A common diabetes drug may slow the progression of atrial fibrillation

Metformin, a drug that millions of people already take for diabetes may help protect the heart against a very common heart rhythm disorder. In a new study published in Circulation EP, researchers from the Department of Veterinary Clinical Sciences used horses as a translational animal model to show that metformin can slow the progression of atrial fibrillation (AF).

AF affects millions of patients worldwide and increases the risk of stroke, heart failure and early death. While current treatments can often restore normal heart rhythm in the short-term, the condition often returns. This is because AF gradually changes the heart itself, creating a self-perpetuating cycle that makes the disease increasingly difficult to treat. Breaking this cycle has become an important goal in recent AF research.

The results support the idea that targeting the heart’s metabolism could be a new way to prevent AF in patients at risk

Three years ago, a multidisciplinary group of researchers in Copenhagen, bringing together equine veterinarians, human cardiologists and basic scientists, set out to explore whether metformin could help prevent such AF-induced changes in the heart. Using a unique longitudinal horse model, they followed the same animals for four months as AF developed.

Horses treated with metformin were more resistant to developing AF and showed a more organised heart rhythm later in the disease course. These protective effects were linked to activation of the enzyme AMPK, a central energy regulator in the heart, and to changes in genes that control electrical signalling in the atria.

“Horses, like humans, are among the few species that naturally develop AF, and the disease is in fact also a common problem in racehorses,” says Professor and horse cardiologist Rikke Buhl, one of the principal investigators behind the study, and continues:

“We developed a new biopsy technique that allowed us to sample the heart repeatedly over time. This would be difficult in most animals, but because horses are large and calm, it can be done safely in standing horses”.

These were the tissue samples that formed the basis for a detailed molecular analysis of AF-induced changes.

Because metformin is already widely used, inexpensive and well tolerated in humans, the findings are potentially relevant beyond veterinary medicine.

The results support the idea that targeting the heart’s metabolism could be a new way to prevent AF in patients at risk. The study adds experimental support to growing clinical evidence suggesting that metformin lowers AF risk in humans.