Montreal—Replacing metformin with a sulfonylurea in type 2 diabetes (T2D) patients increases the risks for complications, a new study cautions.

A better approach, according to the report in The BMJ, is to add the sulfonylurea to metformin.

The advice from McGill University–led researchers has widespread application because metformin is the most commonly used first-line therapy for T2D, with sulfonylureas most frequently used as the second-line treatment, the study points out.

Noting few studies on the specific risk of adding or switching to sulfonylureas versus metformin monotherapy, the study team analyzed data from the UK Clinical Practice Research Datalink for more than 77,000 T2D patients, averaging age 64 years, who initiated metformin treatment between 1998 and 2013.

Researchers identified patients who subsequently added or switched to a sulfonylurea and then matched them to similar patients who continued metformin alone. Admissions for myocardial infarction, ischemic stroke, cardiovascular death, or all-cause mortality were tracked using hospital records, as were documented incidences of severe hypoglycemia.

Results based on an average follow-up period of a little more than a than a year determined greater dangers for a sulfonylurea switch or addition. Specifically, the study found that switching and/or adding sulfonylureas increased the risk of myocardial infarction incidence rate of 7.8 versus 6.2 per 1,000 person years, all-cause mortality 27.3 versus 21.5, and severe hypoglycemia 5.5 versus 0.7, compared with continuing metformin alone.

A trend toward increased risk of ischemic stroke (6.7 vs. 5.5 per 1,000 person years) and cardiovascular death (9.4 vs. 8.1) were also documented 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 ischemic stroke, cardiovascular death, or severe hypoglycemia,” study authors conclude.

They went on to make an additional recommendation based on the findings that the greater risks tended to be “driven by switching to sulfonylureas and not the addition of sulfonylureas.” The study authors suggest “Thus, in line with current recommendations on the treatment of type 2 diabetes, continuing metformin when introducing sulfonylureas is safer than switching.”

The researchers caution that the study was observational, and, therefore, could not establish cause and effect. But the study was considered strong because of the large sample size.

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