Mortality rates may differ among sulfonylureas, meta-analysis finds

Among sulfonylureas, gliclazide and glimepiride were associated with a lower risk of all-cause and cardiovascular-related mortality than glyburide (known as glibenclamide in some other countries), a meta-analysis found.

Researchers reviewed 24 studies (7 randomized, 17 observational) that reported the risk of all-cause mortality, cardiovascular-related mortality, or myocardial infarction for at least 2 sulfonylureas. They were able to combine mortality data from 23 of the studies, totaling 172,349 patients who used a sulfonylurea, with 18 studies (167,327 patients) in the main analyses of all-cause mortality. Results appeared early online Oct. 23 at The Lancet Diabetes & Endocrinology.

Gliclazide was associated with a significantly lower risk of all-cause and cardiovascular-related mortality compared with glyburide, and glimepiride was associated with a lower risk of all-cause mortality than glyburide. Glipizide was associated with a similar risk of all-cause and cardiovascular-related mortality as glyburide. Overall, 14,970 (9%) of patients died: 841 (4%) of 19,334 gliclazide users, 5,482 (11%) of 49,389 glimepiride users, 2,106 (15%) of 14,464 glipizide users, 5,296 (7%) of 77,169 glyburide users, 1,066 (17%) of 6,187 tolbutamide users, and 179 (23%) of 784 chlorpropamide users.

The relative risk of death compared with glyburide was 0.65 (95% credible interval, 0.53 to 0.79) for gliclazide, 0.83 (95% credible interval, 0.68 to 1.00) for glimepiride, 0.98 (95% credible interval, 0.80 to 1.19) for glipizide, 1.13 (95% credible interval, 0.90 to 1.42) for tolbutamide, and 1.34 (95% credible interval, 0.98 to 1.86) for chlorpropamide.

Similar associations were noted for cardiovascular-related mortality. The relative risk compared with glyburide was 0.60 (95% credible interval, 0.45 to 0.84) for gliclazide, 0.79 (95% credible interval, 0.57 to 1.11) for glimepiride, 1.01 (95% credible interval, 0.72 to 1.43) for glipizide, 1.11 (95% credible interval, 0.79 to 1.55) for tolbutamide, and 1.45 (95% credible interval, 0.88 to 2.44) for chlorpropamide. There were no significant differences in risk of myocardial infarction among the sulfonylureas. The authors concluded by recommending clinicians should consider possible differences in risk of mortality when selecting a sulfonylurea and caution that this hypothesis needs to be tested in a randomized clinical trial.

An editorial noted that sulfonylureas have historically been analyzed as a drug class, despite their “vast differences” in pharmacological properties, concluding that “continuing to prescribe [glyburide] seems inappropriate in view of its higher risk of hypoglycemia and ability to abolish ischemic preconditioning, even if the jury is still out regarding whether or not it is associated with a higher risk of adverse cardiovascular outcomes or mortality versus other sulfonylureas.”