Sulfonylureas and Beta Cell Burnout

by Gretchen Becker Patient Expert

For years some diabetes authors have told us that the diabetes drugs known as sulfonylureas, often called just "sulfs," would burn out our beta cells. Beta cells are the cells in the pancreas that produce insulin.

I've occasionally come across comments in research papers that were consistent with that view, but nothing was ever terribly convincing. Sometimes the results suggested that the sulfs didn't cause burnout. For example, in the United Kingdom Prospective Diabetes Study (UKPDS) that was published in 1998, the rate of decline in blood glucose control was the same in the people taking sulfonylureas as in those taking metformin.

Unfortunately, The Lancet wants more than $30 to read the full text of the article, so you can't see the graphs yourself unless you have a lot of spare change sitting around.

However, the UKPDS was not designed to answer the question of beta cell failure, but to study complications, and the patients were advised to follow the low-fat, high-carbohydrate diet that was trendy at that time, so the diet might have had a greater impact on beta cell burnout than the drug.

Long ago, some researchers discovered that if you were trying to make an animal diabetic by using drugs like streptozotocin or alloxan, the drugs worked faster when you gave the animals lots of carbohydrates. Hence any effect of the sulfs might have been obscured by the diet.

Now a study designed to investigate this question has been published (full text of this one is $59). The researchers measured beta cell dysfunction in 504 patients with type 2 diabetes by measuring the levels of C-peptide, which is secreted by the beta cells along with insulin. They found that the duration of sulfonylurea treatment was the only factor independently associated with decreases in C-peptide concentrations.

In other words, the sulfonylureas do indeed seem to be associated with a more rapid decline in beta cell function.

Does this prove beyond a doubt that the sulfs burn out beta cells? No.

There are numerous different sulfonylureas, and some of them may have more effect than others. Other factors may also affect the results. And in order for an effect to be accepted, it should be replicated by several different research groups.

However, these results are consistent with the concept that sulfonylureas contribute to beta cell burnout.

Not long ago, the sulfs and insulin were the only possible treatments in addition to diet and exercise. And as other drugs like Glucophage (metformin) were added, they were expensive, whereas the sulfs were mostly generic and cheap. Furthermore, many physicians had been using the sulfs for years and were familiar with them and continued to feel comfortable prescribing them.

Today there are many possible treatments, and the drug metformin is now generic, so price alone should not force you to take a sulfonylurea. In addition to the possibility that the sulfs burn out beta cells, they can also, like insulin, cause hypoglycemia, because they stimulate your beta cells to produce insulin whether or not food is present. That forces you to eat even if you're not hungry so you don't go low. Not what you want if you're trying to lose weight, which most of us are.

So think carefully about what you want to do if your physician prescribes a sulfonylurea for you. There might be reasons to do so, for example, if you couldn't tolerate metformin and couldn't afford the more expensive drugs. Some newer sulfs are supposed to act for a shorter time, so the risk of hypoglycemia is less. But would still force your beta cells to secrete insulin.

The worst thing you can do is to avoid modifying your diet from what it was when you were diagnosed (unless you're a saint and were eating only minimal amounts of healthy food when diagnosed) and then expect a sulfonylurea to take care of your diabetes. That's a recipe for weight gain and rapid progression of your diabetes.

We're all different, and your decision might be different from my decision. The important thing is to be informed so you can make wise decisions.

Gretchen Becker
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Gretchen Becker

Gretchen wrote for HealthCentral as a patient expert for Diabetes.