Table 3.

Estimates of lung cancer risk associated with metformin use, by smoking status

Never smokerFormer smokerCurrent smoker
Metformin useNumber of eventsPerson-yearsAdjusteda HR (95% CI)Number of eventsPerson-yearsAdjusteda HR (95% CI)Number of eventsPerson-yearsAdjusteda HR (95% CI)Pinteractionb
Never51103,651.051.00 (reference)22284,763.541.00 (reference)11221,977.451.00 (reference)
Ever2973,907.550.57 (0.33–0.99)11454,161.750.93 (0.71–1.23)9115,298.801.25 (0.88–1.77)0.11
 Total duration, y
  <2.01025,648.960.66 (0.32–1.33)3819,466.590.88 (0.61–1.27)355,792.321.38 (0.91–2.09)
  2.0–4.9924,315.930.56 (0.26–1.20)4117,936.271.00 (0.69–1.45)245,037.570.96 (0.58–1.57)
  ≥5.01023,942.660.48 (0.21–1.09)3516,758.890.93 (0.61–1.44)324,468.911.45 (0.87–2.43)0.35
 Recency of use
  Former914,007.310.79 (0.35–1.80)2911,092.111.00 (0.64–1.56)213,083.621.15 (0.66–2.00)
  Recent79,251.231.10 (0.47–2.56)166,584.151.05 (0.62–1.78)122,054.411.30 (0.69–2.46)
  Current
   <5.0 years632,290.550.34 (0.14–0.81)4423,924.570.87 (0.61–1.23)366,833.891.24 (0.82–1.89)
   ≥5.0 years718,358.460.54 (0.22–1.35)2512,560.920.93 (0.58–1.50)223,326.871.39 (0.79–2.44)0.35
 Cumulative dose (mg), quartiles
  ≤750,000823,566.030.56 (0.26–1.22)3717,291.580.92 (0.64–1.32)315,194.281.34 (0.87–2.06)
  750,001–2,300,0001022,464.730.67 (0.32–1.39)3516,423.180.93 (0.63–1.37)224,567.760.99 (0.60–1.64)
  2,300,001–4,930,000517,918.090.38 (0.14–1.03)2313,135.990.82 (0.51–1.32)263,596.581.50 (0.90–2.50)
  >4,930,00069,958.710.72 (0.26–2.00)197,311.011.26 (0.72–2.20)121,940.181.35 (0.66–2.75)0.46
  • aStratified on age and adjusted for gender, race/ethnicity, birth year, diabetes duration, BMI, alcohol use, Charlson comorbidity index, pack-year history (for former and current smokers), education, income level, creatinine level, HbA1c level, and use of other diabetes medications.

  • bOn the basis of test for interaction between metformin use and smoking status (never, former, and current) on lung cancer risk.