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First-line treatment with sulfonylureas instead of metformin in people with type 2 diabetes is associated with a significantly elevated risk of death, according to results from an observational study presented at the European Association for the Study of Diabetes (EASD) meeting in Barcelona.

Although guidelines do not recommend the use of sulfonylureas for first-line treatment, the drugs are still commonly prescribed this way in many countries. CJ Currie, an epidemiologist at Cardiff University in the UK, said that 7% of diabetics in the UK receive first-line treatment with sulfonylureas. He presented data from the Clinical Practice Research Datalink (CPRD), which includes 10% of primary care patients in the UK. Between 2000 and 2012, 76,811 patients with type 2 diabetes began glucose-lowering treatment with metformin, while 15,687 began treatment with sulfonylureas (which include glipizide, glyburide, and glimepiride).

After adjusting for baseline differences, mortality was 58% higher in the sulfonylurea group. (The crude rates were 44.6 deaths per 1000 patient-years in the sulfonylurea group versus 13.6 in the metformin group.) A significant mortality increase in the sulfonylurea group was found in additional direct-matched and propensity-matched analyses.

The authors acknowledged that while “residual confounding and confounding by indication may remain, this study indicates that treatment with first-line monotherapy with sulfonylureas should be reconsidered.” At a news conference in Barcelona, Currie said that because this is an observational study it is “not a smoking gun,” but he strongly recommended that regulatory authorities take a close look at the issue.

At the press conference Currie also presented data from an analysis of second-line therapy, comparing the combination of metformin and sulfonylureas, in 34,000 patients, with the combination of metformin and DPP-4 inhibitors, or glistens, in 8000 patients. Overall there were 1200 deaths. There were 16.0 deaths per 1000 patient-years in the metformin-sulfonylurea group versus 7.3 for the metformin-DPP-4 group. After adjusting for baseline characteristics Currie said there was a significant 35% increase in death in the metformin-sulfonylurea group.