Table 2.

Risk estimates for metformin and cancer risk

Source (Country)Treatment comparisonRisk estimates and 95%CIAdjusting variables (other than age & sex)
Yang et al., 2004 (UK) (40)3+ years of metformin users vs. not usersColon: 1.0 (0.6-1.7)*Smoking, history of cholecystectomy, diabetes duration, BMI, insulin use, sulphonylurea use, aspirin/NSAID use
combination metformin + sulphonylureas Colon: 1.2 (0.7-2.2)
Bowker et al., 2006 (Canada) (41)sulphonylureas and exogenous insulin usersFor any site: 0.77 (0.63-0.91)*Insulin use, comorbidity
Monami et al., 2008 (Italy) (43)other hypoglycaemic drugs usersFor any site and
  • –at any time: 0.6 (P > 0.05)

  • –at least 12 months: 0.33 (P < 0.001)

  • –at least 36 months: 0.28 (0.13-0.57)*

Smoking, alcohol use, comorbidity, BMI, HbA1c, diabetes duration, concomitant hypoglycemic treatment
Libby et al., 2009 (Scotland, UK) (36)non metformin usersOverall cancer: 0.63 (0.53-0.75)*Smoking, BMI, HbA1c, material deprivation, other drug use (sulphonylureas or insulin)
Bowel cancer: 0.6 (0.38-0.94); Lung cancer: 0.7 (0.43-1.15); Breast cancer: 0.6 (0.32-1.10)
Cancer incidence by maximum dose, ≥4 y. of f-up: Low, 0.16 (0.06-0.44); Medium, 0.4 (0.27-0.60); High, 0.15 (0.09-0.25).
Cancer mortality: 0.63 (0.49-0.81)*
Currie et al., 2009 (UK) (44)metformin monotherapy vs. sulfonylureas monotherapyAll solid tumors: 0.74 (0.65-0.84)*Smoking, comorbidity, HbA1c, diabetes duration, weight
For breast: 1.02 (0.71-1.45); For colon: 0.56 (0.40-0.76)
For pancreatic: 0.20 (0.11-0.36); For prostate: 0.93 (0.67-1.32)
metformin monotherapy vs. insulin-based treatmentAll solid tumors: 0.70 (0.63-0.79)
For breast: 0.93 (0.69-1.27); For colon: 0.59 (0.43-0.81)
For pancreatic: 0.22 (0.12-0.38); For prostate: 0.91 (0.66-1.27)
Donadon et al., 2009 (Italy) (34)insulin or sulphonylureas usersMetformin use for hepatocellular cancer among diabetic patients: 0.33 (0.1-0.7)no adjusting variables were considered
Landman et al., 2009 (Netherlands) (42)non metformin usersOverall cancer mortality: 0.43 (0.23-0.80)*;
  • –for every one gram increase in the metformin dosage: 0.58 (0.36-0.93).

Smoking, diabetes duration, HbA1c, serum creatinine, BMI, blood pressure, total cholesterol/HDL, albuminuria, insulin use,sulphonylurea use and macrovascular complications
Wright et al., 2009 (USA, WA) (39)non metformin usersMetformin use for prostate cancer:
  • –among Caucasians 0.56 (0.32-1.00)*

  • –among African-Americans 1.62 (0.53-5.02)

  • –diabetes vs no diabetes: 0.66 (0.39-1.11)

BMI, statin and aspirin use, other diabetes treatment, PSA screening history, family history of PCa
Li et al., 2009 (USA, TX) (38)non metformin usersMetformin use for pancreatic cancer:
  • –all subjects: 0.38 (0.21-0.67)*

  • –among diabetic patients only: 0.38 (0.22-0.69).

  • –never users of insulin: 0.44 (0.22-0.87).

  • –duration of diabetes >2 years: 0.41 (0.19-0.87).

Smoking, alcohol use, BMI, duration of diabetes, insulin use, family history of cancer, race
Hassan et al., 2010 (USA, TX) (45)non metformin usersMetformin use for hepatocellular cancer among diabetic patients: 0.3 (0.2-0.6)Race, educational level, cigarette smoking, alcohol drinking, hepatitis C virus, hepatitis B virus, family history of cancer
Bodmer et al., 2010 (UK) (46)non metformin usersLong metformin use (40+prescriptions) for breast cancer among diabetic patients: 0.44 (0.24-0.82)General practice and calendar time by matching, other use of prandial glucose regulators, acarbose, estrogens, smoking, BMI, diabetes duration and HbA1c
  • *Estimates included in the meta-analysis (when more than one estimates were considered).

  • The authors presented also the estimates for shorter follow-up.