Table 1

Methodological limitations of observational studies investigating the effects of sulfonylureas alone or in combination with other antidiabetic drugs on the incidence of cardiovascular events or mortality

AuthorStudy designComparisonOutcome(s)Relative riska (95% CI)
Exposure misclassification
 Evans et al. (17)CohortSulfonylureas vs. metforminAll-cause mortality1.43 (1.15–1.77)
Sulfonylureas vs. metforminCardiovascular mortality1.70 (1.18–2.45)
 Corrao et al. (36)CohortSulfonylureas vs. metforminAll-cause mortality1.37 (1.26–1.49)
 Pantalone et al. (42)CohortGlipizide vs. metforminAll-cause mortality1.64 (1.39–1.94)
Glyburide vs. metforminAll-cause mortality1.59 (1.35–1.88)
Glimepiride vs. metforminAll-cause mortality1.68 (1.37–2.06)
Time-lag bias
 Mannucci et al. (12)CohortSulfonylurea + metformin vs. other antidiabetic drugsAll-cause mortality2.08 (1.18–3.67)b
1.68 (1.01–2.79)c
 Koro et al. (13)Nested case-controlSulfonylureas vs. no treatmentCHF1.19 (1.02–1.39)
 Kahler et al. (20)CohortSulfonylureas vs. metforminAll-cause mortality1.15 (0.91–1.47)d
Sulfonylureas vs. TZDAll-cause mortality1.04 (0.75–1.46)d
 Tzoulaki et al. (25)CohortSulfonylureas vs. metforminAll-cause mortality1.37 (1.11–1.71)e
Sulfonylureas vs. metforminAll-cause mortality1.24 (1.14–1.35)f
 Pantalone et al. (26)CohortSulfonylureas vs. metforminCHF1.32 (1.10–1.56)d
Sulfonylureas vs. metforminAll-cause mortality1.85 (1.56–2.17)d
Sulfonylureas vs. pioglitazoneAll-cause mortality1.69 (1.23–2.33)d
 Horsdal et al. (37)Case-controlSulfonylureas vs. metforminMyocardial infarction1.16 (1.05–1.28)d
Sulfonylureas vs. insulinMyocardial infarction1.09 (1.01–1.16)d
 Pantalone et al. (42)CohortGlipizide vs. metforminAll-cause mortality1.64 (1.39–1.94)
Glyburide vs. metforminAll-cause mortality1.59 (1.35–1.88)
Glimepiride vs. metforminAll-cause mortality1.68 (1.37–2.06)
 Currie et al. (45)CohortSulfonylureas vs. metforminAll-cause mortality1.75 (1.64–1.86)
 Ghotbi et al. (48)CohortSulfonylureas vs. insulinMACEg0.95 (0.73–1.22)
Sulfonylureas vs. insulinAll-cause mortality1.20 (0.90–1.60)
Selection bias
 Johnson et al. (14)CohortSulfonylureas vs. metforminNonfatal hospitalization, all-cause mortality1.23 (1.03–1.47)d
 McAlister et al. (22)CohortSulfonylureas vs. metforminCHF1.24 (1.01–1.54)
  • MACE, major adverse cardiovascular event; TZD, thiazolidinedione.

  • aRelative risk is used as a generic term for rate ratio, HR, and odds ratio.

  • bEstimated among women.

  • cEstimated among men.

  • dFor consistency with the rest of the table, the relative risks and 95% CIs were inversed when sulfonylureas were the comparator group.

  • eAnalysis based on first-generation sulfonylureas.

  • fAnalysis based on second-generation sulfonylureas.

  • gIncluded nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death.