No reduced risk of overall, colorectal, lung, breast, and prostate cancer with metformin therapy in diabetic patients: database analyses from Germany and the UK

Abstract

Background: In observational studies, a lower cancer risk was reported for patients with diabetes using metformin. However, many of these studies had shortcomings like time-related biases. We aimed to compare the incidence rate of any cancer and some selected cancer sites in metformin, sulfonylurea, and insulin users and to reduce some major biases common in observational studies.

Methods: In a retrospective database study, we used patient data from general practices throughout Germany and the UK. Eighty thousand two hundred and sixty-three patients aged 30-89 years at diagnosis of diabetes were observed for a mean follow-up of 4.8 years after the first antidiabetes medication. In Cox regression models adjusted for age, sex, country, metabolic factors, diabetes duration, medication, and comorbidity, patients who started using metformin were compared with those who started using sulfonylurea (or insulin) (intention-to-treat type analysis), and, additionally, patients with metformin monotherapy were compared with those with sulfonylurea (or insulin) monotherapy. The initial 12 months of follow-up after the first antidiabetes prescription were excluded.

Results: Four thousand seven hundred seventy-nine (6.0%) incident cases of cancer were identified. Throughout all analyses, hazard ratios were close to the null for comparisons of metformin use with sulfonylurea and insulin use. For example, in intention-to-treat analyses comparing metformin with sulfonylurea use, hazard ratios were 1.05 (95%CI: 0.99-1.12) for any cancer, 1.05 (0.85-1.30) for colorectal, 1.04 (0.82-1.31) for lung, 1.03 (0.81-1.30) for breast, and 0.89 (0.73-1.08) for prostate cancer.

Conclusion: This study provides evidence that metformin has no protective effect on the incidence of cancer in persons with diabetes.

Keywords: cancer; diabetes mellitus; insulin; metformin; neoplasms; pharmacoepidemiology; sulfonylurea.