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Sulfonylureas pose no additional threat for early death, CV events
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BOSTON – Sulfonylureas used to treat type 2 diabetes are generally safe, with no increased risk for adverse cardiovascular events, stroke or early death, according to study findings presented here.
In a systematic review of randomized clinical trials and a direct meta-analysis with trial sequential analysis, researchers found the data was powerful enough to exclude an absolute risk as small as 0.5%.
“An absolute difference of 0.5% between sulfonylureas and other treatments in terms of all-cause mortality, cardiovascular mortality, myocardial infarction and stoke could be firmly discarded,” Dimitris V. Rados, MD, of Clinical Hospital of Porto Alegre, Brazil, told Endocrine Today. “So these drugs are safe, at least in this measurable amount.”
Rados and colleagues analyzed data from 47 randomized controlled trials of at least 52 weeks’ duration evaluating second- or third-generation sulfonylureas, including glyburide, glibenclamide, gliclazide or glipizide, in the treatment of type 2 diabetes. The trials included a total of 37,650 participants (mean age, 57.3 years; mean HbA1c, 7.2%). Researchers used the Peto odds ratio method to summarize the data. Researchers also performed trial sequential analysis to quantify statistical reliability, considering an absolute difference between the arms of 0.5%. Researchers included studies with zero events in both arms.
Sulfonylureas across all comparator classes were not associated with total mortality (OR = 1.12; 95% C.I., 0.96-1.30) or cardiovascular mortality (OR = 1.12; 95% C.I., 0.87-1.42). Researchers also found sulfonylureas were not correlated with an increased risk of myocardial infarction (OR = 0.92; 95% CI, 0.76-1.12) or stroke (OR = 1.16; 95% CI, 0.81-1.66).
In a sub-analysis, glipizide was the only sulfonylurea associated with an increased risk for total and CV mortality, according to researchers, but the harm boundary was not reached. When excluding glipizide from the main analysis, the odds ratio was 1.03 (95% CI, 0.86-1.23). Quality of the evidence was considered high for mortality outcomes and moderate for stroke and myocardial infarction.
The safety of sulfonylureas are in permanent debate, Rados said, pointing to observational studies that identified increased risk for early death and systematic reviews that reported conflicting results, while randomized clinical trials found no risk among second- and third-generation sulfonylureas.
“Although sulfonylureas are not perfect drugs, clinicians can still prescribe them as the currently available data supports their safety,” Rados said after the presentation.
More research is needed involving recent studies to expand on the findings, Rados said.
“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,” Rados said. “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.” – by Regina Schaffer
Reference:
Rados DV, et al. Abstract 16-OR. Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.
D isclosure: Rados reports no relevant financial disclosures. Please see the full study for other authors’ relevant financial disclosures.