Research on Metformin for Heart Failure Treatment

Overview of Heart Failure with Preserved Ejection Fraction (HFpEF)

Recent studies conducted at the University of Arizona have focused on the diabetes medication metformin as a potential treatment for heart failure. One specific type of heart failure examined is heart failure with preserved ejection fraction (HFpEF), which affects approximately half of all heart failure patients. In HFpEF, the heart can contract effectively; however, stiffness in the lower left chamber impairs its ability to relax between beats, limiting blood fill. Symptoms of this condition often include shortness of breath and exercise intolerance. It is projected that by 2020, over 8% of individuals aged 65 and older will be affected by HFpEF. Currently, there are no established treatments for this condition, which is more prevalent among women and individuals with risk factors such as hypertension, advanced age, and obesity.

Study on Metformin’s Effectiveness

Researchers from the Sarver Heart Center at the University of Arizona investigated the effects of metformin on HFpEF. The rationale for selecting this drug stems from its previous demonstration of promoting left ventricular dilatation, which in turn decreases heart failure rates among diabetic patients. In this study, mice exhibiting HFpEF symptoms were administered metformin, resulting in a decrease in left ventricular stiffness and improved exercise capacity.

Mechanism of Action

The findings, published in the Journal of General Physiology, reveal that metformin aids in the relaxation of a specific protein called titin within the heart muscle. This relaxation is crucial for allowing the heart to fill adequately with blood before pumping it throughout the body. Titin functions similarly to a spring, enabling the muscle to recoil after being stretched. In HFpEF patients, the stiffness of titin is altered by enzymes that modify phosphate groups on a critical segment known as N2B. In these patients, the N2B region contains fewer phosphate groups, leading to increased stiffness. The research indicates that metformin treatment enhances the number of phosphate groups in this section, resulting in greater compliance of the titin protein and subsequently the heart muscle.

Implications for Treatment

Henk L. Granzier from the Sarver Heart Center commented on the significance of these findings, stating, “Metformin is a potential therapy for patients with HFpEF. Because the drug is already approved and well tolerated in humans, using it to target titin stiffness presents a unique opportunity for immediate translation to the clinic.”

References

– Slater, R.E. Metformin improves diastolic function in an HFpEF-like mouse model by increasing titin compliance. 2018. Journal of General Physiology. [Online]. Available from: http://jgp.rupress.org/content/early/2018/12/19/jgp.201812259
– Eurekalert. 2018. Diabetes drug could be used to treat common heart failure syndrome, study suggests. [Online]. Available from: https://www.eurekalert.org/pub_releases/2018-12/rup-ddc121918.php