Metformin

Glucophage (metformin HCL) 

The drug belongs to a group of drugs called the 
biguanides. A group of antihyperglyceimic drugs. 
Others include Buformin and Phenformin. These 
drugs increase the transport of blood sugar 
across the cell membrane into muscle cells. The 
action works by positively effecting cellular 
insulin sensitivity.

Metformin is very similar to Phenformin that is also an oral hypoglycemic except that Phenformin is considered the harsher of the two compounds. Phenformin is considered to be from 5 - 10 times stronger than Glucophage at what it does for the body on a mg. per mg. comparison. Glucophage has significantly less side effects than Phenformin has as well. The chance for an overdose causing hypoglycemia with the use of Glucophage is dose related whereas you almost have to take a lethal dose. It is common knowledge that Glucophage will increase insulin sensitivity as well. Most bodybuilders use Metformin for its “safety.”

Glucophage is the brand name for the oral anti-hyperglycemic agent metformin HCL. It is generally used in the 
management of mature onset (Type-Il) diabetes and utilized when dietary management and exercise alone have not been able to control the disease, yet injectable insulin is not appropriate since this hormone is still present in the body. 

When your body releases insulin, over time, your insulin receptors get 'dull', less responsive. In advanced stages that becomes type II diabetes. Metformin 'refreshes' those receptors, making them more sensitive to the insulin that your body releases. Metformin enhances the effect of insulin and by now we all agree insulin is the single most anabolic agent available. The discovery of how to use insulin correctly in bodybuilding, has without a doubt revolutionized bodybuilding. It has produced competitors twenty pounds heavier. Now many bodybuilders choose the usage of simple carbohydrates or Metformin to manipulate insulin as a safer option. It is also possible to combine insulin – metformin and simple carbs. Later more about that.

While the main activity of Glucophage (metformin HCL) is the increased utilization of glucose, it does not directly mimic the action of insulin. The precise mode of action is actually unknown, but it is believed to increase insulin sensitivity through some peripheral process. Use of Glucophage (metformin HCL) will certainly lower the patient's blood sugar, but its activity makes it unlikely to cause a state of hypoglycemia if the dosage of Glucophage is accidentally misjudged (a major concern with injectable insulin). As far as bodybuilders are concerned, this product is used as an oral form of insulin. It will cause greater glycogen super compensation during carb-ups as well as lowering blood glucose for those that are using a ketogenic diet.  I already posted on the lipolytical properties of metformin here: //juicedmuscle.com/jmblog/content/metformin-fatloss

Metformin  and Insulin effects

The concept of harnessing insulin for performance enhancement has been catching on in recent years. As you may know, insulin is considered a "storage hormone". Injectable insulin can be extremely risky however, an incorrect dosage or insufficient carbohydrate intake having grave consequences to the user's health. In extreme cases, hypoglycemia (low blood sugar) can lead to coma or even death. Since this effect is rare with Glucophage, it is considered by many athletes to be an introduction to insulin manipulation.

Diabetics (type I and ll) are, with help of Metformin able, to control their blood sugar and insulin very well. Very often their blood work comes back better than that of a non-diabetic. It’s not surprisingly therefore that metformin is thought to increase lifespan. More on that later.

Some diabetics use other medication that helps regulate their blood sugars even more, such as Invocana  (Canagliflozin). 
They help to spill over excess sugar into the urine. High blood sugars are the ones that will cause you the most damage. Lows can be immediately risky, but are not the culprit of all 
the complications associated with diabetes in the long run.

Dosage and use

When administered, the absorption rate of Glucophage (metformin HCL) is very slow. Metformin HCL will make its way to circulation slowly, over a period of about six hours, with the half-life being as long as 15 hours. 

Metformin (also sold under the brand name Glucophage) comes in a regular version which is taken at meal time, three times a day, and an extended release form (marketed as ER or XR) which is taken once a day. Almost always, when people report diarrhea or intense heartburn with metformin, they are taking regular version. I experienced the heartburn on the regular drug. The ER version releases the drug more slowly 
and this usually eliminates the gastrointestinal problems.

The trade off with taking the ER form is that the amount of blood sugar lowering you see might be a bit less than with the regular form as the drug acts in a slower smoother fashion rather than hitting all at once. But if you can't take the regular at all drug because of the side effects, the slight weakening in effect is a reasonable trade off. Plus, you only have to remember to take one dose rather than three. 

One important point is this: The maximum dose of Metformin ER is LOWER than the maximum dose of regular Metformin.According to the prescribing information, the maximum dose of the ER is 2000 mg a day. That of the regular is 2550 mg/day.

The dose at which metformin is supposed to be effective for most people is 1500 mg per day, though I know some 
smaller people who find a dose of 1000 mg effective. Your body weight will make a difference here, so if you are very large, you may need the maximum dose. In any event, don't conclude that metformin doesn't work until you have tested the dose up to the maximum. 

