Common diabetes drug may desensitize people to dangerous drop in blood sugar

• Sulfonylurea type 2 diabetes drugs are linked to a higher long-term risk of an impaired awareness of hypoglycemic episodes, according to a new study from Taiwan.
• From 5 years of use onward, the study suggests that repeated hypoglycemic events de-sensitize sulfonylurea users to the occurrence of hypoglycemic symptoms.
• Impaired hypoglycemic awareness with sulfonylureas was compared with that of insulin use, which conversely tapered off with time.

Sulfonylureas, a class of type 2 diabetes medications, are associated with higher risk of impaired awareness of hypoglycemia when used over the long term in a new study.

A recent study — published in Annals of Family Medicine — compared sulfonylureas with insulin treatment.

The study found that while both were linked to an increased chance of hypoglycemia (dangerously low blood sugar) in the short term, people taking sulfonylureas after 5 or more years were roughly three times as likely to have impaired hypoglycemia awareness.

Impaired hypoglycemia awareness (IHA) refers to a reduced capacity to detect when one’s blood sugar is too low, even dangerously low.

IHA may occur when years of repeated hypoglycemic episodes result in a psychological desensitization to its symptoms, and thus awareness of when it is occurring.

Sulfonylureas: Some of the oldest diabetes drugs in use

Sulfonylureas are among the oldest diabetes medications in use, discovered in 1946 and introduced clinically in 1956. They work by stimulating beta cells in the pancreas, promoting insulin production.

Sulfonylureas include drugs such as Glipizide , Glipizide ER, Glimepiride , and Glyburide, all of which are available in the United States. They are among the least expensive diabetes medications.

The new study, conducted in Tainan City, Taiwan, involved 898 people with type 2 diabetes. Of these, 65.1% were taking sulfonylureas, and 41.0% were taking insulin.

The researchers assessed IHA using two standard measures, the Gold and Clarke questionnaires . Their findings were roughly equivalent by both standards.

Sociodemographic characteristics including age, sex, education, marital status, residence, occupation, and living arrangement were accounted for, as well as disease and treatment histories, anti-hyperglycemic agent use, and self-reported diabetes-related medical care.

Both sulfonylurea and insulin users experienced IHA during their first years of treatment. For the former, IHA was present in 65.3% (according to the Gold questionnaire) and 51.3% (according to the Clarke questionnaire) of sulfonylurea patients. Among insulin users, the incidence was 41.0% (Gold) and 28.2% (Clarke).

At 5 years, however, IHA decreased among people taking insulin, while it increased to 70.7% (Gold) and 56.9% (Clark) among sulfonylurea users.

Why prescribe sulfonylureas over other diabetes drugs?

Jason Ng, MD, BA , teacher of endocrinology and metabolism in the Department of Medicine at the University of Pittsburgh, not involved in this study, explained why a physician might choose to prescribe a sulfonylurea medication instead of insulin.

“Insulin works by replacing the endogenous insulin when patients don’t make as much as they need to help control their blood sugars. In patients with higher sugars, insulin is indicated to help reduce their sugars significantly and fairly quickly.”

– Jason Ng, MD, BA

However, he said, “sulfonylureas can work better if the patient’s blood sugars are mildly elevated, and they may not want to take insulin injections daily.”

“Sulfonylureas work by stimulating the pancreas to produce insulin mostly and helping the endogenous insulin work better,” Ng further explained.

Even so, sulfonylureas and insulin are not the only medications available to people with type 2 diabetes these days, said Ng.

“Newer blood sugar control medications work by different mechanisms than sulfonylureas,” he said. “The newer medications do not work by stimulating the pancreas to make more insulin, and therefore do not carry the same risk of overstimulation of insulin leading to an increased risk of hypoglycemia.”

What are the signs of hypoglycemia?

To better understand when one is experiencing hypoglycemia, it is a good idea to be aware of its symptoms. Some of the most clinically important indicators that one is having a hypoglycemic episode are tremors, sweats, dizziness, hunger, headaches, and a change in mental status.

Other symptoms include:

• being nervous or anxious
• sweating, chills, and clamminess
• irritability or impatience
• confusion
• fast heartbeat
• nausea
• a loss of skin color
• sudden sleepiness
• feeling weak or having no energy
• blurred/impaired vision
• tingling or numbness in the lips, tongue, or cheeks
• coordination problems or clumsiness
• nightmares or crying out during sleep
• seizures.

How to prevent low blood sugar

Regardless of diabetes medication, the best strategy for avoiding adverse outcomes is checking in with a physician regularly.

Ng recommended that, to begin with, people do so “every 3 months if possible to ensure that the blood sugars are coming down effectively based on the medication prescribed, and then every 6–12 months once the sugar levels are stable and at goal.”

The authors of the study found that regular blood glucose testing and retinal scans were associated with lower rates of IHA in their participants.

A retinal scan allows a doctor to examine the back of the eye to monitor for diabetic retinopathy , which can occur when abnormally high blood sugar damages the retina’s small blood vessels.

Should people who take sulfonylureas worry?

While the study highlights an important association between sulfonylureas and the potential danger of experiencing hypoglycemia, its authors do note some limitations to their research.

First of all, all participants were residents of the same city, where prescriptions could be consistently refilled and taken, which is not always the case.

Secondly, they self-reported their medical care, and it was not possible for researchers to validate these reports against medical records. Thus, there is some concern that individuals may have over-reported the amount of care they received.

Finally, as in all such observational studies, while sulfonylurea and insulin use may have correlated to higher or lower rates of IHA, establishing a causal link was beyond the scope of the study.