Research raises questions over safety of diabetes medication

University of Sydney research published in Diabetes Care has revealed a link between the Type 2 diabetes medication gliclazide and an elevated risk of hypoglycemia and cardiac distress.

Type 2 diabetes develops when the body becomes resistant to insulin or when the pancreas stops producing enough insulin, resulting in high blood glucose levels, known as hyperglycemia.

Gliclazide is in the sulfonylurea family of medications and works mostly by increasing the release of insulin, which lowers blood glucose. Left untreated, diabetes and hyperglycaemia pose major risks to key organs, including the heart, blood vessels, nerves, eyes and kidneys.

Medications belonging to the sulfonylurea class have long been linked to higher rates of hypoglycemic episodes in Type 2 diabetic patients and until now, gliclazide was thought to pose a low risk for hypoglycaemia. 

The study’s lead author Dr Tim Middleton of the University of Sydney says the new finding shows that even with gliclazide, a significant number of hypoglycemic events may still occur in clinical practice.

“Thirty percent of our gliclazide-treated participants experienced clinically significant hypoglycaemia over 48 hour-period of continuous blood glucose monitoring,” says Dr Middleton.

“More than 60 per cent of these hypoglycemic episodes occurred at night but nocturnal hypoglycaemia is often asymptomatic, hard to detect outside a clinical or research setting, and may therefore go untreated.”

“Our research also adds weight to a body of accumulating evidence that hypoglycaemia predisposes patients to cardiac arrhythmia and therefore raises the risk of adverse cardiac outcomes, including sudden cardiac death.”

The research also found similar results in a small cohort of patients treated with insulin.

Sulfonylurea-based diabetes drugs have been in clinical use for over 50 years; gliclazide has been on the Australian Register of Therapeutic Goods since 1999 and is the most commonly prescribed sulfonylurea in Australia today.

Dr Middleton says over the past few decades multiple new drugs to treat type two diabetes have been developed and he believes a re-evaluation of the drugs used in treatment would be appropriate.

“There has been much debate regarding the safety of sulfonylurea therapy over the years. Unlike the newer anti-diabetic pharmaceuticals, sulfonylureas have never undergone rigorous cardiovascular safety trials,” he says.

“That being said, sulfonylureas have been used effectively in the treatment of type two diabetes for many years across thousands of patients. However, in light of the development of new agents which have been shown to be safe from a cardiovascular perspective, clinicians should re-evaluate how sulfonylurea therapy is utilised in the treatment of type two diabetes.”

Sulfonylurea and Diabetes:

- Sulfonylurea is an organic compound that has been used as a basis for diabetes medications for over 50 years.

- Sulfonylurea-based drugs are used to lower blood glucose levels.

- Hypoglycemia occurs when a person’s blood glucose levels drop below a safe level and there isn’t enough glucose for energy production.

- Symptoms of hypoglycemia include blurred vision, headache, nausea, loss of concentration, shaking, excess sweating, fatigue and fainting.

- There is a link between hypoglycaemia and cardiac arrhythmia which can result in sudden cardiac death.