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Sulfonylurea’s Cardiotoxicity Probed

The risk of ischemic events may be higher with a specific subclass of sulfonylureas…. 

Dr. Scot Simpson (University of Alberta, Edmonton), at the European Association for the Study of Diabetes 2012 Annual Meeting, reported that rates of ACS-related hospitalization or death were higher among patients taking glyburide than those taking gliclazide.

Simpson and colleagues reviewed administrative health records for the province of Alberta, Canada, identifying more than 11,000 diabetic patients using either gliclazide or glyburide who also had a history of ischemic heart disease. Over 1000 person-years, researchers saw 99.6 ACS-related hospitalizations or deaths among patients taking glyburide and 88.9 among patients taking gliclazide as their only sulfonylurea. The difference was small but statistically different (p<0.05), Simpson stressed. ACS-related hospitalizations were also slightly higher among glyburide users (87.7 vs 78.1; p<0.05). ACS-related deaths were not statistically different.

Expressed as an incident-rate ratio, the risk of an ACS-related hospitalization or death was increased 14% and the risk of an ACS-related hospitalization was increased by 16%. This yielded a number needed to harm of 25 for the combined primary end point and 34 for ACS hospitalizations.

"It’s an ongoing debate: are sulfonylureas safe?" Simpson stated that, "Our take on this is, if you look at sulfonylureas vs no sulfonylureas, they probably are worse than other diabetes drugs, like metformin or the GLP-1s, although we don’t have much data yet on these for long-term safety and efficacy. We wanted to ask, if you have to start a sulfonylurea, which is the safer or better one? And what we are showing in this study is that probably using gliclazide is a bit safer than glyburide, but the magnitude of the difference is very, very small."

The clinical impact of this difference, Simpson conceded, is "debatable." He believes the data may have more value from a public-policy standpoint — for example, which drug should be listed on government formularies — but he acknowledged that this study, on its own, won’t carry a lot of weight.

He and his colleagues are working on the theory that the different results for the two sulfonylureas may relate to their different effects on ischemic preconditioning, since, at usual therapeutic doses, glyburide is more likely to inhibit cardiac KATP channels, potentially blunting the heart’s ability to protect against ischemia.

Since a randomized controlled trial comparing the two agents is unlikely, another way to explore this theory would be to look at infarct size, Simpson suggested, or compare other clinical outcomes.

Dr. Nick Wareham (Institute of Metabolic Science, Cambridge, UK), Session moderator, however, expressed caution over the study results, stating that, "These are preliminary data, they’re observational, there are all sorts of potential confounding factors, and I think it’s a bit premature to leap to any conclusions."

In particular, he said that speculation about a differential effect on ischemic preconditioning is a stretch. For example, choice of one sulfonylurea over another might just be a marker for different types of physician prescribing habits, Wareham noted.

Abdelmoneim A, Eurich DT, Gamble JM, et al. Risk of acute coronary syndrome differs with glyburide and gliclazide treatment in patients with type 2 diabetes and ischaemic heart disease: A population-based cohort study. European Association for the Study of Diabetes 2012 Meeting; October 2, 2012; Berlin, Germany.