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Diabetes Drug Intrigues Investigators

Network - Fall 2008

Metformin, the common first-line drug for type 2 diabetes, may be effective in increasing pathologic complete response rates in diabetic women with early stage breast cancer who took the drug during chemotherapy prior to having surgery.

This discovery could pave the way for further research of the drug as a potential cancer therapy, according to researchers at M. D. Anderson.

The retrospective study is the first clinical research observation of the diabetes drug as a potential anti-tumor agent. The findings were presented in a poster discussion session at the annual meeting of the American Society of Clinical Oncology by Sao Jiralerspong, M.D., Ph.D., a fellow, and Ana M. Gonzalez-Angulo, M.D., assistant professor, both in M. D. Anderson’s Department of Breast Medical Oncology.

More than 35 million prescriptions of metformin, an oral medication, are filled annually, according to Gonzalez-Angulo. It’s most often given to diabetic patients who are obese or have insulin resistance.

An independent predictor

The authors decided to conduct the research after a large, intriguing epidemiologic study published last year showed that patients with diabetes who took metformin had lower incidences of cancer as well as better outcomes.

“Metformin has a novel mechanism of action. There have been a number of papers published recently that describe its action through activation of the AMP kinase pathway, which is a cellular energy sensor of the cells and a potentially important pathway for the development of cancer,” Jiralerspong says.

“The other interesting aspect is that metformin works by decreasing the amount of insulin resistance in diabetics, and insulin seems to be a growth factor for cancer,” Gonzalez-Angulo says.

Using the M. D. Anderson Breast Medical Oncology database, Gonzalez-Angulo, Jiralerspong and their team identified 2,529 women with early-stage breast cancer who received chemotherapy in the neoadjuvant, pre-surgery setting. Of the patients, 2,374 were non-diabetic, 68 were diabetic but not taking metaformin and 87 were diabetic and taking the drug. The study’s endpoint was pathologic complete response or the absence of cancer at the time of surgery.

The researchers found that the pathologic complete response rates in the diabetic breast cancer patients taking metformin was 24%, three times higher than the rate of 8% in diabetic patients not taking the drug. In the non-diabetic women, the pathologic complete response rate was 16%. After adjusting for other factors, the researchers found that metformin was an independent predictor of pathologic complete response in diabetic patients.

Understanding why it works

While very exciting, the findings are still very early, Jiralerspong and Gonzalez-Angulo caution, and further investigation with metformin is needed.

“We need to study the mechanism of the drug — perhaps it’s the decrease in insulin levels, or it may be that the drug has an anti-tumor effect that we need to look at in vivo,” Gonzalez-Angulo says. “Our next step is to conduct a number of correlative studies to try and further understand its mechanism.”

M. D. Anderson also plans to open a clinical trial with metformin in combination with hormonal therapy for metastatic breast cancer patients who are obese.

© 2015 The University of Texas MD Anderson Cancer Center