A group of drugs commonly used for diabetes carry an increased risk of heart problems and death when compared with a different type of diabetes drug, researchers have found.
Their study found that people taking drugs called sulphonylureas are more likely to have heart attacks, heart failure or die, compared to people taking another popular diabetes drug called metformin. Doctors should choose metformin when treating people with diabetes, unless they can't take it or it doesn't work for them, say the researchers.
What do we know already?
If you have type 2 diabetes, it means you have too much glucose in your blood. This can damage your blood vessels, causing heart attacks and strokes, as well as damage to smaller blood vessels in your kidneys, feet, and eyes. Some people with type 2 diabetes control their blood glucose through diet and exercise, but most people need diabetes medicines.
The most commonly used drugs are metformin (brand name Glucophage), and a group of medicines called sulphonylureas. Sulphonyureas include the medicines chlorpropamide, glimepiride (Amaryl), glipizide (Glibenese, Minodiab), tolbutamide, glibenclamide (Daonil, Euglucon), and gliclazide (Diamicron).
Another group called glitazones (also known as thiazolidinediones) are also used. There are two types: rosiglitazone (Avandia) and pioglitazone (Actos).
These medicines all help keep your blood glucose under control, although they work in different ways.
Lately, there's been concern that some of these drugs might increase your chances of having a heart attack or getting heart failure (where the heart can't pump blood efficiently). It's hard to pick up these problems in the clinical studies that are done before drugs are licensed, because they may take a long time to happen, and you need to test very large groups of people to pick up these sorts of differences in risk.
This new study looked at the risks of having a heart attack, getting heart failure, or dying for any reason while taking one or more of the commonly used diabetes drugs. The researchers used figures from a big database of prescribing information, cross-checked with patient records. They compared each type of drug with metformin, because metformin is a well-established diabetes drug that tends to be used first for people with diabetes.
What does the new study say?
The study found that people were more likely to die of any cause, or to get heart failure, while taking a sulphonylurea drug, compared with while taking metformin. They were also more likely to have a heart attack, although this link was not as strong.
It's hard to say exactly how big the difference is. That's because the researchers analysed the results in different ways. Using one set of calculations, the researchers said sulphonylureas were linked to a 60 percent increased risk of death, while using another set, the increased risk was 24 percent.
Of the two glitazone drugs, pioglitazone seemed to be better than rosiglitazone, although the researchers say they need to see more studies to be sure of this. People were less likely to die of any cause while taking pioglitazone, compared with while taking rosiglitazone or metformin. Neither pioglitazone nor rosiglitazone was linked to more deaths or heart attacks than metformin, although rosiglitazone was linked to an increased chance of heart failure. Doctors are already warned not to prescribe rosiglitazone for people at risk of heart failure.
It's important to remember that the study didn't compare the drugs with no treatment. So, it didn't say that people were more likely to die while taking sulphonylureas compared with taking nothing at all. The study may simply show that metformin works better than sulphonylureas.
How reliable are the findings?
The good points of this study are that it covered a lot of people (more than 90,000) over an average of 7 years each. Because of the way the data was recorded, we can compare the risks and benefits of treatments as they're actually prescribed, taking account of the fact that people tend to take more than one drug, or move from one drug to another over time.
However, this makes it harder to account for all the different factors that could affect the results. For example, people might only take sulphonylurea drugs after they'd tried metformin, and it hadn't worked well enough for them, or because they have kidney disease (people with kidney disease can't take metformin). That might mean that people who took sulphonylureas were sicker than people who took metformin, so more likely to die of any cause.
Also, the study relies on all the information on the databases being correctly entered at the time. Because this was a 'real world' study, rather than set up by researchers from the start, there's likely to be more human error in terms of recording data than in a clinical trial.
Where does the study come from?
The study was done by a team of researchers based at Imperial College in London, UK. It was published in the BMJ (British Medical Journal). The study was not directly funded by anyone, although some of the researchers received grants from various research programmes.
What does this mean for me?
If you are taking a sulphonylurea drug, the results of the study might sound alarming. But they may be less alarming than they sound. The study doesn't show that these drugs are actively doing you harm. If they reduce your glucose levels, they protect you against potential problems with your eyes, nerve endings, and feet, as well as treating symptoms such as thirst and tiredness.
What the study shows is that they may not be reducing your overall risk of having a heart attack, heart failure, or dying for any other reason, compared with metformin. Previous studies have shown that metformin seems to reduce the chances of having a heart attack or dying in people with diabetes, especially if you're overweight.
Doctors in the UK are advised to prescribe metformin first for patients with diabetes, although they are told to consider a sulphonylurea in some groups of patients. According to national guidelines, sulphonylureas work faster, so may be used when a quick treatment is needed, and may also be more suitable for patients who are not overweight.
What should I do now?
All diabetes medicines protect against the problems you get from having too much glucose in your blood. It's important not to stop taking medicines without talking to your doctor first.
If you have diabetes and you haven't been treated with metformin before, it may be worth discussing this with your doctor, especially if you're overweight.
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