treat others. The new report was published in the medical journal Cell Reports Medicine and was the work of researchers at the Cleveland Clinic who were specifically interested in studying the repurposability of metformin. According to Mina Chung, MD, senior author of the study, “Finding drugs or procedures to treat atrial fibrillation is difficult because of potential serious side effects. There is a significant need for new treatments for atrial fibrillation as there have been no new drugs approved in more than a decade.”
The research team used high-tech methods, including genetic sequencing, “data-based pharmacoepidemiologic analysis advanced computation,” and “human atrial tissue transcriptomics-based network proximity analysis.” “We evaluated,” they said, “the relationship in patients on metformin and AF onset using large-scale patient record data extracted from the Northwestern Medicine Enterprise Data Warehouse (NMEDW) between 2011 and 2021.”
Metformin found to target genes associated with atrial fibrillation
What they discovered was that metformin targets no fewer than 30 genes associated with atrial fibrillation, with direct effects on gene expression for eight of them. The research team began with a list of 2,800 FDA-approved medicines but cut it down by studying three sources: a map of interactions between proteins called an “interactom,” a network of genes associated with atrial fibrillation, and each drug’s molecular or genetic targets. Several drugs seemed promising, but metformin turned out to be the most likely to be of use as atrial fibrillation therapy.
Because of the high-tech methods the researchers applied to their analysis, they were able to make their discoveries with surprising speed. According to Feixiong Cheng, PhD, of the Cleveland Clinic’s Lerner Research Institute and co-senior author of the study, “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.” Or, as study co-author Jessica Castrillon Lai put it, “It’s not that we’ve found a new drug target where it takes 20 years to test this in individuals.”
One of the most encouraging aspects of the new research is that it might lead to fewer problems with side effects, a common result of AF treatment. Today, atrial fibrillation medications work by impacting the body’s electrical system, but an alternate approach may turn out to be equally effective but less likely to have side effects.
In a review of the Cleveland Clinic research for the Endocrinology Network website, Gregory M. Weiss, MD, commented, “While this approach may be alien to the average clinician and even the traditional bench scientist, it is clear that data analytics machine-based research is not only contributing to our field but also here to stay. The next step should be an observational study looking at patients taking metformin for diabetes or pre-diabetes and the prevalence of AF in this population. If an association is found clinically then prospective trials can begin. The authors have shown that new directions can be found without enrolling patients or wasting time pursuing an avenue that leads to a dead end. In essence, network medicine allows researchers to skip a step and go right to investigations with the greatest likelihood of uncovering novel treatments. This is an exciting prospect for clinicians and patients that suffer from AF and so many other conditions.”
Leave a Reply