Metformin and biomarkers relevant to neoplasia in nondiabetic patients.

e14615 Background: Use of the anti-diabetic drug Metformin has been associated with reduced risk or improved prognosis of several cancers in both lab models and retrospective population studies of diabetics. Plausible mechanisms of action include (1) reduction in serum levels of insulin or inflammatory cytokines and (2) direct effects on target cells due to action of the drug as an inhibitor of mitochondrial respiration, including activation of AMPK. Methods: Non-diabetic subjects (n = 47) consented to bloodwork and sigmoid biopsy at screening colonoscopy, metformin administration (500 mg TID) for 10 weeks, and end-of-study sigmoid biopsy and bloodwork. Serum assays were performed on both fasting and post standard oral glucose load specimens. Metformin levels were measured by mass spectroscopy. Anti-phospho-histone-3 immunostaining was used to quantify proliferation. Results: Metformin reduced fasting levels of c-peptide, insulin, and IL-6 levels by < 10%, a magnitude of change that laboratory studies sug...