Table 1

Arguments for and against the modern sulfonylureas

For the prosecutionFor the defenseEvidence yet to be presented
Ischemic preconditioningTolbutamide and glyburide interfere with ischemic preconditioningGliclazide, glipizide, and glimepiride do not alter ischemic preconditioning
HypoglycemiaHypoglycemia and weight gain occur with all sulfonylureasGliclazide, glipizide, and glimepiride cause less hypoglycemia than glyburide
Observational studiesCardiovascular risk is higher with sulfonylureas vs. comparators in some studiesCardiovascular risk is mainly higher vs. metformin, which decreases riskStudies with better design to limit bias
Randomized studiesShort-term mortality was increased with tolbutamide in UGDPLong-term mortality was decreased with glyburide, chlorpropamide, and glipizide in UKPDSCAROLINA (glimepiride vs. linagliptin)
GRADE (glimepiride vs. other second-line agents)
  • The modern sulfonylureas—gliclazide, glipizide, and glimepiride—are accused of “increased risk of cardiovascular mortality.” The table summarizes the main arguments for prosecution and defense, including evidence from studies of older sulfonylureas.