Metformin shows promise as treatment for HFpEF

Popular anti-diabetes drug metformin could have positive implications for heart failure patients, too, according to a recent study that found the medication reduced left ventricular stiffness in mice with heart failure with preserved ejection fraction (HFpEF).

The prevalence of HFpEF is growing on a global scale, first author Rebecca E. Slater and colleagues at the Sarver Heart Center at the University of Arizona wrote in the Journal of General Physiology—and it’s not slowing down anytime soon. By 2020, 8 percent of seniors over 65 are expected with be living with the condition.

“Unlike heart failure with reduced ejection fraction, pharmacological approaches to treating HFpEF do not currently exist, and earlier clinical HFpEF trials have been plagued by neutral results,” Slater et al. said. “Given the lack of effective HFpEF therapies, additional therapeutic approaches are of great interest.”

The team turned to metformin, a glucose-lowering drug that’s been shown in previous trials to increase left ventricular dilation and reduce the rate of heart failure in diabetics. They combined transverse aortic constriction surgery with deoxycorticosterone acetate supplementation to create a mouse model with HFpEF-like symptoms, then fed the mice metformin.

Rodents who received metformin showed reduced ventricular stiffness, allowing them to exercise more and allowing their hearts to contract more normally. Slater and coauthors said the result likely had a lot to do with titin, a protein that helps the heart muscle recoil after it’s been stretched.

“Although many other factors contribute to diastolic stiffness, titin appears to be a dominant factor,” the authors wrote. “This improvement in diastolic function is associated with improved exercise capacity and VO2 max, suggesting metformin preserves cardiac reserve and performance during exercise.”

They said their findings need to be replicated in human studies, but since metformin is already approved and well-tolerated in people, using it to tweak the stiffness of titin shouldn’t be a problem.

“This finding supports the importance of titin for left ventricular diastolic stiffness and adds to previous work in which titin was made either stiffer or more compliant and that revealed that left ventricular diastolic stiffness was altered accordingly,” Slater et al. wrote. “Metformin is a potential therapy for patients with HFpEF.”