Diabetes and Cancer: Can Metformin Treat Both?

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A study published in Diabetes Care in January of 2012 showed that patients with diabetes are more likely to develop cancer than people without diabetes and that adults with diabetes are more likely to die of cancer than their non-diabetic counterparts.

The association between diabetes and cancer was first noted over 100 years ago, but physicians have become increasingly aware of this association only in the last few years as recent studies have demonstrated that having diabetes increases the risk of almost all types of cancer.  The risk of pancreatic, liver, and endometrial cancer is approximately twice that of the non-diabetic population. Some studies have reported a similar increase in the risk of bladder cancer and in cancers of the oral cavity. The risk of kidney cancer is reported to be approximately 40% higher, and cancer of the colon approximately 30% higher in diabetic individuals compared to those without diabetes.  Diabetes is also associated with an increased risk of breast cancer, and those with diabetes are more likely to present with advanced stage breast cancer and are more likely than those without diabetes to die from breast cancer. Notably, studies have reported that the risk of developing prostate cancer is lower in those with diabetes, although in men who develop prostate cancer, diabetes is associated with a greater risk of mortality, recurrence, and treatment failure.

The Link Between Diabetes and Cancer

Why the association between diabetes and cancer occurs is still unclear. Type 2 diabetes is characterized by insulin resistance, which means that the pancreas needs to secrete much more insulin in order to compensate and help sugar go from the blood to the tissues.  The high levels of insulin that result from insulin resistance might be responsible for the increased rates of cancer seen in patients with diabetes, as has been seen in animal models of colorectal and pancreatic cancers.  Another possible mechanism is that high blood glucose itself is contributing to this association.

Many studies around the world are currently underway to help understand the connection between diabetes and cancer.  In the meantime, the increase in cancer risk means that physicians who treat patients with diabetes must be aware of this association and should be making sure that patients get the appropriate cancer screenings done on time.

Metformin as an Anticancer Agent

Another piece of the diabetes and cancer puzzle is the drug metformin (glucophage).  Metformin, a first line therapy for diabetes, seems to be emerging as a potential anticancer agent.  The primary actions of metformin include reducing the insulin resistance and also decreasing the production of sugar by the liver. This results in lower circulating glucose and plasma insulin levels.

A few years ago it was noted that diabetics had an increased cancer mortality compared with non-diabetics, as mentioned above, but that diabetics on metformin had a substantially (40%) reduced cancer burden compared with diabetics on other treatment. Since then, several population-based studies have suggested that metformin reduces cancer incidence and/or mortality among type 2 diabetic patients treated with metformin. For example, a study that was done in Scotland involved 11,876 patients with newly diagnosed diabetes which were followed from 1993 to 2001.  Results showed a 15% reduction of cancer risk in patients on metformin, looking at all types of a cancer together.  Another study published in Diabetes Care in February 2012, followed 8,392 patients with diabetes and showed that metformin was associated with survival benefit both in comparison with other treatments for diabetes and in comparison with a nondiabetic population. The studies show that the effect seems to increase the longer the patients take metformin.

This protective effect of metformin can also be seen in studies which looked at specific cancers, for example, liver, prostate, pancreas, breast, and ovaries.  A study published last month looked at effect of diabetes and diabetes medications on ovarian cancer treatment and outcomes.  It included 341 ovarian cancer patients.  Of these, 297 did not have diabetes, 28 were patients with type 2 diabetes who did not use metformin, and 16 were patients with type 2 diabetes who used metformin.  Despite the fact that all three groups received similar treatment for their cancer, their survival at five years was very different–  63% for the diabetic patients who used metformin, 37% the non-diabetic patients, and 23% for the diabetic patients who did not use metformin.

Another study showed that patients with type 2 diabetes receiving neoadjuvant chemotherapy for breast cancer as well as metformin were more likely to have a complete remission than patients not receiving metformin.

The consistency and magnitude of the cancer-lowering effect seen in these studies have generated a great deal of enthusiasm.  Several prospective studies are now being done to more accurately describe this phenomenon in patients with and without diabetes.   Also, scientists are trying to clarify by what molecular mechanisms metformin is acting as an anti-tumor agent.

If the research continues to show good results for metformin, we’ll have at our fingertips a safe, inexpensive, generic drug with relatively few side effects that could be used not just to treat diabetes, but to prevent or help to treat cancers in patients with and without diabetes.

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