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LE Magazine September 2001
The Multiple
Benefits of Metformin
Metformin (brand name "Glucophage")
has been used in the treatment of type II diabetes for the
past 40 years.(1) This drug
counteracts many of the underlying factors that result in the
manifestation of this insidious disease. Metformin also
produces helpful side benefits that can protect against the
lethal complications of type II diabetes. Frequently
prescribed anti-diabetic drugs fail to address the fundamental
causes of type II diabetes and can induce serious side
effects.
by JoAnn
Knorr, MMS
Type II diabetes affects between 16 to 19 million
Americans. About 75% of type II diabetics will die from a
cardiovascular-related disease. Conventional doctors often
prescribe drugs for the purpose of lowering blood sugar
levels. These drugs do not adequately address the multiple
underlying pathologies associated with the type II diabetic
state.
Type II diabetes is characterized by cellular insulin
resistence. The result is excess accumulation of glucose in
the bloodstream as cells become resistant to the effects of
insulin.
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| Type II
diabetes is characterized by cellular insulin resistence.
The result is excess accumulation of glucose in the
bloodstream because cells become resistant to the effects
of insulin and fail to take up glucose. |
|
As the type II diabetic condition progresses, many people
gain weight and develop more fat cells.(2) Treating type II diabetes with
insulin-enhancing therapy increases the risk of cardiovascular
complications, induces weight gain, and fails to correct the
underlying cause of the disease. Many type II diabetics
produce too much insulin in a futile attempt to drive glucose
into insulin-resistant cells. When doctors prescribe
insulin-enhancing drugs to these type II diabetics, a
temporarily reduction of serum glucose may occur, but the
long-term effects of this excess insulin can be
devastating.
An ideal anti-diabetic drug would enhance cellular insulin
sensitivity, inhibit excess intestinal absorption of sugar,
reduce excess liver production of glucose, promote weight loss
and reduce cardiovascular risk factors. Metformin (Glucophage)
is the one drug that does all of this and more.
Metformin works by increasing the number of muscle and
adipocyte (fat cell) insulin receptors and the attraction for
the receptor. It does not increase insulin secretion, it only
increases insulin sensitivity. Therefore, metformin is not
associated with causing hypoglycemia. This activity reduces
insulin levels by increasing the sensitivity of peripheral
tissues to the effects of insulin by rejuvenating the
response, and restoring glucose and insulin to younger
physiological levels that may cause weight loss and most
certainly a decrease in the body's total fat content.(3-7)
In an study published by the American Diabetes Association,
metformin was found to decrease the fasting plasma glucose
concentration by -60 to -70mg/dl in patients with non-insulin
dependent type II diabetes.(1)
Metformin also reduced hemoglobin A1C levels, a blood
measurement of glycosylation. One of the most devastating
consequences of diabetes is protein degradation caused by the
formation of advanced glycated end products. Reductions in
serum hemoglobin A1C levels are a good indicator of consistent
glucose control in the diabetic patient.
Dr. Ward Dean is a specialist in anti-aging and life
extension medicine, author of over a 100 articles on the
biology of aging, and founder and Medical Director of the
Center for Bio-Gerontology in Florida. He recommends taking
500 mg of metformin two or three times per day to all his
patients over 40 who do not have kidney or liver problems, or
a history of congestive heart failure.(4,5)
According to Dean, aging causes insulin resistance.
Metformin increases hypothalamo-pituitary sensitivity that
declines with age. As we get older, there is a loss of
sensitivity of the hypothalamus and the peripheral tissues to
the effects of insulin, which causes elevated blood insulin
levels (hyperinsulinemia).(4,5)
A number of harmful and age-accelerating effects are
associated with elevated blood insulin levels. These effects
include: increased infections, microvascular complications
like retinopathy (eye problems), nephropathy (kidney
problems), neuropathies (nerve problems),
hypercholesterolemia, hypertension, premature atherosclerosis
and obesity, which eventually evolve into cardiovascular
problems.(1,3-5,8)
The cardiovascular system
Patients with type II diabetes often present with a cluster
of cardiovascular risk factors like visceral obesity,
hypertension, high triglyceride and low high density
lipoprotein (HDL) cholesterol levels, and hypofibrinolysis,
all of which form insulin resistance and potentially
contribute to increased cardiovascular risk.(8) In the United Kingdom Prospective
Diabetes Study, metformin was the only medication that reduced
diabetes related deaths, heart attacks and strokes.(1,8)
In the Fontbonne and Associates BIGPRO 1 trial, the
individuals with visceral obesity treated with metformin
showed greater weight loss, a greater decrease in fasting
insulin levels and a smaller increase in low density
lipoprotein (LDL) cholesterol concentrations than those who
received placebo. A decrease in plasminogen activator
inhibitor was most associated with the body weigh loss in
subjects.(8,9) In the trial, the
effects of metformin were most notable on the level of
endothelial (artery lining) damage that showed a decrease.
