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Changing Completely to Second-line Type 2 Diabetic Drugs Increases Risk of Major Complications

Changing Completely to Second-line Type 2 Diabetic Drugs Increases Risk of Major Complications

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  • Sulfonylureas alone or sulfonylureas along with metformin was associated with an increased risk of complications compared to metformin alone
  • An increased risk was found in heart attacks, ischemic strokes, and all-cause mortality
  • Switching entirely to sulfonylureas increased the risk of heart attacks and all-cause mortality
  • The researchers advise continuing with the first drug of choice metformin when introducing sulfonylureas

For people with type 2 diabetes, changing their prescription of metformin to sulfonylurea drugs to control blood sugar levels puts them at an elevated risk of complications, finds a study in The BMJ today.

Know the Drugs for Diabetes

Metformin and sulfonylureas are prescribed only for type 2 diabetic patients whose bodies do not use the hormone insulin properly; insulin is needed to control the amount of sugar in the blood.

The drug metformin (popularly known by the brand name Glycomet in India) takes up that role and helps to control the amount of blood sugar by decreasing the amount of glucose absorbed from food and the amount of glucose made by the liver. Metformin can also increase the body's response to insulin. It is usually the first drug to be tried or the "first-line" therapy.


Sulphonylureas (tolbutamide, glimepiride, glipizide, glyburide) act primarily by stimulating the production and release of insulin and help the body's cells to use insulin better. They are most commonly prescribed as "second-line" therapy and mostly used in fixed-drug combinations with metformin especially in India due to compliance issues.

Although the safety of sulfonylureas has been extensively studied, doctors and scientists are still unaware about the specific risk of adding or switching to sulfonylureas compared with staying on metformin treatment alone.


A research team led by Professor Samy Suissa at McGill University in Canada analyzed data from the UK Clinical Practice Research Datalink for over 77,000 patients. All the patients (average age 64 years) had started on their metformin treatment for type 2 diabetes between the years 1998 to 2013.

The study assessed whether adding sulfonylureas to metformin or replacing metformin with sulfonylureas in type 2 diabetes patients had any association with an increased risk of serious complications. The control group continued on metformin alone.

The researchers then monitored admissions for heart attacks, ischemic strokes (that are caused due to an obstruction in a blood vessel), cardiovascular death, death from any cause also known as "all-cause mortality", and dangerously low blood sugar levels (severe hypoglycemia that may occur in diabetic patients who are on medications) by checking up the hospital records.

The scientists followed the patients for just over a year.

During this period they found out that
  • Compared with continuing metformin alone, the use of sulfonylurea (switching and adding combined) was associated with an increased risk of heart attack (7.8 v 6.2 per 1000 person-years), all-cause mortality (27.3 v 21.5), and severe hypoglycemia (5.5 v 0.7).
  • Between the two sulfonylurea groups, the group that switched completely to sulfonylureas had an increased risk of heart attack and all-cause mortality alone (and not the other complications) compared to the group that added sulfonylureas to metformin treatment
The researchers say that their results can be generalized to a vast extent and the large sample size allowed the calculation of precise estimates, although they cannot rule out the possibility that some of the observed risks may be due to other unmeasured (confounding) factors.

So, in general, sulfonylureas as second line drugs "are associated with an increased risk of myocardial infarction, all-cause mortality, and severe hypoglycaemia, compared to metformin therapy alone".

The researchers conclude that the associations with myocardial infarction and all-cause mortality "were driven by switching to sulfonylureas and not the addition of sulfonylureas," "Thus, in line with current recommendations on the treatment of type 2 diabetes, continuing metformin when introducing sulfonylureas is safer than switching."

This study "is well designed and the relationships appear strong and consistent and could be used to individualize treatment decisions and minimize harm."

Reference :
  1. Metformin - (https://medlineplus.gov/druginfo/meds/a696005.html)

Source: Medindia

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