New study shows type 2 diabetes drug metformin could modulate cancer growth

Camille Bienvenu
Mon, 18 Apr 2016
New study shows type 2 diabetes drug metformin could modulate cancer growth
A recent study conducted by the Roswell Park Cancer Institute, looking into the incidence of different long-term diabetes treatment on the development of certain cancers in post-menopausal women, has found metformin to be the most effective at lowering cancer mortality.

The Assistant Professor of Oncology at Roswell Park, Zhihong Gong, teamed up with investigator Jean Wactawski-Wende from the Women's Health Initiative to analyse information gathered on 145,826 women aged 50 to 79 years-old of 40 U.S. clinical centres in the course of five years of research led by the organisation back in 1993.

They found that the participants with diabetes were exposed to a 45% greater risk of death from invasive cancer overall than women without diabetes. And among women with diabetes, those managing their condition with metformin benefited from better survival rates for ovarian, colorectal and breast cancer, as a direct effect of prolonged exposure to the drug.

An insight into this came into from previous studies showing that cancer cells are able to grow and reproduce following the warburg anaerobic metabolic pathway whereby cancer cells defaults to using glucose to make ATP.

The reason for that being that this is that most cancers seem to have defects in their mitochondria preventing them from carrying out oxidative phosphorylation and resorts to glucose as their preferred fuel source

Additional retrospective studies taking into consideration factors such as body weight and other medications in diabetic patients who take metformin came to similar conclusions, and attributed the drug's ability to inhibit cancer cells growth to the activation of an enzyme called AMP kinase, which plays a role in suppressing the production of glucose in the liver, from where it is released to the rest of the body.

This strategy is part of a paradigm shift that has come about in oncology where a way to treat and even prevent cancer would be to exploit this metabolic abnormality and reduce the bio availability of glucose to effectively starve cancer cells, either by exogenous means via a drug or through the diet. A variable that would need to be taken into consideration in further randomized controlled trials looking at the link between diabetes and cancer therapy. Low-carb ketogenic type-diets in particular are getting traction as complementary cancer treatment.

For the time being researchers say further studies are needed to clarify the long-term impact of metformin on cancer risk as, from a purely scientific perspective, correlation doesn't always imply causation.

The results provided by this study alone do not enable us to draw clear conclusions as to what mechanism specifically drive better cancer outcomes, whether it is because the glucose levels of patients taking metformin were lower or because they needed less insulin. Insulin and insulin-like growth factor (IGF-1) could also influence cancer growth in people with defective IGF-1 receptors, or it could be that caloric restriction (often synonymous with glucose restriction) induced by reduced cravings as a result of normalised blood sugar with metformin is what keeps cancer at bay too.

At any rate, the evaluation of the therapeutic efficacy of glucose and/or insulin reduction via the diet is gaining momentum and other clinical trials are underway investigating the metformin effect on other forms of cancer (endometrial, cervical, prostate, pancreatic, colon) sensitive to this metabolic effect.
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