Recent research carried out at the University of Arizona in the United States examined the effectiveness of a diabetes drug, metformin, to treat heart failure.
There are different types of heart failure, one of which is referred to as heart failure with preserved ejection fraction (HFpEF). Approximately half of all patients with heart failure have the HFpEF form. This means that their hearts can contract, but because of stiffness in the lower left chamber, the heart cannot relax properly between beats. This reduces the heart’s ability to fill up with blood. This results in symptoms including shortness of breath and difficulty when exercising. It has been estimated that by 2020, HFpEF will affect over 8% of individuals over the age of 65.
There are no treatments currently available for this type of heart failure. HFpEF is more commonly seen in women and those individuals with risk factors such as hypertension, old age and being overweight.
Researchers at the Sarver Heart Center at the University of Arizona examined the effectiveness of metformin as a treatment for HFpEF. The reasoning behind choosing this drug was because the drug has already been shown to increase dilatation of the lower left chamber of the heart, also known as left ventricular dilatation, and thus decreases the rate of heart failure in diabetic patients. During this study, mice with HFpEF symptoms were given metformin and the results showed that the drug decreased left ventricular stiffness, and the mice were able to exercise.
This study, which was published in the Journal of General Physiology, demonstrates the ability of metformin to relax a particular protein, called titin, in the heart muscle. It is the relaxation of this protein that allows the heart to fill up with blood correctly before it is pumped around the rest of the body.
Titin works like a spring and aids the muscle to recoil following being stretched, and its stiffness can be modified by enzymes that add a phosphate group to a particular part of the titin. This section of the titin protein is called N2B, and it contains fewer phosphate groups in HFpEF patients, and this makes the titin very stiff. However, the researchers of this study found that treating these patients with metformin leads to an increase in the number of phosphate groups in the N2B section, which means the protein and thus the heart muscle becomes more compliant.
Henk L. Granzier at the Sarver Heart Center at the University of Arizona commented on their findings in a recent press release saying, “…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.”
Written by Jade Marie Evans, MPharm, Medical Writer
References:
- Slater , R.E. Metformin improves diastolic function in an HFpEF-like mouse model by increasing titin compliance. 2018. Journal of General Physiology. [Online]. [4 January 2019]. 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]. [4 January 2019]. Available from: https://www.eurekalert.org/pub_releases/2018-12/rup-ddc121918.php
