Insulin-Lowering Effects of Metformin in Women with Early Breast Cancer

Background: Obesity has been associated with poor breast cancer outcomes. Insulin may mediate this effect, interacting with insulin receptors on breast cancer cells. Metformin, a biguanide derivative used in the treatment of diabetes, reduces insulin levels in subjects with type 2 diabetes and other insulin-resistant states. If metformin lowers insulin levels in women with breast cancer, it may also improve breast cancer outcomes. Patients and Methods: We administered metformin (1500 mg per day) to 32 women with early breast cancer whose baseline insulin levels were at least 45 pmol/L to determine its effect on insulin levels. Results: Twenty-two (69%) women completed the 6-month intervention. Four women (12.5%) dropped out because of gastrointestinal side effects; the others withdrew for reasons not related to toxicity. Completers were similar to noncompleters for all baseline characteristics apart from global health, overall physical condition, overall quality of life, physical function, and social function (HRQOL), which was decreased in noncompleters. Metformin significantly lowered fasting insulin levels by 15.8 pmol/L (22.4%; P = .024) and improved insulin sensitivity by 25.6% (P = .018), total cholesterol by 5.3%, and low-density lipoprotein (LDL) cholesterol by 9.1%. Metformin reduced weight by 1.9 kg (2.5%; P = .01), and it had no significant effects on HRQOL or specific gastrointestinal symptoms (appetite, nausea/vomiting, diarrhea, constipation). Conclusion: Metformin significantly lowers insulin levels, and it improves insulin resistance in nondiabetic women with breast cancer. A phase III randomized trial to evaluate its effects an breast cancer outcomes is recommended.