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Diabetes Obes Metab. 2013 Oct;15(10):938-53. doi: 10.1111/dom.12116. Epub 2013 May 13.

Cardiovascular safety of sulfonylureas: a meta-analysis of randomized clinical trials.

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Geriatric Cardiology, Careggi Teaching Hospital, Florence, Italy.



Cardiovascular safety of sulfonylurea has been questioned by some authors. This article aims at collecting all available data on this issue from randomized trials.


A meta-analysis was performed including all trials with a duration of at least 6 months, comparing a sulfonylurea with a non-sulfonylurea agent in type 2 diabetes. Major cardiovascular events (MACE) and mortality were retrieved and combined to calculate Mantel-Haenzel odds ratio (MH-OR).


Of the 115 selected trials, 62 reported information on MACE, and 30 reported at least one event. MH-OR for sulfonylurea was 1.08 [0.86-1.36], p = 0.52 (1.85 [1.20-2.87], p = 0.005, in the five trials vs. DPP4 inhibitors, no significant differences vs. other comparators). The MH-OR for myocardial infarction and stroke was 0.88 [0.75-1.04], p = 0.13 and 1.28 [1.03-1.60], p = 0.026, respectively. Mortality was significantly increased with sulfonylureas (MH-OR: 1.22 [1.01-1.49], p = 0.047).


In type 2 diabetes, the use of sulfonylureas is associated with increased mortality and a higher risk of stroke, whereas the overall incidence of MACE appears to be unaffected. Significant differences in cardiovascular risk could be present in direct comparisons with specific classes of glucose-lowering agents, such as DPP4 inhibitors, but this hypothesis needs to be confirmed in long-term cardiovascular outcomes trials. The results of this meta-analysis need to be interpreted with caution, mainly because of limitations in trial quality and under-reporting of information on cardiovascular events and mortality. However, the cardiovascular safety of sulfonylureas cannot be considered established unless it is evaluated in long-term cardiovascular outcomes trials.


cardiovascular disease; meta-analysis; sulfonylureas

[Indexed for MEDLINE]

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