Diabetes without Drugs - The Metformin Story

New Research is showing that those with Type II diabetics need not rely on unpredictable drugs like Metformin for relief but may be better off introducing some simple lifestyle changes to fight the condition naturally.

As Europeans have become increasingly overweight and less active the number of people with diabetes has reached epidemic proportions. In the last decade the incidence of the disorder has risen by a third. By far the most common form of diabetes affecting around 95% of sufferers is type II diabetes (TTD). Unlike Type I diabetes where the pancreas is not producing enough insulin in TTD insulin levels are adequate but the body for unknown reasons cannot use it - something known as insulin resistance. Despite its prevalence up to a third of sufferers will go undiagnosed with the condition because of its very gradual onset and often asymptomatic nature1 which belies the symptoms of fatigue, nausea, frequent urination, unusual thirst, weight loss, blurred vision, frequent infections and slow wound healing that characterize the disease.

TTD is found most commonly in adults over 55 and about 80% of them will be overweight which makes it predominantly a lifestyle-dependent disease.1 It tends to run in families and researchers have identified a complex combination of many genes that may increase a persons risk for developing TTD as an adult.2 Although genetic predispotion is important it is obesity, a sedentary lifestyle and age that are the major risk factors in developing it. Indeed TTD used to be called "maturity-onset diabetes" because most people who get it are over 40 and overweight. But as more children become overweight TTD is becoming common in young people, so much so that an early onset form has been defined as Maturity Onset Diabetes of the Young or MODY. With the UK ranking as the fourth "fattest" country in the west children as young as five have been diagnosed with the condition according to doctors in Plymouth. And in Bristol children's hospital doctors have identified a form of diabetes normally affecting obese adults in a group of 13 year olds. Scientistss say that this has a lot to do with a western diet high in fat and refined sugars and low in fibre and exercise. Consequently treatment has mainly consisted of diet control, exercise and home glucose testing but because of the dramatic increase in TTD cases in recent years doctors are increasingly turning to drugs for solutions to the problem

Drug Therapies may be bad for your Health

But new research however is showing that frontline drug therapies may do more harm than good. Metformin (Tradename Glucophage) one of a few leading treatments continues to be used to treat TTD despite worries over side effects. It is the first biguanide (chemicals that mop up glucose) anti-diabetic agent to be approved by the American Food and Drug Administration (FDA) since its predecessor phenformin was taken off the market owing to reports of lactic acidosis - a condition resulting from an accumulation of lactic acid in the blood accompanied by symptoms like fatigue, breathlessness, abdominal pain and weight loss - and doubts concerning its long term benefit3 For nearly 17 years the U.S. market was devoid of an effective biguanide agent to treat the disorder during which time sulphonylureas became the only oral hypoglycaemic agents (TTD medicines) available but elsewhere in the world like Canada and Europe these drugs continued to be available and have produced mixed results. Research shows that Metformin can lower blood levels of glucose and increase the effectiveness of insulin therapy significantly through a double barrel action of enhancing uptake of glucose into the muscles and inhibiting glucose release from the liver. Not only that but studies show it is able to increase sensitivity to insulin, reduce blood cholesterol, triglycerides and even induce weight loss. Its no wonder then that Metformin had a reputation for being the top selling diabetes drug in the U.S. in 2000 single handedly responsible for creating $1.6 billion in revenues since its recent approval. 4
But despite Metformin's effectivness in many ways, recent reports have highlighted new worries over its alleged ability to induce lactic acidosis like Phenformin. Indeed in a communication in the Australian Adverse Drug Reaction Bulletin it has been reported that since its approval in that country Metformin use has been associated with 48 cases of lactic acidosis and 15 deaths. Lactic acidosis has been estimated to be fatal in up to 50% of cases. Back in the 70's phenformin caused hundreds of cases of lactic acidosis every year until it was taken off the market after a Health Research Group petition and lawsuit. Acting with the hope of preventing a similar tragedy some American authorities (like…) had blacklisted metformin from the outset claiming that its close chemical similarity to phenformin put individuals at risk of developing similar side effects.

When metformin was finally launched in the U.S. in its first month alone the FDA received 47 reported cases of lactic acidosis and of these 91% had one or more risk factors for its development owing to pre-existing conditions like heart disease, peripheral vascular disease, proteinuria (protein in the urine), pulmonary disease kidney problems or old age indicating that the drug may be grossly mis-prescribed despite label warnings on the insert. Since the FDA estimates conservatively that only 1 in 10 adverse effects ever get reported this would place the actual number of incidents at around 500 in the first month and more than 2000 since it was first introduced in 1996.4 In the U.S. at least the drug has now been forced to carry a black box warning by the FDA which is the strongest government requirement that can be imposed on a drug's sales.

Cutting your Diabetes Risk in half

Astonishingly diet and exercise have been found to delay diabetes and normalize blood glucose more effectively than the drug Metformin. Millions of sufferers of TTD can delay and possibly prevent the disease it has been found by making some simple lifestyle changes. Research indicates that while the oral diabetes drug Metformin also reduces TTD it is not as effective as diet and exercise modification.

In a large placebo-controlled study forming part of the Diabetes Prevention Programme, lifestyle intervention given by dietary changes and 150 minutes of exercise per week was proven to be more effective in reducing the development of TDD from cases of glucose intolerance than the drug metformin. The findings showed that participants in the lifestyle modification and metformin groups reduced their risk of TTD by 58% and 31% respectively. Whats more in the former case patients achieved an average of 7% weight loss which was sustained throughout the study.9

"This research conveys a powerful message of hope to individuals at risk for type II diabetes, a painful and life threatening disease that has been increasing in this country along with obesity" said HHS News secretary Tommy G Thompson "By adopting a moderate, consistent diet and exercise program, many people with one or more of the risk factors for Type II diabetes can stop the disease before it becomes irreversible"

Not only does lifestyle modification prevent or delay the development of diabetes but it was actually even shown to restore normal glucose levels to many who had already started to suffer with impaired glucose tolerance.

