Diabetes drug protects the heart via unexpected pathway
SGLT2 inhibitors, originally developed to lower blood sugar in diabetes, are known to protect the heart. But exactly how has remained a mystery. Research published in Science now identifies an unexpected mechanism deep inside human heart muscle.
SGLT2 inhibitors reduce the risk of heart failure, and this effect appeared even before blood sugar levels dropped. How they achieved this cardiac protection was unclear. The study, published in Science, shows that these drugs activate an enzyme in the human heart called pantothenate kinase (PANK), which plays a role in energy metabolism within heart cells.
Fuelling the heart muscle
Pantothenate kinase is involved in producing coenzyme A, a molecule that heart cells need to burn fats and sugars for energy. In heart failure, this metabolic process is disrupted. By activating PANK, SGLT2 inhibitors appear to support the energy supply of heart cells, independently of any effect on blood sugar.
This was measured directly in human cardiac tissue, which makes the finding more relevant than studies relying solely on animal models. That said, this is a mechanistic insight: the study demonstrates that the pathway exists and that the enzyme is activated. Whether this is the primary reason these drugs improve outcomes for patients requires further investigation.
Why this matters for longevity
Heart failure increases sharply with age and is a leading cause of loss of independence and death in older adults. Understanding how existing medicines protect the heart is valuable, especially when the mechanism is independent of blood sugar regulation. It also raises the question of whether PANK could be a target for new heart-protective agents.
For people without diabetes but with elevated cardiac risk as they age, this is a relevant signal: the biological pathway activated by SGLT2 inhibitors may be useful beyond diabetes management alone. Clinical studies addressing this broader application are ongoing.
Search terms to explore further: SGLT2 inhibitor heart failure mechanism | pantothenate kinase coenzyme A cardiomyocyte | cardiac energy metabolism aging