A systematic review and meta-analysis has revealed that sulphonylureas pose no increased risk of cardiovascular (CV) events, stroke or early death in people with type 2 diabetes. The study, which analysed a total of 37 650 people and was powered to exclude an absolute risk as small as 0.5%, was presented at the American Diabetes Association 75th Scientific Sessions in Boston, MA, USA.
The authors of the study analysed data from 47 randomised controlled trials of at least 1 year’s duration evaluating the second- or third-generation sulphonylureas. Pooled data across all comparisons showed that the drugs were not associated with total mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.96–1.30), CV mortality (OR, 1.12; 95% CI, 0.87–1.42) myocardial infarction (OR, 0.92; 95% CI, 0.76–1.12) or stroke (OR, 1.16; 95% CI, 0.81–1.66).
Subanalyses showed that glipizide alone was significantly associated with all-cause and CV mortality; however, the harm boundary was not reached and the authors cautioned against drawing conclusions from the subanalyses given the small number of people and events. Excluding glipizide from the main analysis reduced the OR associated with the other sulphonylureas to 1.03 (95% CI, 0.86–1.23).
Dr Dimitris Rados (Clinical Hospital of Porto Alegre, Brazil), the study author, said: “Although sulfonylureas are not perfect drugs, clinicians can still prescribe them as the currently available data supports their safety.”
The use of sulphonylureas is a matter of debate among clinicians, many of whom are concerned about the associated risks of hypoglycaemia, weight gain and CV disease. These results, obtained from randomised controlled studies only, contrast with those of a previous meta-analysis of cohort and observational studies, with a total of 551 912 participants, which demonstrated an increased risk of total mortality (OR, 1.92) and CV mortality (OR, 2.72).
The debate continues, and even Dr Ramos stopped short of recommending sulphonylureas outright: “As some of our data relied on studies from the 1990s, new randomized trials with the adequate, long-term follow-up could update this topic. Besides this, the finding that sulfonylureas are not associated with increased risk is not good enough, as we should focus on identifying drugs capable of reducing mortality on type 2 diabetic patients.”
The study abstract can be read here.
