METFORMIN MAY IMPROVE PANCREATIC CANCER SURVIVAL

NEW YORK (Reuters Health) - Patients with type 2 diabetes who are already taking metformin when they're diagnosed with pancreatic ductal adenocarcinoma (PDAC) may survive longer than those on other medications, according to a new study.

As co-author Dr. Paolo Boffetta told Reuters Health, "Patients who have been treated for diabetes with metformin and who have PDAC appear to have increased survival from this terrible cancer."

"Metformin, which is commonly used to treat diabetes, has been shown to possibly be protective against various cancers," added Dr. Boffetta of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai in New York City. "Given that there is an association between diabetes and pancreatic cancer, controlling diabetes through metformin may also have a positive impact on pancreatic cancer. Although survival remains very bad, it seems to be better."

"If these results hold true and are confirmed in a prospective study, metformin may be considered as the main drug treatment or as an adjuvant drug, not just for diabetes, but also for cancer," Dr. Boffetta added.

As reported online July 19 in the American Journal of Gastroenterology, Dr. Boffetta and his colleagues used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify more than 1,900 patients who were at least 65 years of age when diagnosed with PDAC and pre-existing diabetes mellitus over a five-year period.

All patients had been on hypoglycemic medications for at least one year before their cancer diagnosis; 57.3% were treated with metformin and the remainder received other diabetes medications.

The mean survival for patients taking metformin was 5.5 months compared to 4.2 months for those not on metformin (p<0 .01="" p="">

Patients taking metformin still had significantly lower mortality after adjusting for confounders, including diabetic comorbidity severity index, Charlson score, and chronic kidney disease (hazard ratio, 0.88; p<0 .01="" all="" also="" analysis="" charlson="" dcsi="" disease="" finding="" for="" held="" hypoglycemic="" in="" insulin="" kidney="" medications="" of="" or="" other="" p="" presence="" regardless="" score="" stratified="" the="" true="" use="">

Dr. Animesh Dhar, associate professor of cancer biology at the University of Kansas Medical Center in Kansas City, said in an email, "It is important for clinicians to understand diabetes as a risk factor for PDAC and that metformin could be given as a preventive medicine. It is well established that about 80% of pancreatic cancer patients have glucose intolerance, which can project as one of the risk factors triggering PDAC."

"The mechanism related to PDAC and diabetes is not clear. Therefore, more mechanistic study by basic scientists to understand the role of diabetes and glucose intolerance in PDAC is needed," said Dr. Dhar, who was not involved in the study.

Dr. Edward J. Kim of the University of California, Davis, Comprehensive Cancer Center in Sacramento, said, "A strength of this study is the use of propensity score analysis, which attempts to reduce bias due to observed variables and attempts to mimic randomization. However, as the authors readily concede, the results of such a study must be validated in a prospective randomized study to provide more robust evidence of causal benefit."

One weakness is that the study did not try to assess whether starting patients on metformin after diagnosis might alter survival, he told Reuters Health by email. In addition, GI distress, a common side effect, may limit the agent's tolerability.

Dr. Boffetta told Reuters Health that his group plans to confirm their findings in a prospective analysis.

"The main weakness of the retrospective nature of the analysis involves factors that cannot be controlled but may affect results, such as the patients' other medications and the possibility that patients treated with metformin may have been better off than the patients who were not treated," he said. "We want to try to replicate these findings in a new cohort of patients where we can control these other factors."

The study received no outside funding.

SOURCE: http://bit.ly/2aCmTU0

Am J Gastroenterol 2016.