Metformin can actually increase the number of diabetes associated deaths

The UK Medicines Control Agency (MCA) has followed suit and advocate a cautious approach to the use of metformin in high-risk NIDDM patients They have alerted clinicians to immeadiately withdraw the drug and substitute with insulin therapy where required should such medical complications develop with pre-existing conditions like kidney failure or during surgery. The MCA claim this provision has resulted in a considerably lower incidence of metformin-associated lactic acidosis (around 2 per annum in the UK).5.

But apparently this does not alter the risks of its use. New data from a large 10 year follow up study on the drug - The United Kingdom Prospective Diabetes Study - has now vindicated concerns and showed that despite significantly lowering the incidence of lactic acidosis when compared with phenformin, metformin can still actually increase the number of diabetes associated deaths when taken with standard TTD treatments like sulphonylurea drugs as opposed to sulphonylureas alone especially where pre-existing conditions are present. (Sulphonylureas are accessory treatments that are usually indicated in TTD as adjuncts because not everybody responds to them and so they are often combined with a second drug.) Similarly another study conducted on patients attending the diabetes clinic at the Royal South Hants Hospital, Southampton were evaluated and only 41% were found to be free of risk factors or contraindications for the drug. The most frequent contraindications to metformin identified in this survey were ischemic heart disease (20 per cent of patients), and peripheral vascular disease (22 per cent). Two per cent of patients had severe renal impairment and 14 per cent had proteinuria. What's more multiple contraindications in individual patients were not uncommon. This suggests that if these results are representative of conditions throughout the UK many patients are taking metformin who should not be.6

For the meantime it is clear that implemented controls can only achieve so much and to a large extent preventing drug induced injury or death will depend on patient education and possibly the selection of an alternative drug or therapy where risk factors are present.

To that end researchers looking for alternatives have found that lifestyle changes may be just as important as drug therapies in combating the onset of TTD. In one study designed to assess the effects of lifestyle on impaired glucose tolerance which usually precedes the condition over 520 men and women in their 50's were judged to have halved their risk of developing it by focussing on weight reduction through reducing fat, increasing fibre intake and doing more exercise.7 Other research has reached similar conclusions such as a population study recently published in the New England Journal of Medicine which found that healthy lifestyle habits can reduce the risk of developing diabetes by more than 90%. This research followed the health habits of over 85,000 women and discovered that women with the lowest incidence of diabetes maintained a normal weight, exercised at least moderately for half an hour every day, followed a diet high in fibre, ate more polyunsaturated fats than saturated fats and were not cigarette smokers.8 A ten year follow up study has even confirmed that the more time we spend inactive watching TV the greater the risk we have for developing TTD. All of this puts the power back in to the hands of the patient and emphasizes that drugs do not always have the final word in healthcare.

Although it isn't easy to modify your diet and fit exercise into your daily schedule and sustain it studies have proven that in many cases these changes are lifesaving. If you are serious about cutting back your risk of developing TTD then you should consider lowering your fat consumption to 25% of your total calorific intake and walking vigorously for at least 30 minutes 5 days a week.

Fortunately if you're unable or unwilling to exercise or make changes to your diet there are lots of natural options available. Internet sites like alt.diabetes.com offer advice on selecting natural therapies like the herbal remedies glucosol, bitter melon, gymnema and fenugreek among others each of which has been clinically shown to help TTD by enhancing glucose tolerance, uptake or even increasing the number of viable insulin producing cells.

Make sure you discuss with your doctor the risks of Metformin and any concerns you may have. If you are presently on Metformin it is important that you do not take the natural remedies suggested above or stop taking the drug without first consulting your GP.

Resources
Organisations and Websites
http://www.diabetes.org.uk/
http://www.diabetes-self-help.co.uk/
Alternative Medicine
www.alt.diabetes.com
http://www.eating4health.co.uk/db_guide.html
Books
http://www.wellnessbooks.com/diabetes In particular the 5 star reference work Dr Bernstein's diabetes solution: A complete guide to achieving normal blood sugars. Richard K. Bernstein MD / Hardcover / Published 2000 Hardcover Little Brown and Company; ISBN: 0316093440

References
1. Diabetes Symptoms. http://www.diabetes-symptoms.org
2. Diabetes Type I and II. Odyssey Front Page. http://www.csu.edu.au/learning/ncgr/gpi/odyssey/diabetes/
3. The Drug Monitor - Metformin (Glucophage). http://www.home.eznet.net/~webtent/metformin.html
4. The Diabetes drug Metformin (GLUCOPHAGE) and Lactic Acidosis - A reminder about a potentially fatal adverse drug reaction. Worst Pills Best Pills July 2001 Vol 7 #7.
5. Contraindications to Metformin Therapy in Patients with NIDDM. Diabetes Care Vol 20 #6
6. Metformin in Type II diabetes needs monitoring. HEALTHINFOCUS.co.uk 1/10/997
7. Genes, Behaviour and environment. From "Whats Up Doc" Index for entries posted 14/8/01. The Centre for Applied Reproductive Science. http://www.ivf-et.com/wud010810.html
8. Cutting your Diabetes Risk in half. From John Hopkins "Health After 50" January 2002. http://www.hopkinsafter50.com
9. Diet and exercise delay diabetes and normalize blood glucose. HHS News - U.S. Department of Health and Human Services. Wednesday 6/2/2002