Table 2.

Univariate and multivariate HRs for metformin exposure and mortality; diabetic subgroup, stages I–III colorectal cancer

Exposure InformationColorectal cancer–specific survivalOverall survival
Main analysisa(n = 315)Person-yearsDeaths (crude rate)cUnivariate HR (95% CI)Adjusted HR (95% CI)Deaths (crude rate)cUnivariate HR (95% CI)Adjusted HR (95% CI)
 No metformin10836135 (97)(Ref)(Ref)74 (205)(Ref)(Ref)
 Any metformin20783358 (70)0.72 (0.48–1.10)0.61 (0.37–1.01)122 (146)0.73 (0.55–0.97)0.69 (0.49–0.97)
Stratified analyses
Dosing intensitya
 Any metformin (low)10340631 (76)0.79 (0.49–1.28)0.62 (0.35–1.10)68 (168)0.83 (0.59–1.15)0.76 (0.52–1.10)
 Any metformin (high)10442727 (63)0.66 (0.40–1.09)0.60 (0.33–1.07)54 (126)0.64 (0.45–0.90)0.62 (0.42–0.93)
Co-prescriptionb
 Metformin + co-Rx ADDs12548335 (73)0.75 (0.47–1.19)0.70 (0.43–1.15)76 (157)0.78 (0.57–1.07)0.77 (0.55–1.08)
 Metformin exclusively8235023 (66)0.69 (0.41–1.17)0.61 (0.35–1.06)46 (131)0.66 (0.46–0.96)0.56 (0.38–0.82)
Dosing intensity and coprescriptionb
 Metformin (low) + Co-Rx ADDs6525917 (66)0.68 (0.38–0.22)0.60 (0.32–1.10)41 (158)0.78 (0.53–1.14)0.74 (0.49–1.12)
 Metformin (high) + co-Rx ADDs6022318 (81)0.81 (0.46–1.44)0.82 (0.45–1.49)35 (157)0.78 (0.52–1.17)0.79 (0.52–1.19)
 Metformin (low) exclusively3814614 (96)0.97 (0.52–1.80)0.81 (0.41–1.58)27 (185)0.91 (0.59–1.42)0.74 (0.46–1.20)
 Metformin (high) exclusively442049 (44)0.48 (0.23–1.00)0.44 (0.20–0.95)19 (93)0.48 (0.29–0.79)0.41 (0.24–0.70)
  • aAdjusted for age, tumor stage, tumor grade, year of diagnosis, comorbidity score, aspirin use, exposure to nonmetformin ADDs (sulfonylureas yes/no, insulin yes/no, other ADDs yes/no), socioeconomic status, and radiation therapy.

  • bAdjusted for age, tumor stage, tumor grade, year of diagnosis, comorbidity score, aspirin use, socioeconomic status, radiation therapy. ‘Co-Rx’ ADDs include sulfonylureas, insulin, and/or other ADDs.

  • cRate calculated as deaths per 1,000 person-years.