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

Table 3 Hazard ratios in metformin-treated type 2 diabetes for cancer incidence

Cancer type	cancer cases/total	ID^†	Model 1^‡ HR (95%CI)	Model 2^§ HR (95%CI)	Model 3^¶ HR (95%CI)
Total cancer
Comparator^††	140/4327	91.7	ref.	ref.	ref.
Metformin users	199/11390	44.8	0.47 (0.38-0.59)***	0.50 (0.40-0.62)***	0.12 (0.08-0.19)***
Esophagus cancer
Comparator^††	6/4193	4.03	ref.	ref.	ref.
Metformin users	21/11212	4.78	1.15 (0.46-2.84)	1.27 (0.51-3.16)	0.44 (0.07-2.61)
Stomach cancer
Comparator^††	10/4197	6.71	ref.	ref.	ref.
Metformin users	24/11215	5.46	0.78 (0.37-1.63)	0.86 (0.41-1.81)	1.41 (0.42-4.73)
Colorectal cancer
Comparator^††	26/4213	17.4	ref.	ref.	ref.
Metformin users	30/11221	6.83	0.38 (0.23-0.65)***	0.42 (0.25-0.71)**	0.36 (0.13-0.98)*
Liver cancer
Comparator^††	28/4215	18.7	ref.	ref.	ref.
Metformin users	45/11236	10.2	0.53 (0.33-0.85)**	0.54 (0.34-0.87)*	0.06 (0.02-0.16)***
Pancreas cancer
Comparator^††	7/4194	4.70	ref.	ref.	ref.
Metformin users	21/11212	4.78	0.99 (0.42-2.33)	1.11 (0.47-2.62)	0.15 (0.03-0.79)*

†: Incidence density per 10,000 person-years.
‡: Unadjusted hazard ratio, HR, (95% confidence interval, 95% CI), by Cox regression.
§: Adjusted for age group, and gender.
¶: Adjusted for age group, gender, other oral anti-hyperglycemic medication, CCI score, and duration of metformin exposure which was treated as a time dependent variable
††: Diabetes patients who had no metformin, but might have used any other oral anti-hyperglycemic medication.
*P < .05, **P < .01, ***P < .001

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