Table 3

Subgroup and sensitivity analyses of the relative risk of bladder cancer in the metformin relative to SU cohorts

DescriptionTotal cancers, nTotal patients, nUnadjusted, HR (95% CI)Fully adjusted, HR (95% CI)*
Original analysis26287,6000.63 (0.47–0.83)0.81 (0.60–1.09)
Subgroup analysis of first-line therapy25082,5700.63 (0.47–0.84)0.81 (0.60–1.09)
Sensitivity analyses
 Use of 1-year baseline period to define new user25284,0310.66 (0.49–0.88)0.84 (0.61–1.14)
 Receipt of two prescriptions in 3 months to define exposure26287,2770.64 (0.48–0.85)0.81 (0.60–1.09)
 Exclusion of bladder cancers during first year of follow-up18587,6000.69 (0.49–0.97)0.87 (0.60–1.25)
 Multiple imputation of BMI and HbA1c level26287,6000.64 (0.48–0.85)0.84 (0.62–1.12)
 Use of mean BMI during follow-up26287,6000.63 (0.47–0.83)0.90 (0.67–1.22)
 Use of mean HbA1c level during follow-up26287,6000.63 (0.47–0.83)0.82 (0.61–1.11)
 Use of insulin and TZDs as time-updating variables26287,6000.63 (0.47–0.83)0.86 (0.64–1.15)
 Adjustment for diabetes duration26287,6000.63 (0.47–0.83)0.81 (0.60–1.10)
 Adjustment for prior use of other diabetes medications26287,6000.63 (0.47–0.83)0.81 (0.60–1.10)
 Initial treatment carried forward§38587,6000.78 (0.62–0.98)0.89 (0.70–1.13)
  • *Adjusted for age (<60, 60–69, and 70 years), sex, smoking (ever vs. never), HbA1c level (<7%, 7–7.9%, 8–8.9%, and 9%), and obesity (BMI 30 kg/m2).

  • †Exclusion of subjects with use of diabetes therapies (n = 5,030; 5.7%) prior to start of follow-up.

  • ‡Linear regression was used to impute missing data on HbA1c levels and BMI. To account for the variability between imputations, SEs were adjusted according to the method proposed by Rubin (30).

  • §Follow-up time continued for metformin or SU users who switched therapy or started combination therapy.