Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals.
BACKGROUND
Metformin protection against cancer risk in Orientals is uncertain. We examined the possible metformin effect on total, esophageal, gastric, colorectal (CRC), hepatocellular (HCC) and pancreatic cancers in a Taiwanese cohort.


METHODS
A representative sample of 800,000 was drawn from the Taiwanese National Health Insurance data of 2000. A cohort of 480,984 participants 20 years or older, diabetes-cancer-free on 1st January 2000 was formed and categorized as four groups by DM and metformin usage status. Eligible incident cancer events had to occur one year after the index date until the end of 2007. The Cox proportional-hazards model evaluated relative risk of cancer for treated DM patients with or without metformin. The covariates included age, gender, other oral anti-hyperglycemic medication, Charlson comorbidity index (CCI) score and metformin exposure dosage and duration.


RESULTS
With diabetes but no anti-hyperglycemic medication, cancer incidence density increased at least 2-fold for total, CRC and HCC. On metformin, total, CRC and HCC incidences decreased to near non-diabetic levels but to varying degrees depending on gender and cancer type (CRC in women, liver in men). Adjustment for other oral anti-hyperglycemic agents usage and CCI made the benefit of metformin more evident [hazard ratios (95% confidence intervals): total 0.12 (0.08-0.19), CRC 0.36 (0.13-0.98), liver 0.06 (0.02-0.16), pancreas 0.15 (0.03-0.79)]. There was a significant gender interaction with metformin in CRC which favored women. Metformin dosage for a significant decrease in cancer incidence was ≤ 500 mg/day.


CONCLUSIONS
Metformin can reduce the incidences of several gastroenterological cancers in treated diabetes.
School of Public Health, National Defense Medical Center, Taipei, ROC. mmsl@ndmctsgh.edu.tw
Meei-Shyuan
MS
Lee
Chih-Cheng
CC
Hsu
Mark L
ML
Wahlqvist
Hsin-Ni
HN
Tsai
Yu-Hung
YH
Chang
Yi-Chen
YC
Huang
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries / Q000706:statistics & numerical data; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
D007004:Hypoglycemic Agents; D008687:Metformin
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