We tested this hypothesis using record linkage databases developed in Tayside, Scotland: a diabetes clinical information system (DARTS) and a database of dispensed prescriptions (MEMO).4
We did a pilot case-control study using previously validated methods.5
From 314 127 people who were resident (or died) in Tayside in 1993-2001, 11 876 had been newly diagnosed with type 2 diabetes. Of these, 923 were subsequently admitted to hospital with an ICD-9 or ICD-10 (international classification of diseases, 9th or 10th revision) diagnostic code for malignant cancer in study period (for which first admission occurred at least one year after diagnosis of diabetes). The index date of these cases was the date of first admission. We generated random controls from the diabetic population (two for each case); patients without cancer matched for age, year of diagnosis, and sex, and we gave them matching index dates.
What this paper suggests
Metformin may reduce the risk of cancer in patients with type 2 diabetes
What research is needed now
A more rigorous cohort study, before experimental work is initiated
We collated information about use of metformin for all cases and controls and calculated unadjusted odds ratios using conditional logistic regression (taking matching into account). The proportions of cases and controls for whom confounding data were available were smoking 73%, body mass index 62%, blood pressure 67%, and postcode rank for material deprivation 99%. We categorised continuous variables into quartile groups, with missing values forming a separate category. We adjusted odds ratios for these possible confounders.
More than half of the patients with cancer (488; 53%) were men. Mean age was 73 (standard deviation 9.8) years and mean duration of diabetes was 8.5 (6.4) years. More than a third (336; 36.4%) of the cases had been given at least one prescription for metformin in the year before their index date compared with 732 (39.7%) of the controls. The unadjusted odds ratio was 0.86 (95% confidence interval 0.73 to 1.02). The unadjusted odds ratio for any exposure to metformin since 1993 was 0.79 (0.67 to 0.93).
We also investigated total duration of exposure (time between first and last metformin prescription), total number of prescriptions, and total amount of metformin dispensed since January 1993 (). Adjustment did not greatly affect the risk estimates, indicating no substantial confounding effects.
Metformin use in patients with type 2 diabetes and controls in Tayside, Scotland, 1993-2001