Switching to second-line treatment with sulfonylureas was associated with an increased risk for myocardial infarction, all-cause mortality, and severe hypoglycemia in type 2 diabetes compared with remaining on metformin monotherapy, according to a study published in the BMJ.

Sulfonylureas are the most commonly prescribed second-line antidiabetic drugs, and are initiated after treatment failure with metformin. The current population-based study examined whether the use of second-line sulfonylureas is associated with an increased risk for cardiovascular events and death, all-cause mortality, and severe hypoglycemia in patients with type 2 diabetes compared with continuing metformin monotherapy.

The UK Clinical Practice Research Datalink was used to identify 77,138 patients with a first prescription for metformin between April 1, 1998, and March 31, 2013. A total of 25,699 patients added or switched to sulfonylureas during follow-up, with a mean follow up of 1.1 years. Participants who added or switched to sulfonylureas were at an increased risk for myocardial infarction compared with those who used metformin monotherapy (incidence rate, 7.8 vs 6.2 per 1000 person-years; hazard ratio [HR], 1.26; 95% CI, 1.01-1.56), all-cause mortality (incidence rate, 27.3 vs 21.5 per 1000 person-years; HR, 1.28; 95% CI, 1.15-1.44), and severe hypoglycemia (incidence rate, 5.5 vs 0.7 per 1000 person-years; HR, 7.60; 95% CI, 4.64-12.44). A trend was observed toward an increased risk for ischemic stroke (incidence rate, 6.7 vs 5.5 per 1000 person-years; HR, 1.24; 95% CI, 0.99-1.56) and cardiovascular death (incidence rate, 9.4 vs 8.1 per 1000 person-years; HR, 1.18; 95% CI, 0.98-1.43) with adding or switching to sulfonylureas compared with metformin monotherapy.

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Switching to sulfonylureas as compared with adding them to metformin therapy was associated with a greater risk for myocardial infarction (HR, 1.51; 95% CI, 1.03-2.24), as well as all-cause mortality (HR, 1.23; 95% CI, 1.00-1.50).

The investigators concluded that, “in line with current recommendations on the treatment of type 2 diabetes, continuing metformin when introducing sulfonylureas is safer than switching.”

Reference

Douros A, Dell’Aniello S, Yu OHY, Filion KB, Azoulay L, Suissa S. 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.