a couple taking medication imageJuly 25 2018

Switching to sulfonylureas in type 2 diabetes has been linked with an increased risk of complications compared with staying on metformin, a BMJ study has concluded. However, the study has been challenged for suggesting the link is causal rather than just an association. 


The BMJ study researchers had set out to “assess whether adding or switching to sulfonylureas is associated with an increased risk of myocardial infarction, ischaemic stroke, cardiovascular death, all-cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy in patients with type 2 diabetes.”

Looking at patient data from between 1998 and 2013, the researchers analysed records relating to 77,138 people who had been initiated on metformin, and identified 25, 699 who had either had a sulfonylurea added or been switched to a sulfonylurea during the study period.

During an average follow-up period of 1.1 years, “sulfonylurea use (switching and adding combined) was associated with an increased risk of heart attack (7.8 v 6.2 per 1,000 person-years), all-cause mortality (27.3 v 21.5), and severe hypoglycaemia (5.5 v 0.7), compared with continuing metformin alone,” reported the BMJ.

“There was also a trend towards increased risks of ischaemic stroke (6.7 v 5.5 per 1,000 person-years) and cardiovascular death (9.4 v 8.1) with sulfonylurea use.

“Compared with adding sulfonylureas to metformin treatment, switching to sulfonylureas was associated with a greater risk of heart attack and all-cause mortality, but no differences were found for ischaemic stroke, cardiovascular death, or severe hypoglycaemia.”

The researchers concluded: “Sulfonylureas as second line drugs are associated with an increased risk of myocardial infarction, all-cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy. Continuing metformin when introducing sulfonylureas appears to be safer than switching.”

Challenging the conclusion, Professor Karim Meeran, Professor of Endocrinology at Imperial College Faculty of Medicine in London, described the statement “Continuing metformin when introducing sulfonylureas appears to be safer than switching” as “an unjustified and dangerous conclusion, and cannot be drawn from the data, which simply reports an association between stopping metformin and worse outcomes.”

Discontinuing the metformin and replacing it with a sulfonylurea could be due to a relative or absolute contraindication with the metformin, he said. “The conclusion potentially misleads readers in suggesting that sulfonylureas causally increase risk of heart disease.”

Links:
BMJ announcement      
A Douros et al. ‘Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: population based cohort study’. BMJ 2018;362:k2693. Published 18 July 2018.