Adding Sulfonylureas to Metformin Can Be Dangerous

When a patient with Type 2 diabetes is not meeting glucose targets on metformin, what is to be done? Some practitioners add a sulfonylurea or switch the patient to sulfonylurea monotherapy, but research indicates that adding or switching to this class of medicines increases the risk of death and cardiovascular events.

An analysis published in The BMJ1 studied roughly 25,000 British patients above the age of 40 on metformin therapy who had added or switched to sulfonylureas. Each was matched with a patient with similar HbA1c and metformin history who had not been given sulfonylureas.

After an average 1.1 years follow-up, sulfonylureas were associated with an increased risk of myocardial infarction, all-cause mortality and severe hypoglycemia compared with continuing metformin monotherapy. There was a trend towards increased risks of stroke and cardiovascular death that did not reach statistical significance.

Adding sulfonylureas was safer than switching to them. The study reports, “Compared with adding sulfonylureas, switching to sulfonylureas was associated with an increased risk of myocardial infarction and all-cause mortality. No differences were observed for ischemic stroke, cardiovascular death or severe hypoglycemia.”

However, a meta-analysis in Diabetes Care in 2008 found that combination therapy had worse outcomes than either metformin or a sulfonylurea used alone, and also worse than no drug therapy at all.2

Other second-line therapies are available. Doctors writing in The Journal of Family Practice recommended using a DPP-4 inhibitor as a second drug, and others are prescribing SGLT2 inhibitors, categories with much lower risk of hypoglycemia. But these drugs are considerably more expensive than sulfonylureas or metformin and may have risks of their own.

A less costly and safer option might be increasing self-management support. Given guidance and support, patients might be able to improve their health without the possible side effects of medications.

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About our experts: David Spero, BSN, RN, Registered Nurse

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