medwireNews: Research shows that starting second-line sulfonylurea treatment is associated with an increased risk for cardiovascular and hypoglycemic events among patients with type 2 diabetes in clinical practice, although the risk is less if they continue using metformin rather than switching completely.
As reported in The BMJ, Samy Suissa (Jewish General Hospital, Montréal, Québec, Canada) and colleagues used the UK Clinical Practice Research Datalink to identify 77,138 patients who started on metformin between 1998 and 2013, of whom 25,699 later added or switched to a sulfonylurea.
For each outcome studied, around 23,500 sulfonylurea users were matched to an equal number of patients who remained on metformin monotherapy. Event rates for the outcomes ranged from 3.1 per 1000 patient–years for severe hypoglycemic events to 24.4 per 1000 patient–years for death from any cause.
After accounting for age, sex, and propensity to receive a sulfonylurea, patients who did so had a significant 7.60-fold increase in the risk for severe hypoglycemia compared with those who remained on metformin monotherapy.
They also had significantly increased risks for myocardial infarction and all-cause mortality, by 26% and 28%, respectively, as well as nonsignificant 18% and 24% increases in the risk for cardiovascular death and ischemic stroke.
However, the researchers found this risk to be driven by patients switching to sulfonylureas, as opposed to adding them to metformin. Those who switched had higher rates of all outcomes compared with those who added a sulfonylurea to metformin, with the difference being significant for myocardial infarction and borderline significant for all-cause mortality after accounting for confounders.
In a linked editorial, Lucy D’Agostino McGowan (Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA) and Christianne Roumie (Vanderbilt University Medical Center, Nashville, Tennessee, USA) say that the study addresses “an important clinical question.”
And they note that these risk differences between patients who added and switched to sulfonylureas “could be driven by the possibility that higher doses of sulfonylureas are needed by those who switched.”
The editorialists stress that “[i]t is hard to define clinical practice based on an observational study, as patients using different treatments may differ in ways that are unmeasured,” but nevertheless say the findings probably indicate that “adding a sulfonylurea to metformin treatment is preferable to switching to sulfonylurea monotherapy.”
They add: “It also suggests that continuing metformin alone and accepting higher [glycated hemoglobin] targets is preferable to switching to sulfonylureas when considering both macrovascular outcomes and hypoglycaemia.”
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