Clinicians should bear in mind the varied mortality rates between sulfonylurea (SU) drugs, which are lower with gliclazide and glimepiride than with glibenclamide, when prescribing these drugs for diabetes, write the authors of a meta-analysis published in The Lancet Diabetes & Endocrinology
on 23 October 2014.
SUs differ with regard to tissue selectivity and risk of hypoglycaemia, and there is ongoing debate about their cardiovascular safety. To assess potential differences, Scot Simpson, from the University of Alberta, Edmonton, Canada, and co-authors searched literature for controlled studies reporting risks of all-cause mortality, cardiovascular mortality or myocardial infarction for at least two SUs.
Their final analysis included 18 studies involving 167,327 patients of whom 14,970 (9%) died. Using standard meta-analysis of direct evidence, gliclazide had the lowest risk of mortality, followed by glimepiride, glipizide, glibenclamide, tolbutamide and chlorpropamide. But when using network meta-analysis, which incorporates both direct and indirect evidence, gliclazide and glimepiride were associated with a significantly lower risk of mortality compared with glibenclamide, whereas glipizide had a similar risk.
Compared with glibenclamide, the relative risk of death was 0.65 for gliclazide, 0.83 for glimepiride, 0.98 for glipizide, 1.13 for tolbutamide, and 1.34 for chlorpropamide. Similar associations were noted for cardiovascular-related mortality, whereas there were no differences in risk of myocardial infarction among the various SUs.
“Findings from this study should be considered hypothesis-generating and need to be verified in a properly designed randomised clinical trial,” the authors conclude, adding that results from ongoing studies (TOSCA IT and CAROLINA) will provide further insights about the use of SUs in diabetes management.
 Simpson SH, Lee J, Choi S et al. Mortality risk among sulfonylureas: a systematic review and network meta-analysis. The Lancet Diabetes & Endocrinology 2014. doi:10.1016/S2213-8587(14)70213-X (accessed 23 October 2014).