A Diabetic Drug and Cancer

Summarized by Robert W. Griffith, MD
November 21, 2005

Introduction

It's bad enough having diabetes, without having to worry all the time about possible side effects of medication. Now there's a little good news for people taking metformin (Glucophage®). A study reported in the British Medical Journal suggests that they have a slightly reduced risk of developing cancer. Here's a summary of the research findings.

What was done

In Scotland there are two large databases that can be linked: a diabetes clinical information system (DARTS) and a database of dispensed prescriptions (MEMO).

This allowed the researchers from Dundee to analyze the frequency of long-term metformin use in patients with and without cancer.

Out of more than 300,000 people dying in the Tayside area between 1993 and 2001, 11,876 had type 2 diabetes. Of these, 923 were admitted to hospital with cancer, more than one year after their diagnosis of diabetes. These patients formed the 'study group'. Two 'control patients' were selected at random from the diabetes patients who didn't have cancer, one for each study-group patient. These were matched, as far as possible, with regard to age, gender, and year of diagnosis with their study-group patient.

Information on the use of metformin was gathered and analyzed statistically, taking into account possible bias from the following factors: smoking, body mass index (BMI), and blood pressure.

What was found

Just over half the patients with cancer were men. The average age was 73, and they had had type 2 diabetes for an average of 8^1/2 years.

Just over a third of the cancer cases and the controls had been treated with metformin in the year before their cancer diagnosis was made.

Taking metformin was associated with an overall 21% reduction in cancer risk, compared with the control group. Adjustment for factors such as smoking, obesity, and blood pressure gave a 23% reduction in cancer risk. For those patients who had been taking metformin for more than 5 years, the reduction in risk was 46%.

What these results may mean

Patients with diabetes have an increased risk of cancer, particularly liver and pancreatic cancer ¹. This study suggests that the risk of cancer-related deaths may be influenced by the choice of antidiabetic therapy. One of the researchers has commented: "Taking metformin may be associated with reduced risk of cancer in patients with Type 2 diabetes, and a biologically plausible mechanism exists".

The possible mechanism is as follows. Metformin works by targeting an enzyme (AMPK) that causes muscles to take up glucose from the blood. A precursor of this enzyme (called LKB1) is a well-recognized tumor suppressor; activation of AMPK by metformin stimulates LKB1 (as does exercise, another anti-cancer factor).

The type 2 diabetics in this study were receiving antidiabetic medication. Those not on metformin were almost certainly receiving a sulfonylurea drug, such as glyburide or tolbutamide. One possibility, therefore, is that sulfonylureas have a pro-cancer effect, rather than metformin showing an anti-cancer effect. Either way, a Clinical Task Force of the International Diabetes Federation has now recommended metformin for starting oral treatment of type 2 diabetes.

Obviously further studies will be done to shore up, or refute, this additional role of metformin. Meanwhile, for diabetics on the drug, these findings are good news, of a sort.

Source

• Metformin and reduced risk of cancer in diabetic patients. EJMM. Evans , DLA. Donnelly , EAM. Emslie-Smith,  et al., BMJ, 2005, vol. 330, pp. 1304--1305

Footnotes
1. Diabetes mellitus and cancer. CA. Czyzyk , SZ. Szczepanik , Eur J Intern Med, 2000, vol. 11, pp. 245--252

Related Links
When Diet Is not Enough for a Type 2 Diabetic
Diabetes: Type 2
Statins Reduce the Risk of Coronary Artery Disease in Type 2 Diabetics

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