The microvascular complications of retinopathy,
neph-ropathy and neuropathy improve due to metformin's ability
to decrease damage to arterial lining.(2) These small blood vessels are
somewhat unblocked to provide healthier blood supply to vital
tissues surrounding the eyes, kidneys and nerves.(2)
The potentially preventive effects of metformin on type II
diabetes and evolving cardiovascular complications include a
decrease in total cholesterol and low density cholesterol
(LDL), free fatty acids, tissue plasminogen activator antigen
and insulin levels when patients present with symptoms of
hypertension, dyslipidemia, visceral obesity or
hyperglycemia.(8)
In non-diabetic patients with hypertension, 3 placebo
controlled trials were done. These trials showed that
metformin significantly reduced fasting insulin or C-peptide
levels, as well as total cholesterol, low density lipids
cholesterol or apolipoprotein B levels, fasting free fatty
acids and tissue plasminogen activator antigen levels.
Metformin had a significant effect on lowering blood pressure
and fasting triglyceride levels in one of these trials.(8)
Polycystic ovarian syndrome
Polycystic ovarian syndrome is characterized by irregular
or absent menstrual periods, and elevated serum testosterone
and androstenedione. These patients complain of abnormal
bleeding, infertility, obesity, excess hair growth, hair loss
and acne. Polycystic ovarian syndrome seems to have a genetic
component in which those who are affected often have both male
and female relatives with type II diabetes, obesity, elevated
blood triglycerides or high blood pressure. They may also have
female relatives with infertility, hirsutism or menstrual
problems.
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| Metformin
has been found to suppress the growth of some tumors and
enhance the activity of anti-cancer drugs. |
|
For women in the reproductive age range, polycystic ovarian
syndrome is a serious common cause of infertility because of
the endocrine abnormalities that accompany elevated insulin
levels. As women with polycystic ovarian syndrome maybe at
greater risk for other medical conditions, testing is
essential. They should be tested for blood lipids, diabetes
and blood clotting factors that promote abnormal clotting.
Metformin, at doses of 500 mg to 850 mg three times per day,
has been shown to reverse these endocrine abnormalities. In
women with polycystic ovarian syndrome, metformin reduced
systolic blood pressure, hyperinsulinemia and insulin
resistance, and facilitated menstrual regulation and
pregnancy.(10,11)
Cancer & cellular immunity
Metformin has been found to suppress the growth of some
tumors and enhance the activity of anti-cancer drugs. By
giving the immune system a boost, metformin can improve
cellular immunity. It has also been found to reduce the
incidence of chemically induced cancer in rats.(5,7)
The way metformin improves cellular immunity is linked to
its blood sugar lowering effect by improving receptor
sensitivity and number. Bacteria, fungi and some viruses tend
to feed on sugar. By diminishing their fuel supply, we
diminish them. That is why diabetics and other individuals
with endocrine abnormalities tend to be more prone to
infections.(2)
Contraindications & side effects
Metformin is not recommended for people who have a history
of kidney or liver disease, or a history of congestive heart
failure. People with a history of alcohol abuse should also
avoid taking the drug, as serious lactic acidosis can develop
in these individuals.
Long term use of metformin may cause malabsorption of
vitamin B12.(1,3-5,8) Because of
the depletion of B12, supplementation is recommended.4-6 When
a person begins to take metformin, they may experience some
nausea and vomiting, stomach pain, bloating and diarrhea. The
latter usually disappear once the person becomes accustomed to
the drug.(1,5)
Many helpful side benefits
Metformin's multiple effects benefit individuals with a
propensity to develop diabetes, cardiovascular problems,
endocrine problems, retinopathies, nephropathies, cancer or
decreased immunity, infections and weigh gain.(1-5,8)
As with diabetes, metformin has been shown to cause a
reduction in appetite, weight, and the body's total fat
content. In associated heart disease conditions, there is
plaque build-up that lines the arteries. This build-up of
plaque can lead to atherosclerosis.(8) Metformin reduces or lowers the
chances of developing atherosclerosis and reduces the rate of
pro-aging cross linkages of collagen, which plays a role in
the scar tissue build-up that cccurs during wound
healing.(4)
Metformin has been shown to reduce the amount of
supplemental insulin needed by type II diabetics who become
insulin-dependent. They are able to take a lower insulin dose
in conjunction with metformin without the risk of becoming
hypoglycemic. For 40 years metformin has been used to control
blood glucose levels in patients with type II diabetes.
