January 23, 2017

Dangerous Sulfonylurea Side-Effects for Diabetes


by Dr. Scott Saunders, M.D.


Jan was almost a hundred pounds overweight. She came into my office because she was getting “tired spells,” headaches and severe fatigue that interfered with her work. Her doctor had put her on diabetes medications. But ever since then she had no energy and was getting these episodes. She was also horrified that she was gaining weight. Jan was worried what might happen to her if she continued taking these medications with such side-effects. She was hoping I could help get her off of them, even though her doctor said she would be on them for life.

After assessing Jan’s laboratory tests and medications, I reassured her that she did not need to take these medications for life. I could help her body and blood sugar return to normal. It turns out that she was given a medication that is commonly used in diabetes called glyburide, a sulfonylurea type medication that is known to cause all of these problems.

Sulfonylurea side effects What are Sulfonylureas?

The use of sulfonylurea medications to lower blood sugar began in the 1940s. It was found that sulfur-containing antibiotics would cause an increase in insulin from the pancreas. It wasn’t the sulfur, but the specific chemical antibiotics that blocked a certain calcium channel and caused excess insulin to be excreted in those who had insulin resistance.

The first generation of sulfonylurea drugs began to be marketed to those with high blood sugar in the 1950s. These include:

  • Chlorpropamide (Diabinese)
  • Tolazamide (Tolinase)
  • Tolbutamide (Orinase, Tol-Tab)

In the 1980s, the second-generation agents became available:

  • Glipizide (Glucotrol)
  • Glyburide (DiaBeta, Glynase, Micronase)

The last class of sulfonylurea drugs came in 1995.

  • Glimepiride (Amaryl)

Sulfonylureas lower blood sugar by causing a release of insulin from the pancreas. Thus, they require a working pancreas that can make insulin. Those with type 1 diabetes cannot benefit from this class of drugs.

Sulfonylurea Side-effects

Doctors often consider the desired effects of a medication, but downplay the side-effects. It is important to understand that all drugs are toxins and that they are not natural to the body. There is a desired part of toxicity – lowering blood sugar, for example – but there are other effects of toxicity that are undesirable.

When a sulfonylurea drug is introduced into the body, it targets not only the pancreas, but is distributed throughout every other system. It acts on a certain enzyme that affects how calcium enters the cells. So, wherever these calcium channels exist, the drug will block them, causing a certain effect. For example, nerve cells contain the same calcium channel so the sulfonylurea can damage nerve function.

Genetic differences increase susceptibility to the effects of sulfonylureas. Some people will get very ill. Others may die, while most are only mildly affected.

The “desired” effect of sulfonylureas is to increase insulin. However, there are several undesirable effects:

  • Hypoglycemia (low blood sugar)
  • Obesity
  • Increased hunger, especially craving carbohydrates

The sulfonylureas class of drugs can block the liver from making more glucose (sugar). The result is extremely low blood sugar. The low blood sugar causes people to feel weak, tired, get headaches and feel pain all over. They also start craving sugar, causing them to eat more…and create additional fat.

Weight Gain from Sulfonylurea

One of the worst side-effects of sulfonylureas is obesity. First, sulfonylureas stop fat cells from using fat for energy. Second, because sulfonylureas increase insulin, this fat is deposited into cells. Together, sulfonylureas create more fat cells that aren’t used, which increases obesity.

Higher insulin also causes more insulin resistance, which increases fat, making diabetes worse. As blood sugar gets higher, doctors often increase the dose of the medications. This causes further toxicity to the calcium in the cell, eventually leading to cell death.

There is evidence that these medications also worsen diabetes by killing the very cells that make insulin in the first place.[1] Some with type 2 diabetes progress to type 1 diabetes. When the pancreas no longer produces insulin, the sulfonylurea medications don’t work, and the patient needs insulin injections for life.

Besides causing obesity, higher insulin levels are also associated with worse outcomes. One study that compared the outcomes of several different treatment regimens concluded, “…insulin was associated with higher rates of death, major cardiac and cerebrovascular events, and microvascular disease.”[2] There is a direct association with high insulin to complications such as stroke, heart disease and death.

Other areas that are known to be affected by the toxicity of sulfonylureas include:

Chlorpropamide (a drug in the sulfonylurea class) seemed to have an effect on the protein production in the liver, but wasn’t found in one study to cause hepatitis, or damage liver cells.[3] Thus, it may not directly cause hepatitis, but indirectly kills liver cells by increasing insulin and causing excessive storage of glycogen and fatty liver disease.

The nerves are also affected indirectly by decreasing the energy available to them. Nerves are very sensitive to energy production, and when there is not enough energy, the nerve cells die, causing neuropathy, or numbness and tingling in the hands and feet, as well as Alzheimer’s disease.[4]

Sulfonylureas affect the energy production of the heart because of their effect on the chloride channels, creating fatal arrhythmias and death. Because of the risk of cardiovascular death, the FDA requires a warning label such as this on sulfonylurea medications:

sulfonylurea warningSULFONYLUREAS WARNINGS

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