Researchers set out to investigate how safe it is for patients with type 2 diabetes to switch from taking metformin, which is a standard "first-line" antidiabetic drug, to taking sulfonylureas, often prescribed to control blood sugar levels when metformin alone fails.
They were led by Prof. Samy Suissa, from McGill University in Quebec, Canada.
As Prof. Suissa and colleagues explain in their paper, numerous studies have confirmed the safety of sulfonylureas.
Fewer, however, have focused on their safety when patients have switched to the drugs or when they have added them to their previous treatment.
So, to fill this research gap, the scientists examined whether adding sulfonylureas or switching to them from metformin raises the risk of cardiovascular problems such as heart attack or stroke, or the risk of death from cardiovascular problems or from any other causes.
Also, the team examined whether or not switching to, or adding, sulfonylureas raised the risk of severe hypoglycemia, or low blood sugar. All these risks were compared with taking metformin alone.
Continuing metformin safer than switching
In order to study these links, the researchers examined over 77,138 people with type 2 diabetes who started taking metformin between 1998 and 2013.
Of these, 25,699 either added sulfonylureas to their treatment or switched to them altogether during the study period.
The team compared these people with age-matched controls who continued to take only metformin over a follow-up period of 1.1 years, on average.
Overall, when compared with staying on metformin, the study found that adding, or switching to, sulfonylureas was linked with a higher risk of a heart attack, death from any causes, and severe hypoglycemia.
More specifically, people adding, or switching to, the second-line treatment were 26 percent more likely to have a heart attack, 28 percent more likely to die from any causes, and over seven times more likely to have severe hypoglycemia, on average.
The researchers also discovered a trend toward a higher likelihood of stroke and death from heart problems in those switching to, or adding, sulfonylureas.
Finally, when comparing just adding sulfonylureas to metformin with switching to sulfonylureas completely, the latter raised the risk of a heart attack by 51 percent and mortality from all causes by 23 percent.
However, no differences were found in the risk of stroke, cardiovascular death, or hypoglycemia between just adding the drugs and switching to them.
Prof. Suissa and colleagues conclude, "Sulfonylureas as second-line drugs are associated with an increased risk of myocardial infarction, all-cause mortality, and severe hypoglycemia, compared with remaining on metformin monotherapy."
"Thus, in line with current recommendations on the treatment of type 2 diabetes, continuing metformin when introducing sulfonylureas is safer than switching."
As with any observational study, causality cannot be inferred from the results. But researchers Lucy D'Agostino McGowan and Christianne Roumie deem the study "well designed and the relations [...] strong and consistent" in an accompanying editorial, which is also published in the BMJ.