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.
What Are Reasonable Alternatives To Sulfonylureas For Diabetes?
A more serious issue with the use of sulfonylureas is that people who take them are more likely to have fatal heart attacks, much more likely to have fatal heart attacks, in fact. One study found that users of tolbutamide (Orinase) were up to 522 percent more likely to die of a heart attack than diabetics who control their blood sugars with diet and exercise.
Another study found that switching to metformin really wasn't the answer, either. Metformin use resulted in about 8 percent more deaths from heart attacks than tolbutamide, although the risk of hypoglycemia (which can also result in death) was about 57 percent lower with metformin.
If you have type 2 diabetes, and you don't have a lot of money for medication, what can you do?
- Meglitinide drugs (which act very similarly to sulfonylurea drugs but have a shorter period of activity) are safer than sulfonylurea. They are still "pills" for treating diabetes, very easy to use, and not especially expensive (at least when compared to insulin). Gliclazide (which isn't available in the USA) and repaglinide (sold as Prandin in the USA) are relatively heart-safe. However, because they are relatively short-acting, they are less likely to help keep your blood sugar levels down if you snack between meals.
- When American researchers looked at the health records of 230,000 veterans receiving healthcare through the US Veteran's Administration, they found that metformin (which is equally effective and inexpensive) was linked to fewer heart attacks, strokes, and deaths than any sulfonylurea drug.
- Glipizide (Glucotorl) and glyburide (Micronase) raise the risk of heart attack by stimulating beta-receptors on the heart, forcing it to work harder. If you happen to be taking a blood pressure medication in the beta-blocker class in addition to your diabetes medication, the increased risk of heart attack they pose is lower. However, taking beta-blockers can make it more difficult to recognize the early symptoms of hypoglycemia. The solution is to test blood sugar levels often.
- Sulfonylurea drugs are actually better for diabetics who have a form of diabetes known as MODY, or maturity onset of diabetes of the young. This form of the disease can attack people who are thin and active, and usually is found in people who are normal weight or underweight. In MODY, the problem isn't an inability to make insulin. It's an inability to "release" or secrete insulin. Sulfonylureas restore the ability of beta cells to release insulin into the bloodstream, without causing them to "burn out" due overstimulation. However, even in MODY, long-term results tend to be better with metformin.
It's a good idea for your doctor to test you for the MODY genes when you are first diagnosed with diabetes. If you have it, you can start taking these inexpensive, well known drugs and expect good results.
If you don't, you can skip sulfonylurea treatment and go straight to other treatments that are more likely to work for you, bypassing the increased risk of heart attack, stroke, and death.
Sometimes type 2 diabetes really can be controlled by diet and exercise, that is, very strict diet, and exercise that includes strength training as well as cardio. Very few diabetics actually control their diets closely enough to make a difference, or get the right kind of exercise. If your doctor prescribes a sulfonylurea drug, however, ask questions, and make sure that whatever you are doing for diabetes you know the results by testing, testing, and testing some more, taking your blood sugar levels at home as often as your doctor recommends.
Sources & Links
- Christianne L. Roumie et al. Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus: A Cohort Study. Ann Intern Med., 6 November 2012
- 157(9):601-610.
- Photo courtesy of frankieleon via Flickr: www.flickr.com/photos/armydre2008/3672112456
- Photo courtesy of cogdogblog via Flickr: www.flickr.com/photos/cogdog/19075009156