It also takes up to two weeks for the full effect of metformin to become evident. While you will see an increase in your blood sugars if you forget a single day's dose, if you stop the drug for two weeks you will notice see a slow rise in blood sugars through this period. My guess is that this two stage effect is because metformin works both on the liver (where it reduces the release of glucose) and the muscle (where it tricks the tissue into thinking it has just exercised and thus ramps up its burning of glucose). Whatever the explanation, give the drug a few weeks to see what it really does.

Also, many people who experience gas after taking metformin find that cutting way back on their intake of starchy 
carbohydrates helps eliminate the problem. If you take Metformin ER or XR in the evening you’ll end up having to get up to pee at night more than usual. So you may considder to take it in the morning. 

Glucophage XR extended-release tablets may rarely cause a serious and sometimes fatal condition called lactic acidosis. Most of these cases have occurred in diabetic patients who also have certain kidney problems. The risk of lactic acidosis may be greater if you have liver problems, kidney problems, or heart failure. The risk may also be greater in patients who are elderly or drink alcohol. Do not take it if you have a severe infection, have low blood oxygen levels, or are dehydrated.

The general intake schedule among bodybuilders is to take 850mg (one tablet) twice per day. The user will be sure to additionally supplement with a carbohydrate replacement (such as weightgainer) and with Creatine monohydrate, particularly after periods of training. The result of Glucophage's treatment will probably not be as dramatic as whenusing insulin, but a notable anabolic effect can be achieved nonetheless. 

Others want  better results and build up slowly to three tablets (of 850 mgs) a day taken morning, noon and night using a three day on one day off regime. They combined it with indictable insulin. The top athletes took on 1 IU per 10 KG of bodyweight three times a day. They were careful to use the Humilin act rapid S and take 10 grams of carbs and five grams of whey protein 90 minutes after administration.

For example 100 1KG man would take three metformin tablets a day. 10 IU of insulin first thing in the morning, 1090 grams Maltodextrin and 50 grams of whey 90 minutes later. This he would repeat early afternoon and early evening.

The most successful subject also took 50 MCG of T3 on the days they took the metformin and 4 IU GH as two separate 2 I U shots taken mid-morning and thirty minutes after training.

Most athletes opt to use this drug for a limited duration, cycles of Glucophage usually lasting only a couple of months. This would be followed by an equally long break (at a minimum). 

Common side effects of Glucophage are a metallic taste in the mouth, nausea, and vomiting. You have to take the tablets with meals and with half liter of water to avoid stomach upset.

This will become on the next big drugs used by professional bodybuilders in the coming years for its ability as a repartitioning agent and blood glucose disposal agent. 

Effective Dose: 1,700 mg. per day in divided doses. These tablets degrade in sunlight and need to be kept cool

It is a great product. Taken straight after a large meal, within the hour you will have EXTREMELLY full muscles. Dosages are 500mg after a normal to large carb meal, 1,000mg after a big carb meal and 1,500mg after all you can eat at Pizza Hut.  You can take it after as many meals in a day as you wish, as long as those are large carb meals.

I generally found that if I take less than 100g of carbs for every 500mg metformin, I go into hypo. And yes, you can eat fat meals, as metformin will indirectly prevent the fat being deposited.

The long acting glucophage is taken before bed as it helps the person release less insulin throughout the night, especially if they had a big dinner like most people do. But that doesn't apply to a healthy person. That might get a healthy person in hypo overnight.

I believe every human should be on metformin, as it helps keep your insulin receptors fresh and as such it will prevent type II diabetes

On some discussion forums people will tell you taking Metformin for bodybuilding works contra-productive. They base themselves on a study from 2002 After metformin administration, there was a significant reduction in serum level of total testosterone, free testosterone, and 17 hydroxyprogesterone. There was also a significant increase in serum level of sex hormone binding globulin (p=0.009) and dehydroepiandrosterone sulphate. If you train as a “natural” they can be right, but imo most people also inject AAS during cycling.

Metformin could increase lifespan

A new study sheds new light on a diabetes drug that controls glucose, suggesting it could have preventative capabilities and even increase lifespan.

A new study sheds new light on a diabetes drug that controls glucose, suggesting it could have preventative capabilities and even increase lifespan.

A large-scale study conducted by researchers at Cardiff University says that type 2 diabetes patients live longer than people without the disease thanks to surprising benefits of their medication, metformin, which could be expanded for use in non-diabetics.

Murmurs of metformin's attributes had been circulating within the scientific community, and the findings of the Cardiff study not only build on its benefits but are of particular interest due to the massive sample size of 180,000 participants.

Researchers compared survival rates of type 2 diabetes patients taking metformin, a first-line therapy, with those of patients on a less-prescribed diabetes drug called sulphonylurea, known for undesirable side effects such as weight gain and hypoglycemia.

