Diabetes drug prevents heart attacks

Developing new drugs is extremely costly: the estimate test-tube to needle time for a new agent is ten years and the price tag is billions. But, it might not always be necessary to invent a new drug if you can find an existing drug that happens, as a side effect, to have a beneficial effect on the heart, which is what Ify Mordi, from the University of Dundee, has done with the diabetes drug metformin. Katie Haylor spoke with him...

Ify - Metformin is used  a treatment used for Type 2 diabetes. It reduces insulin resistance, causes you to lose weight and this is obviously beneficial in terms of your general health. It also is associated with improvements in the metabolism of the heart. One of the pathways that we do know about and is more well understood is that metformin acts on a substance called AMPK, which is Activated Protein Kinase. This substance is involved in molecular signalling within the heart and is associated with the fibrosis and enlargement of the heart muscle. Metformin reduces this and, therefore, this is one reason why it may have beneficial effects on the heart.

Katie - First of all, how do you go about linking a drug that’s being used routinely in diabetes with a heart condition?

Ify - Numerous studies have been done which have shown that metformin is beneficial in patients with diabetes and large studies, including done in the UK, have shown that metformin use in patients with diabetes is associated with reductions in heart attacks. In fact, in one study there was a striking 33 percent reduction in heart attacks and strokes in patients using metformin compared to other diabetes drugs.

So this suggested to us that perhaps metformin was having beneficial effects on the heart muscle. What we wanted to do was to try and translate this to use this in patients without diabetes. It’s something that hasn’t been done before and this is the really exciting bit of our research.

Katie - So how do you go about doing that then?

Ify - The research was done in two parts, and the first part was to look at electronic health records of patients that were using metformin that has a condition which predisposes to thickening of the heart muscle called “aortic stenosis.” This is a condition where there is narrowing of the main heart valve that lets blood out of the heart. This increase in pressure causes the heart to have to do more work. The heart muscle thickens up, which includes fibrosis and scarring of the heart muscle.

Katie - Okay. So take us back to your study.

Ify - The first part of the study was a retrospective study where we looked at people with this condition called “aortic stenosis.” In this condition, diabetes is associated with worse outcomes, so people with diabetes and this thickening of the heart muscle are more likely to die because of this. And what we found was that the diabetic patients in the study on metformin had a similar outcome as the patients who were not diabetic. In contrast, diabetic patients who weren’t taking metformin had a 44 percent increased likelihood of having a heart attack or a stroke that lead to death. This suggested to us that metformin use was associated with better outcomes and less likelihood of dying of a heart problem.

Katie - Presumably now you need to do this with people who don’t have diabetes at all, so is that what you did next?

Ify - Yes, exactly. What we did in this study, which was called “The MET REMODEL Study,” was to look at patients with previous heart attacks, and they also had thickening of the heart muscle. One group were given metformin treatment for a year and the other group were given placebo, and we studied the thickening of the heart muscle at the start of the study and at the end of the study after one year.

What we found was that the patients in the metformin group had twice as much reduction in the heart muscle size compared to the patients in the placebo group, proving for the first time in humans that metformin use was associated with the reduction in this adverse thickening of the heart muscle.

Katie - What happens next then?

Ify - This has provided us with some evidence that metformin could be used in this purpose. What we need to do now is to look at this in a large group of patients to see if this truly does lead to improvements in heart attacks and strokes in patients without diabetes.