Patients taking sulfonylureas as second-line therapy—replacing rather than adding on to metformin—had increased risks for myocardial infarction, all-cause mortality, and severe hypoglycemia compared with those on metformin monotherapy. This was true even when metformin-only patients had suboptimal glycemic control.
This class of drugs is also associated with weight gain, which may contribute to arrhythmias and cardiac ischemia.
Current guidelines downplay the use of sulfonylureas, although they remain the most common second-line agents for type 2 diabetes despite their consistent association with higher cardiovascular risk and the availability of newer classes of medications.
An editorial[1] reminded us that continuing metformin alone and accepting higher A1c targets is preferable to switching to sulfonylureas for both macrovascular outcomes and hypoglycemia.