Why Taking Sulfonylurea Drugs Could Be a Problem

Patient Expert
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The oldest type of type 2 diabetes drugs—known as sulfonylureas—are still widely used to treat type 2 diabetes. Sulfonylurea drugs should not be taken, however, by patients who have been diagnosed with type 2 diabetes who have latent autoimmune diabetes in adults, or LADA. Because LADA is frequently overlooked and undiagnosed, many patients with LADA are unaware they have the condition, and their doctors continue to treat them for type 2 diabetes.

About sulfonylurea drugs

Sulfonylurea drugs help to stimulate insulin production and came on the market in the 1950s to treat type 2 diabetes. Sulfonylurea drugs include:

  • glyburide (Diabeta, Glynase, Micronase)
  • micronized glyburide (Glynase Prestabs)
  • glipizide (Glucotrol)
  • glipizide extended-release (Glucotrol Xl)
  • glimepiride (Amaryl)
  • gliclazide (Diamicron)
  • chlorpropamide (Diabinese)
  • tolazamide (Tolinase)
  • tolbutamide (Orinase, Tol-Tab)

When appropriately used, sulfonylurea drugs are generally safe and effective for people with type 2 diabetes. The subset of patients who should not take these drugs, however, are those who have the autoimmune type of diabetes, known as LADA. According to the U.S. Centers for Disease Control's National Diabetes Statistics Report, 2017, 21.0 million Americans have a diagnosis of type 2 diabetes. Recent research estimates that from 10 to 15 percent of people with type 2 diabetes - from 2.1 to 3.15 million - may actually have LADA.

About LADA and sulfonylurea drugs

LADA is similar to type 1 diabetes in that it is an autoimmune disease, where antibodies attack and eventually destroy the insulin-producing beta cells in your pancreas. The main difference is that type 1 diabetes tends to strike rapidly, is more common in children and young adults, and results in immediate insulin-dependence. LADA usually appears in adults. With LADA, the destruction of beta cells happens more slowly, and it can be months or several years before someone with LADA becomes insulin-dependent. In contrast, many people with type 2 diabetes never need insulin or become insulin-dependent only after years or even decades of treatment.

According to diabetes researchers and experts, sulfonylureas should not be used as first-line therapy in patients with LADA. The reason? Research shows when someone with LADA takes a sulfonylurea drug, the drugs actually speed up the process of destruction of the pancreatic beta cells; which is sometimes called "beta cell burnout." As a result, you progress more rapidly to insulin-dependence.

The challenge

While it’s clear that people with LADA should not be treated with sulfonylurea drugs, there is a complication: most people with LADA don’t know it, and their doctors have diagnosed — and are treating them for — type 2 diabetes.

Could your type 2 diabetes be LADA?

Some factors and signs suggest that your type 2 diabetes may be LADA. These include:

  • You are slim, of normal weight, or only slightly overweight.
  • You have been diagnosed with another autoimmune disease – especially Hashimoto’s thyroiditis, Graves’ disease, and/or celiac disease.
  • You have a personal history or family history of another autoimmune disease.
  • You initially responded to type 2 diabetes treatment and lifestyle changes, but these approaches are increasingly less effective.
  • Your blood sugar is not well-managed with type 2 treatment, and you have a higher hemoglobin A1C or fasting glucose level.
  • You are being treated with insulin for your type 2 diabetes.

Unfortunately, when your type 2 diabetes gets progressively worse, doctors rarely suspect LADA. Instead, they assume that you are not following your treatment and recommended lifestyle changes. Identifying those people with LADA who are being treated for type 2 diabetes becomes even more important for patients taking sulfonylurea drugs, because of the potential for rapid beta cell destruction and earlier insulin-dependence.

Testing for LADA

If you have any of the factors or signs that put you at higher risk of LADA, you may have to request that your doctor test you for LADA. There are two types of tests—antibody tests and C-peptide levels—that can diagnose LADA.

Antibody Tests: There are four different antibody tests associated with autoimmune diabetes, but the most common antibodies in LADA are glutamic acid decarboxylase (GAD) antibodies. A normal GAD autoantibody level is less than or equal to 0.02 nmol/L. When you have elevated GAD antibodies, that is evidence of autoimmune diabetes. The other antibodies that can confirm a LADA diagnosis include islet cell autoantibodies (ICA), tyrosine phosphatase–related islet antigen 2 (IA-2), and insulin autoantibodies (IAA). All four antibody tests are typically negative in someone with type 2 diabetes.

C-Peptide Test: C-peptide, an amino acid chain in your blood, is a byproduct of the formation of insulin. Measuring C-peptide levels can assess your degree of pancreatic dysfunction. The reference range for C-peptide is from 0.8 to 3.85 ng/mL. C-peptide levels are usually normal or even high in people with type 2 diabetes. Low C-peptide levels are considered evidence of low insulin production and beta cell destruction consistent with LADA and type 1 diabetes.

Your next steps

Whether or not you are taking a sulfonylurea drug, if you have any of the risk factors or signs of LADA, ask your doctor to test you for LADA. If a LADA diagnosis is confirmed, your doctor can switch you from a sulfonylurea drug to other drug treatments and provide targeted and effective treatment that will help you better manage your diabetes.