Progression to symptomatic heart failure is a complication of type 2 diabetes; heart failure onset in this setting is commonly preceded by deterioration in exercise capacity.The study sought to determine whether AT-001, a highly selective aldose reductase inhibitor, can stabilize exercise capacity among individuals with diabetic cardiomyopathy (DbCM) and reduced peak oxygen uptake (Vo2).

A total of 691 individuals with DbCM meeting inclusion and exclusion criteria were randomized to receive placebo or ascending doses of AT-001 twice daily. Stratification at inclusion included region of enrollment, cardiopulmonary exercise test results, and use of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists. The primary endpoint was proportional change in peak Vo2?from baseline to 15 months. Subgroup analyses included measures of disease severity and stratification variables.

The mean age was 67.5 ± 7.2 years, and 50.4% of participants were women. By 15 months, peak Vo2?fell in the placebo-treated patients by –0.31 mL/kg/min (P?= 0.005 compared to baseline), whereas in those receiving high-dose AT-001, peak Vo2?fell by –0.01 mL/kg/min (P?= 0.21); the difference in peak Vo2?between placebo and high-dose AT-001 was 0.30 (P?= 0.19). In prespecified subgroup analyses among those not receiving sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists at baseline, the difference between peak Vo2?in placebo vs high-dose AT-001 at 15 months was 0.62 mL/kg/min (P?= 0.04; interaction?P?= 0.10).

Among individuals with DbCM and impaired exercise capacity, treatment with AT-001 for 15 months did not result in significantly better exercise capacity compared with placebo.?

Glucose concentrations are often elevated in?diabetics?and aldose reductase has long been believed to be responsible for diabetic complications involving a number of organs. Aldose reductase inhibitors?have been developed for the treatment of secondary complications in diabetes. The?aldose reductase inhibitors?inhibit or reduce secondary complications induced by diabetes, specifically in tissues in which glucose uptake is not insulin-dependent (probably neural tissue, the lens, and glomeruli). However, according to the results from the ARISE-HF study, although a similar theory has been established for diabetic cardiomyopathy, the results are not very bright. Nevertheless, it is important to recognize the risk of heart failure in patients with diabetes earlier and initiate treatment before the disease progresses.