Physicians are recommending it to patients who are predisposed
to diabetes for the prevention of developing the disease.(8)
 |
| Metformin
prevents the acceleration of atherosclerosis and reduces
the rate of pro-aging cross linking of collagen. |
|
With the cluster of cardiovascular problems associated with
hyperinsulinemia, metformin has proven effective in lowering
total cholesterol, low density lipids, free fatty acids,
tissue plasminogen activator antigen and insulin levels when
patients present with symptoms of hypertension dyslipidemia,
visceral obesity or hyperglycemia. Metformin prevents the
acceleration of atherosclerosis and reduces the rate of
pro-aging cross linking of collagen. The microvascular
complications of hyperinsulinemia are improved by metformin
due to the arterial clearance in small blood vessels of the
eyes, kidneys and nerves.
There are other positive effects associated with metformin:
decreased tumor growth and improved cellular immunity in
individuals who are prone to chronic infections associated
high blood sugar levels. In non diabetics, metformin reduced
low density lipid, total cholesterol, free fatty acids, tissue
plasminogen activator antigen, blood pressure and fasting
triglyceride levels.(1-5,8)
Women suffering from polycystic ovary syndrome have been
treated with metformin. Benefits include: lipid lowering
effects, reduction in systolic blood pressure,
hyperinsulinemia and insulin resistance syndrome. Metformin
has also been shown to aid in normal menstrual regulation and
pregnancy.(10,11)
In conclusion, the scientific research points to
metformin's multiple uses, with few drawbacks. Accordingly,
the drug's numerous side benefits associated with the
treatment and prevention of diabetes, as well as other
disorders, appear to outweigh its limited side effects.
Metformin
Dosage Suggestions
References
1. Cusi, K., DeFronzo, RA. Metformin: a
review of its Metabolic effects. Diabetes Reviews. V6 N2
1998:89-131.
2. Merck. The Merck Manual of
Diagnosis and Therapy. Section 2. Endocrine and
Metabolic Disorders. Chapter 13. Disorders of Carbohydrate
Metabolism.
3. Dean, Ward. Biological Aging Measurement Clinical
Applications. The Center for Bio-Gerontology, Pensacola,
Florida, 1988.
4. Dean, Ward. Metformin: Life Extension Drug - Weight Loss
Drug. International Anti-Aging System. Vol.: 2291.
5. Dean, Ward. Metformin: The Most effective Life extension
Drug. International Anti-Aging System. Vol.: 801.
6. Deutsch, J.C., Santhosh-Kumar, C.R., Kolhouse, J.F.
Efficacy of Metformin in non-insulin-dependent diabetes
mellitus. NEJM, 1996, 334,
4: 269. Dilman, Vladimir, and Dean, Ward.
7. Dilman , Vladimir, and Dean, Ward. The Neuroendocrine
Theory of Aging, The Center for Bio-Gerontology, Pensacola,
Florida, 1992.
8. Charles, M.A., Eschwege, E. Prevention of Type 2 Diabetes:
Role of Metformin. Drugs
1999;58 Suppl.1:71-73.
9. Fontbonne A., Charles MA, Juhan-Vague I, et al. The effect
of Metformin on the metabolic abnormalities associated with
upper body fat distribution. Results of the BIGPRO 1 trial.
Diabetes Care 1996;
19:920-6.
10. Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith L.
Metformin induced resumption of normal menses in 39 of 43
(91%) previously amenorrheic women polycystic ovary syndrome.
Metabolism 1999;
48:1-10.
11 Valazquez EM, Mendosa S, Hamer T, Sosa F, Glucck CJ.
Metformin therapy women with polycystic ovary syndrome reduces
hyperinsulinemia, insulin resistance, Hyperandrogenemia, and
systolic blood pressure, while facilitating menstrual
regulation and pregnancy. Metabolism 1994, 43:647655.
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