Sulfonylureas and beta cells

Patient Expert

Anyone interested in technical details of diabetes diagnosis and treatment might be interested in a recent supplement to the ADA journal Diabetes Care containing review articles summarizing the current state of mainstream thinking about various aspects of diabetes.

Not everyone agrees with mainstream thinking, but I think it's good to be aware of what it is so you can communicate better with your physician.

_  _

Unlike the usual situation with journal articles (with the exception of a few journals like PLOS), these review articles are free in full text. And there are lots of different topics.

One thing that interested me was several links to articles suggesting that the sulfonylurea drugs do, indeed, cause the death (apoptosis) of beta cells. You can find those here, here, and here. There is evidence that both the traditional sulfonylureas that keep working all day (thus forcing you to eat so you don't go low) and the newer versions that only work for a short time can harm the beta cells.

And interestingly, the drug exendin-4 seems to protect the beta cells from being destroyed by a sulfonylurea drug. Exendin-4 is a hormone found in the saliva of the Gila monster, and Byetta is a synthetic version of that hormone.

Some people, like Dr. Richard Bernstein, author of Dr. Bernstein's Diabetes Solution, have been saying for years that sulfonylureas wear out beta cells and make your diabetes worse after several years. But others have said there's no real evidence that the sulfonylureas "burn out" beta cells.

Even mainstream physicians admit that people who take sulfonylureas will "fail" the therapy after a few years, meaning the drugs no longer work, but they claim the problem is that type 2 diabetes is a progressive disease and it will get worse no matter what.

Type 2 diabetes often does progress when people continue to eat high-carbohydrate diets that stress the beta cells in the same way that the sulfonylureas do. The sulfonylureas bind to receptors on the beta cells that trigger insulin release through a series of steps. Glucose also triggers insulin release by means of the same receptors, so it's not surprising that both triggers would "wear out" the beta cells.

On the other hand, some people who have gone on low-carbohydrate diets say that their diabetes has not progressed much over the years.

One caveat about these studies showing beta cell failure after long-term use of sulfonylureas is that they've been done in cell cultures. Sometimes effects found in cell cultures aren't exactly replicated in a living body.

However, they're pretty suggestive. Now that other drugs like metformin, which is cheap as well as effective, are available, I think the sulfonylureas should be used only when there's no other option, for example if you can't tolerate metformin and you can't afford the more expensive drugs.

Controlling carbohydrates and using one of the less expensive insulins is another option.