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Novel therapeutic uses of Metformin

Diabetes, Heart, General, Women's Health | September 1, 2015 | Author: The Super Pharmacist

heart, diabetes

Novel therapeutic uses of Metformin

Metformin is predominantly used as an oral antidiabetic drug for the treatment of type 2 diabetes. The active ingredient metformin hydrochloride (also known as metformin hcl) helps the body to control blood sugar by lowering the amount of sugar created by the liver and decreasing the amount of sugar absorbed by the intestines.

What is the relationship between metformin and reducing the risk of cancer?

Metformin is also often used off label, and research looking at its role in diabetes control has revealed that it may also be beneficial in reducing the risk of developing a number of different cancers in patients with type 2 diabetes. As the role of metformin in cancer reduction is a relatively new development, most of the studies that have been conducted so far have predominantly been carried out on mice. The first link between Metformin and lowered cancer risk, established by a team of American scientists in 2012, found that metformin prevented primary liver cancer (hepatocellular carcinoma) in mice, and that mice who had received the drug experienced substantially fewer tumours and reduced levels of glucose than those who did not receive the dose (1). A 2015 study, published in the World Journal of Hepatology, both metformin and statins had been evidenced to reduce the risk of hepatocellular carcinoma by an estimated 50-60% (2). Whilst the initial studies have been very promising, there remains a limited number of clinical trials data to examine the anti-cancer benefits of metformin in reducing the incidence of liver cancer in a human population. The studies that do exist do also record a significant benefit to being treated with metformin Novel therapeutic uses of Metforminmonotherapy, with a 2012 retrospective cohort study of 110,000 diabetes patients in the UK concluding that general cancer patients who also have type 2 diabetes experience a significantly reduced mortality rate compared to cancer patients without diabetes (3). The relationship between monotherapy and the treatment or development of cancer still requires further testing due to a wide range of potentially confounding variables. The study also points out that patients with diabetes are linked with improved lung cancer survival when compared to non-diabetics, although the nature of this potential causal relationship requires further testing and explanation. The same study reported that the presence of diabetes substantially increased mortality in both breast and prostate cancers, and the relationship between these patients and metformin monotherapy remains unclear. A more recent study, again undertaken with mice, has found metformin to be effective in preventing aggressive ovarian cancer (4). However, as this study is solitary and unique in its content, there are no clinical trials data on human populations to corroborate these findings.

Does metformin have a role to play in reducing cholesterol?

There is a strong evidence base highlighting the role of metformin in reducing cholesterol. It does this by improving the lipid profile beyond only its glucose lowering effects by also reducing triglyceride and cholesterol synthesis. The drug has been shown to reduce triglycerides by around 10% (5,6) and low density lipoprotein cholesterol by 10-15% (7,8). Due to the weight of the evidence behind both its safety and efficacy, it is regularly used in clinical practice and is also a strong contributor to weight loss in patients with diabetes.

Is there any substance behind the claim that metformin is an ‘anti-ageing’ drug?

A number of articles and research summaries have recently suggested that metformin may have anti-ageing properties following a number of trials on rodents. Both hyperglycaemia and hyperinsulinaemia are important factors in both ageing and cancer, and a number of studies have shown that the inactivation of insulin and/or insulin-like signalling has increased the lifespan of a number of different species including fruit flies, monkeys and mice (9). Although a number of different studies have shown that metformin decreases insulin resistance, extends lifespan, and reduces carcinogenesis in rodents (10,11), no such trials currently exist that suggest metformin (or any other antidiabetic biguanides) will increase the lifespan of humans.

Is metformin currently being used for any other purpose than diabetes?Novel therapeutic uses of Metformin

Metformin is regularly used to address a wide range of other health conditions. As well as being used to treat diabetes, it is also used as a preventative measure, in conjunction with dietary changes and an exercise programme, to prevent diabetes in patients identified at risk of developing the disease. Many women who have polycystic ovarian syndrome (POCS), a common hormonal disorder that interferes with the growth and release of eggs from the ovaries, are prescribed metformin. In most countries metformin is not licensed to treat this condition and is used off-label, although many clinicians consider that the drug does has positive benefits for POCS patients and clinical prescribing is ahead of the existing evidence base in regards to both its safety and efficacy (12). However, official guidelines in many countries advise against its use, stating that the benefits to patients are only moderate and can often be offset by a range of other side effects including hirsuitism and increased levels of acne. Although the drug is regularly prescribed to help patients with menstrual regularity, it has been proven to be less effective than drugs specifically marketed for this condition such as co-cyprindiol (13). A number of observational studies and RCTs have suggested that metformin is clinically effective and safe in the management of gestational diabetes, but there are no long term studies regarding its safety or any potentially adverse effects on mother and/or child. For this reason, non-pharmaceutical methods for mothers with gestational diabetes, such as a focus on a food plan and moderate exercise, tend to be the treatment of choice for most physicians.  

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REFERENCES:

  1. Bhalla K, Hwang BJ, Dewi RE, Twaddel W et al (2012) Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis Cancer Prev Res 5(4):544-52
  2. Ampuero J, Romero-Gomez M (2015) Prevention of hepatocellular carcinoma by correction of metabolic abnormalities: roles of statin and metformin World J Hepatol 7(8):1105-11
  3. Currie CJ, Poole CD, Jenkins-Jones S et al (2012) Mortality after incident cancer in people with and without type 2 diabetes Diabetes Care Available online at care.diabetesjournals.org/content/early/2012/01/02/dc11-1313.full.pdf (last accessed 15th August 2015)
  4. Al-Wahab Z, Mert I, Tebbe C, Chhina J et al (2015) Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction Oncotarget 6(13):10908-23
  5. DeFronzo RA (1999) Pharmacologic therapy for type 2 diabetes mellitus Ann Intern Med 131(4):281-303
  6. DeFronzo RA, Goodman AM (1995) Efficacy of metformin in patients with non-insulin dependent diabetes mellitus N Engl J Med 333:541-9
  7. Shaw RJ, Lamia KA, Vasquez D et al (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin Science 310(3754):1642-46
  8. Jeppesen J, Zhou MY, Chen YD et al (1994) Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM Diabetologia 37(8):781-7
  9. Anisimov VN (2013) Metformin: do we finally have an anti-ageing drug? Cell Cycle 12(22):3483-9
  10. Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, et al (2012) Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study Nature 489:318–21
  11. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein Science 292:104–6
  12. Harborne L, Fleming R, Lyall H, Norman J, Sattar N (2003) Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome Lancet Published online at http://image.thelancet.com/extras/02art6157web.pdf (last accessed 16th August 2015)
  13. Polycystic ovary syndrome: metformin in women not planning pregnancy NICE Guidance Available online at https://www.nice.org.uk/advice/esuom6/chapter/key-points-from-the-evidence (last accessed 16th August 2015)
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