Metformin improves outcomes for cancer patients with type 2 diabetes

In cancer patients with concurrent type 2 diabetes, metformin alone or in combination with other regimens was associated with 34% reduction in overall death risk and 38% reduction in cancer-specific death risk, according to a study in the December issue of The Oncologist.   

A team of researchers led by Ming Yin, MD, at Geisinger Medical Center in Danville, Pa., performed a meta-analysis to evaluate the association of metformin treatment and both overall and cancer-specific survival. They searched for relevant publications as of July 1, 2013, in English literature in electronic MEDLINE and PubMed databases. A meta-analysis was performed to investigate the association between metformin and overall survival as well as cancer-specific survival in a total of 13,008 cancer (pancreas, colorectal, ovary, breast, prostate, bladder, liver, larynx, and lung) patients with concurrent type 2 diabetes.

Slightly less than half of the cancer patients underwent metformin treatment either alone or in combination with other glucose-lowering therapies. The remainder of the patients received only non-metformin therapies to control their diabetes. The analysis demonstrated that metformin treatment was associated with a significantly lowered risk of death 34%, compared with no metformin treatment. Even after excluding the largest study from the meta-analysis, which accounted for nearly 40% of the total participants, the results did not change significantly. In fact, a sensitivity analysis, which involved excluding one study at a time from the analysis, revealed that no single study influenced the overall conclusion: patients treated with metformin consistently did better.

Over the last 4 years, a number of studies have compared the survival outcomes of diabetic cancer patients treated with metformin with those treated with other drugs; however, the results from individual studies of different cancers were inconsistent. Dr. Yin and colleagues identified 20 studies of patients with cancer and concurrent diabetes, which also reported survival data according to metformin treatment. They then employed statistical methods commonly used in meta-analyses to adjust for confounding variables, heterogeneity between studies, and publication bias.

They also evaluated the differences among the individual cancer types. Using one analysis, a fixed-effect model, they found that a significant metformin-associated reduction in risk of death was seen in breast, prostate, pancreatic, and colorectal cancer but not in lung cancer. Using the more conservative random-effects model, significantly lower risk of death was observed for pancreatic and colorectal cancer, but only a trend toward lower risk was observed for breast, prostate, and lung cancer. When stratifying by global region, metformin-treated patients in both Eastern and Western countries independently saw improved survival compared with their non-metformin-treated counterparts.

 “Hospital decision-makers may provide education materials to healthcare providers about this finding and encourage them to apply metformin in cancer patients with concurrent type 2 diabetes, except lung cancer due to equivocal effect in this patient population,” said Dr. Yin.

According to Dr Yin, there are several take-away points:

• Diabetes and cancer are not two separate irrelevant diseases, but are biologically related. There is evidence that diabetes patients have increased cancer risk and cancer-related mortality

• If there are no contraindications, cancer patients with concurrent type 2 diabetes should be advised to use metformin or metformin-containing regimen for their diabetic control, except lung cancer. “This is because metformin or metformin-containing diabetic treatment is associated with increased overall survival and cancer-specific survival,” Dr. Yin said.

• There is insufficient evidence to suggest metformin use in lung cancer patients with concurrent type 2 diabetes

• The mechanisms of survival benefit associated with metformin are mediated by direct effect of tumor inhibition and indirect effect of not inducing hyperinsulinemia, compared with other diabetic medications

• Metformin treatment is relatively safe in cancer patients. “It is not carcinogenic and does not promote tumor growth,” he said.

The study appears with a commentary by Carlo La Vecchia, MD, and Cristina Bosetti, PhD, which critically examines the evidence of the impact of metformin on cancer risk and prognosis.