A Novel Agent Fails to Improve Outcomes in Diabetic Cardiomyopathy

Diabetes results in cardiac dysfunction. Individuals with diabetes are thus at elevated risk for developing heart failure (HF) and for adverse HF outcomes. Increased activity of the polyol pathway has been implicated in diabetic cardiomyopathy by reducing glucose to sorbitol, which is in turn metabolized to fructose, which induces myocardial tissue injury and fibrosis. In early-phase studies, the non–FDA-approved highly selective aldose reductase inhibitor AT-001, which inhibits the polyol pathway, was associated with improvements in natriuretic peptides and reductions in circulating sorbitol levels in individuals with diabetic cardiomyopathy. This manufacturer-sponsored, phase 3 trial (NCT04083339) was designed to assess the impact of AT-0…