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Many doctors still prescribe a class of drugs known as sulfonylureas for type 2 diabetes. These medications lower blood sugar levels, but at risk of making the underlying problem worse, and increasing the likelihood of death.

Sulfonylureas, a class of antidiabetes medications that includes tolbutamide (Orinase), glipizide (Glucotrol), glibenclamide, also known as glyburide (Micronase), and glimepiride (Amaryl), have been around for about 55 years. They are among the oldest, and therefore cheapest, best known, and widely prescribed medications for type 2 diabetes all over the world, surpassed only by metformin. 

Available in the US for $4 a month or less, they are a favorite for patients who don't have health insurance, and there's no doubt they work, at least at first. Over the long run, however, most sulfonylurea drugs probably cause as many health problems as they prevent.

What Does A Sulfonylurea Drug Do?

Medications in this class share a basic mode of action. They bind to a microscopic channel, something like a very tiny tube, on the surface of beta cells, the cells in the pancreas that produce insulin. This channel allows potassium to escape from the cell, and calcium to go in. When calcium invades the beta cell, it forms more of the immediate precursor of insulin. The proinsulin travels to a part of the beta cell known as a Golgi body, where it is broken down into "mature," usable insulin, and another protein called a C-peptide.
 
Taking medications such as Orinase, Micronase, Glucotrol, and Amaryl reliably lowers blood sugar levels in recently diagnosed type 2 diabetics. However, removing potassium from cells is not a good thing. When potassium goes out of a cell, sodium tends to come in, and more sodium goes into a cell than potassium goes out. This changes the cell's charge so that it is less able to respond to other substances, and since the sodium concentration in the cell has to be more or less constant to keep its charge stable, it becomes waterlogged. It swells.
 
The increased release of insulin also attracts the "attention" of the immune system, which sometimes generates antibodies that destroy insulin itself (which can result in a dire condition rather quickly), or antibodies that attack beta cells.
 
With continued use of sulfonylureas, beta cells tend to "burn out," so that more and more of the medication is required for them to produce less and less insulin. Sulfonylureas not only tend to become ineffective over time, they also tend to accelerate the progression from non-insulin-dependent to insulin-dependent diabetes. Older people, in particular, who start on sulfonylureas may find that they need insulin shots in just a few years. The effect is slower with some of the newer medications in this class, such as Amaryl, but lowering  blood sugar levels alone turns out not to be enough to maintain health.

What Else Can Go Wrong With Sulfonylureas?

Diabetics on drugs in the sulfonylurea class are quickly met with several dilemmas. Because the medications increase insulin production, they can also increase the risk of hypoglycemia, which may involve lapses of judgment, inexplicable emotions, dizziness, accident-prone behavior or actual accidents, and, in rare cases, coma and death. People learn that they need to eat a little more to prevent hypoglycemia. However, eating more has a downside, namely, the body needs more insulin. Moreover, since insulin keeps fat locked inside fat cells, weight becomes easy to gain and hard to lose. 
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