Table 4.

Site-specific HRs of GI cancer in current metformin users compared with current other NIAD users (new-user design)

Cancer siteEsophagus (N = 43)Stomach (N = 53)Liver (N = 15)Biliary tract (N = 20)Pancreas (N = 127)Colorectum (N = 352)
Exposure categoryNHRa (95% CI)NHRa (95% CI)NHRa (95% CI)NHRa (95% CI)NHRa (95% CI)NHRa (95% CI)
Current other NIADsb6Ref.10Ref.<5Ref.<5Ref.23Ref.75Ref.
Current metformin291.59 (0.61–4.14)280.90 (0.41–1.97)111.44 (0.29–7.27)91.12 (0.32–3.94)791.14 (0.68–1.91)2010.78 (0.58–1.05)
Stratified by treatment stagec
 Metformin only202.07 (0.79–5.40)150.79 (0.33–1.88)71.93 (0.38–9.84)61.34 (0.36–5.00)350.71 (0.40–1.26)1210.75 (0.54–1.03)
 Metformin + SU92.18 (0.75–6.31)111.15 (0.47–2.84)<52.37 (0.42–13.45)<51.54 (0.33–7.09)261.98* (1.10–3.59)650.84 (0.59–1.19)
 Metformin + other NIADs0<51.11 (0.14–8.95)00<52.74 (0.92–8.18)60.77 (0.33–1.80)
 Metformin + insulin0<50.66 (0.08–5.47)001410.26* (4.96–21.22)90.72 (0.35–1.48)
Stratified by cumulative dosed
 Low91.35 (0.46–3.96)131.29 (0.53–3.13)<50.80 (0.11–6.01)<51.20 (0.29–4.98)461.23 (0.71–2.13)670.77 (0.54–1.10)
 Medium71.16 (0.36–3.72)50.44 (0.15–1.35)<51.60 (0.26–9.71)<51.32 (0.31–5.70)190.88 (0.46–1.71)670.72 (0.50–1.02)
 High133.32* (1.10–10.06)100.99 (0.36–2.72)52.75 (0.43–17.53)<50.53 (0.05–5.24)141.34 (0.60–2.96)670.89 (0.61–1.31)
Past metformin71.46 (0.46–4.65)131.23 (0.50–3.01)<50.43 (0.04–5.12)72.32 (0.63–8.60)240.94 (0.50–1.77)650.79 (0.55–1.13)
Past other NIADs<50.64 (0.08–5.36)<50.57 (0.12–2.63)<51.42 (0.13–15.83)0<50.12* (0.02–0.90)110.41* (0.22–0.78)
  • aAdjusted for age, sex, use of statins (esophageal cancer, gastric cancer, biliary tract cancer, pancreatic cancer), proton pump inhibitors (esophageal cancer, gastric cancer), aspirin (gastric cancer, pancreatic cancer), antihypertensives (esophageal cancer, pancreatic cancer), helicobacter pylori eradication therapy (gastric cancer), insulin (esophageal cancer, gastric cancer, pancreatic cancer, colorectal cancer), history of hospitalization (esophageal cancer, gastric cancer, liver cancer, biliary tract cancer, pancreatic cancer, colorectal cancer), duration of diabetes (gastric cancer, pancreatic cancer, colorectal cancer), and year of start of follow-up (gastric cancer, pancreatic cancer, colorectal cancer).

  • bExcluding metformin.

  • cNot adjusted for insulin use.

  • dLow: <405 g; Medium: 405–999 g; High: ≥999 g.

  • *Statistically significant with P < 0.05.