The Infamous, Famous Sulfonylureas and Cardiovascular Safety: Much Ado About Nothing?

Sulfonylureas (SUs) are one of the most commonly used glucose-lowering agents worldwide. While their efficacy is undisputed, their cardiovascular safety has been debated since the 1970's.

With no dedicated cardiovascular studies to definitively answer this question, observational studies and meta-analyses abound and have reported divergent results, fueling the controversy. Studies that compared SUs to metformin or newer agents, like GLP-1 agonists and SGLT2 inhibitors, suggest a difference in cardiovascular events, yet this is likely the result of beneficial effects of the latter. Studies comparing SUs to other agents have been reassuring. SUs remain a common choice of treatment for patients with type 2 diabetes due to their exceptional value. They are effective at lowering glucose and thus contributing to the prevention of microvascular complications. Weight gain and hypoglycemia are their main side effects, although less severe when compared to insulin treatment. Their cardiovascular safety will remain a controversial topic due to lack of conclusive data, but there is no definitive evidence of harm with the second-generation agents.