Researchers have identified a drug that could help improve heart function in people with diabetes who have heart attacks.
Currently in clinical trials as a potential treatment for a form of anaemia, the medication could help diabetic hearts to recover and reduce their risk of developing heart failure, research suggests.
Blood supply to the heart is reduced or cut off during a heart attack, starving the heart of oxygen (hypoxia).
In diabetes, heart cells are less able to tolerate hypoxia and therefore die more quickly.
We’re hopeful that we’ve identified a drug that can address this unmet need and improve outcomes for people with diabetes after a heart attack
Dr Lisa Heather
Researchers from the University of Oxford have found that a drug, known as molidustat, can increase levels of a protein that helps cells to adapt and survive after being starved of oxygen.
They hope that giving molidustat to people with diabetes will help their hearts to recover after a heart attack and reduce their risk of further complications, such as heart failure.
Dr Lisa Heather, the British Heart Foundation (BHF) intermediate research fellow at the University of Oxford, said: “Even with optimal management, people with type 2 diabetes still have a higher risk of developing heart and circulatory diseases.
“They’re then more likely than people without diabetes to develop heart failure after a heart attack.
“Despite this, there are no treatments available to help the diabetic heart recover after a heart attack.
“We’re hopeful that we’ve identified a drug that can address this unmet need and improve outcomes for people with diabetes after a heart attack.”
Molidustat, which is taken orally, is currently in phase III clinical trials for treating anaemia in chronic kidney disease.
The drug works by increasing levels of a protein called hypoxia-inducible factor 1 (HIF).
When oxygen levels fall, HIF levels increase, causing it to activate its target genes which help cells to adapt and survive.
Previous research has found that people with diabetes have lower levels of HIF in their heart cells.
These promising results suggest that drugs which stabilise HIF could become a new treatment to reduce the risk of heart failure after a heart attack in people with diabetes
Professor Metin Avkiran, British Heart Foundation
Researchers found that when they exposed human heart cells with insulin resistance, a characteristic of type 2 diabetes, to low levels of oxygen, the increase in HIF protein levels was much lower than in control cells without insulin resistance.
However when insulin-resistant cells were treated with molidustat, the researchers saw increased levels of the HIF protein and activation of its target genes.
Next researchers looked at the impact of molidustat on heart function by exposing hearts from rats with and without type 2 diabetes to low levels of oxygen.
According to the study, the function of the diabetic hearts was significantly decreased after the period of low oxygen.
But when these hearts were treated with molidustat their function recovered back to the level of those without diabetes.
HIF is also involved in healing processes that happen after a heart attack, such as the growth of new blood vessels, a process known as angiogenesis.
Angiogenesis is known to be reduced in diabetic hearts, and this is believed to be a critical step in the development of heart failure.
In the study, when rats with type 2 diabetes were treated with molidustat the researchers saw increased levels of the signals involved in the growth of new blood vessels.
They hope the treatment could help to improve blood supply to the heart after a heart attack in people with diabetes.
Professor Metin Avkiran, associate medical director at the BHF, who funded the research, said: “These promising results suggest that drugs which stabilise HIF could become a new treatment to reduce the risk of heart failure after a heart attack in people with diabetes.
“Further research is now needed to translate these early stage findings into clinical benefit.”
The study is published in the journal Diabetes.