Table 3.

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

Exposure InformationColorectal cancer–specific survivalOverall survival
Main analysisa(n = 3,816)Person-yearsDeaths (crude rate)cUnivariate HR (95% CI)Adjusted HR (95% CI)Deaths (crude rate)cUnivariate HR (95% CI)Adjusted HR (95% CI)
 Nondiabetic3,50115,9121,082 (68)(Ref)(Ref)1,897 (119)(Ref)(Ref)
 Diabetic - No metformin10836135 (97)1.27 (0.91–1.78)1.22 (0.69–2.14)74 (205)1.54 (1.22–1.95)1.19 (0.82–1.74)
 Any metformin20783358 (70)0.91 (0.70–1.18)0.84 (0.58–1.20)122 (146)1.11 (0.92–1.33)0.90 (0.69–1.17)
Stratified analyses
Dosing intensitya
 Any metformin (low)10340631 (76)0.99 (0.70–1.42)0.87 (0.56–1.37)68 (168)1.26 (0.99–1.61)0.99 (0.72–1.35)
 Any metformin (high)10442727 (63)0.83 (0.56–1.21)0.80 (0.51–1.26)54 (126)0.96 (0.73–1.26)0.82 (0.60–1.13)
Coprescriptionb
 Metformin + co-Rx ADDs12548335 (73)0.93 (0.67–1.31)0.82 (0.58–1.16)76 (157)1.18 (0.94–1.48)1.04 (0.82–1.32)
 Metformin exclusively8235023 (66)0.87 (0.58–1.32)0.73 (0.48–1.11)46 (131)1.01 (0.75–1.35)0.82 (0.61–1.10)
Dosing intensity and coprescriptionb
 Metformin (low) + co-Rx ADDs6525917 (66)0.86 (0.53–1.39)0.74 (0.45–1.20)41 (158)1.20 (0.88–1.63)1.04 (0.76–1.43)
 Metformin (high) + co-Rx ADDs6022318 (81)1.01 (0.64–1.62)0.93 (0.58–1.49)35 (157)1.16 (0.83–1.62)1.04 (0.74–1.45)
 Metformin (low) exclusively3814614 (96)1.22 (0.72–2.07)0.93 (0.55–1.59)27 (185)1.37 (0.94–2.01)1.02 (0.69–1.50)
 Metformin (high) exclusively442049 (44)0.60 (0.31–1.16)0.54 (0.28–1.05)19 (93)0.73 (0.46–1.15)0.64 (0.41–1.01)

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

  • aAdjusted for age, tumor stage, tumor grade, year of diagnosis, comorbidity score, aspirin use, exposure to nonmetformin ADDs (sulfonylureas yes/no, insulin yes/no, and other ADDs yes/no).

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