Researchers at Penn Medicine have uncovered how common diabetes medications could swiftly improve heart function by activating an enzyme essential for energy production, offering new avenues for heart failure therapy.
A common class of diabetes medicines may protect failing hearts by switching on a key energy enzyme inside heart cells, according to researchers at Penn Medicine.
The team, based at the Perelman School of Medicine at the University of Pennsylvania, says SGLT2 inhibitors directly activate PANK1, an enzyme that helps drive the production of coenzyme A, or CoA, a molecule heart cells need to turn nutrients into usable energy. The findings, published in Science, offer a molecular explanation for why these drugs can improve outcomes in heart failure so quickly, including in some patients without diabetes, Penn Medicine said.
Heart failure occurs when the heart cannot pump or fill properly, leaving organs short of oxygen-rich blood. In that setting, energy supply becomes a major problem: heart muscle needs a constant flow of fuel to contract and relax efficiently, yet that system is often disrupted. The Penn researchers found that SGLT2 inhibitors helped human heart tissue use several fuels more effectively and raised CoA levels, improving the ability of heart cells to do the work required for pumping.
The work also points to a possible reason the benefits can appear within days. According to Penn Medicine and EurekAlert, activating PANK1 improved both contraction and relaxation in human heart cells, while blocking the pathway reduced the effect. That strengthens the case that the enzyme is not just involved in the response, but may be a major part of it.
The implications could be significant for future drug development. Current SGLT2 inhibitors were first designed to lower blood sugar by acting on the kidneys, but they are now widely used in heart failure because they cut hospital stays and deaths. Researchers are interested in whether a medicine could be designed to target PANK1 more directly, potentially preserving the heart benefits while avoiding kidney-related side effects such as dehydration and urinary or genital infections. Still, the new findings do not prove that PANK1 explains every benefit of the drugs, and the researchers say heart failure is likely influenced by several overlapping mechanisms.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