"What we found was illuminating," said lead author Professor Craig Currie from Cardiff University's School of Medicine.

According to Dr. Currie, patients undergoing metformin treatment exhibited small yet statistically important survival increases by comparison to non-diabetics.

As for those treated with sulphonylureas, their rate of survival was consistently reduced when compared to that of non-diabetics.

"This was true even without any clever statistical manipulation," says Dr. Currie.

Researchers used data from the UK Clinical Practice Research Datalink, representing around 10% of the UK population.

They identified 78,241 patients who were prescribed metformin as a first-line therapy and 12,222 patients prescribed a sulphonylurea as a first-line therapy.

Each patient was then compared to a non-diabetic.

Patients with type 2 diabetes are often forced to resort to more aggressive treatment options as their disease 
progresses, so a long life expectancy is no guarantee, although Dr. Currie plans to concoct a long-term treatment plan for diabetics to circumvent this transition.

Metformin is inexpensive and has exhibited preventative capabilities in the domains of cancer and cardiac disease.
Dr. Currie points out that it can prevent those at risk for diabetes from actually developing the disease and he says his findings indicate that the drug could be beneficial for those with type 1 diabetes.

Anti-Diabetes Medication may also suppress cancer

Research at the university of Leuven (Belgium) shows that metformin, the drug most widely used against diabetes, possibly suppresses certain cancers and cardiovascular diseases. Scientists think that metformin could promote an overall healthy aging.
They have shown how Metformin works to do so. Metformin increases the production of harmful oxygen species in the mitochondria, the "energy plants" of a cell. Because that happens in moderation, that is a good thing.

To provide the body cells with energy, the mitochondria are generating small electric shocks. Sometimes thereby 
releasing oxygen species which can damage proteins and DNA. But as long as there is no excessive amount of these particles released at the same time, they have long-term positive effect.

The cells absorb the oxygen species before they cause damage and then even stronger. "Metformin causes a slight increase in the number of harmful oxygen species, thus causing the cells to become stronger and their healthy lifespan is longer." 

It was thought that these harmful oxygen species were causing aging. The food and cosmetics industry played on that with products that contain antioxidants. Think of skin creams, fruit and fruit juices, red wine or dark chocolate.
Antioxidants neutralize harmful oxygen species and would thus delay aging.

This theory is not true: since the action of metformin just depends on which oxygen species, antioxidants prevent the life-prolonging effect.

For their study, the scientists used the tiny roundworm Caenorhabditis elegans. This worm lives only three weeks, and is therefore the ideal animal to study aging.

As they grow older, these worms are shrinking and wrinkling, and they move less. Worms treated with metformin, do not exhibit these aging signs. They hardly shrink and show no wrinkling. So the worms do not only age slower, they also remain healthy longer.

Metformin and Growth Hormone

You can find many studies about Growth Hormone causing insulin insensitivity. A few are:

Growth Hormone Replacement Therapy Induces Insulin Resistance by Activating the Glucose-Fatty Acid Cycle.

Growth Hormone Replacement Therapy Can Raise Incidence of Type 2 Diabetes

Over time Growth Hormone  use can make you insulin 
resistant. In some people insulin sensitivity goes bad 
very quickly when they are using Growth Hormone or
peptides. For that reason some people are unable to use 
GH, because they start storing fat quickly. They are then 
afraid of developing Diabetes type II. It’s  therefore best 
to check your blood sugar  regularly while on GH.

Some have blood very high blood sugar readings after a 
heavy carb meal when using GH. High blood sugar is known to be very unhealthy.

It’s for that reason that many bodybuilders combine 
Growth Hormone with Metformin, mostly along with a 
low dose of T3.

Metformin is although found to prevent liver cancer

Metformin, a well-tolerated drug prescribed for diabetics, may also protect against liver cancer, says a new study. The study, led by Geoffrey Girnun, assistant professor of biochemistry and molecular biology at the University of Maryland School of Medicine, looks at the effect of metformin in cancer prevention and is one of the first to evaluate liver cancer.

“Since many of the effects of the drug take place in the liver, we were surprised when we reviewed the literature that there was no direct evidence for a protective effect of metformin in liver cancer except for a few retrospective 
epidemiological studies,” Girnun was quoted as saying in the journal Cancer Prevention Research.He and his colleagues chemically induced liver tumours in mice. These mice taking metformin displayed minimal tumour activity, while the control mice (not given metformin) displayed significant tumour growth, said a university statement.

Girnun’s team also showed that metformin prevented liver cancer in part by inhibiting lipid synthesis in the liver, a 
process known to promote cancer. Diabetics, obese individuals, patients with hepatitis or patients with non-alcoholic fatty liver disease are at the greatest risk for liver cancer.