Metformin and other biguanides in oncology: advancing the research agenda.

Retrospective studies that may be impractical to confirm prospectively suggest that diabetics treated with metformin have a substantially reduced cancer burden compared with other diabetics. It is unclear if this reflects a chemopreventive effect, an effect on transformed cells, or both. It also remains to be established if these data have relevance to people without diabetes. Laboratory models, however, provide independent impressive evidence for the activity of metformin and other biguanides in both cancer treatment and chemoprevention. Investigations of mechanisms of action of biguanides have revealed considerable complexity and have identified important gaps in knowledge that should be addressed to ensure the optimal design of clinical trials of these agents. Such trials may define important new indications for biguanides in the prevention and/or treatment of many common cancers.