Metformin Hydrochloride History
Metformin has a long and fairly complicated history in medicine. This drug was first synthesized in 1929 along with a series of other biguanides. Although some of its beneficial properties were elucidated at the time, it was not initially subject to human trials. It sat idle in the research books for nearly three decades after its creation. The first clinical study investigating its therapeutic potential as a glucose lowering medication was finally initiated in 1956. These trials were very successful, and metformin was selected for clinical development. It was given the trade name Glucophage, which translates to “glucose eater”. This, of course, refers to its ability to help the body dispose of blood glucose. Glucophage went on to be the most recognized trade name for metformin HCL. This trade name is still being used to market the drug today, presently by the Bristol-Myers Squibb Company.
Metformin was not initially the glucose-lowering agent of choice among clinicians. During the 1950s, it had been studied alongside phenformin and buformin, which had also been selected for commercial development. Metformin was initially pushed aside in favor of these two drugs, both of which had proven to be significantly more potent at lowering blood sugar levels. These drugs would remain the dominant biguanides for approximately 20 years. By the 1970s, however, it was being reported that phenformin and buformin were producing unacceptably high incidences of lactic acidosis, an often-fatal metabolic disorder characterized by a rapid drop in pH. By the close of the 1970s, most governments had determined that these drugs were too risky to continue using. Phenformin and buformin were subsequently removed from most pharmaceutical markets worldwide.
The structural and pharmacological similarity of metformin to phenformin and buformin held back its clinical potential for many years. Researchers were widely concerned that this agent would also present unfavorable risks.While lactic acidosis is a legitimate concern, it occurs much less frequently than with the other biguanides (approximately 1 in 33,000 patients). Following much evaluation of its benefit-risk ratio, metformin eventually came to be regarded as the safest drug of the biguanide class. It was widely pushed back into clinical medicine during the mid-1990s. It was introduced to the United States in 1995, where it was an immediate success. In the years to follow, metformin continued to grab a stronger share of the global diabetes medication market. Today, it is estimated that metformin HCL is the most widely prescribed medication for the treatment of type-2 diabetes.
How is Metformin Hydrochloride Supplied
Metformin hydrochloride is most commonly supplied in oral tablets of 500, 850, and 1000 mg each.
Structural Characteristics of Metformin Hydrochloride
Metformin is a synthetic derivative of the natural antidiabetic agent guanide. It is specifically the 1,1- dimethylated biguanide variant.
Metformin Hydrochloride Warnings
In rare cases, the use of metformin HCL is associated with lactic acidosis, an often-fatal metabolic disorder involving (among other factors) an increase in lactate levels (lactic) and a pronounced decrease in blood pH (acidosis). This risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, and acute congestive heart failure. Symptoms of lactic acidosis include malaise, muscle pain, respiratory distress, drowsiness, and abdominal distress. Laboratory abnormalities include low pH,increased anion, and elevated blood lactate. If lactic acidosis is suspected, metformin HCL should be discontinued and the individual should seek immediate medical attention.
Metformin Hydrochloride Side Effects
Common side effects of metformin HCL therapy include diarrhea (53.2%), nausea/vomiting (25.5%), flatulence (12.1%), weakness (9.2%), indigestion (7.1%), abdominal discomfort (6.4%), and headache (5.7%). Metformin must be used with caution in patients with renal dysfunction, and impaired creatinine clearance. A serum creatinine concentration above 1.5 mg/dL (men) or 1.4 mg/dL (women) is considered a contraindication to treatment. Metformin may also impair the absorption of vitamin B12. Hypoglycemia is uncommon with the use of metformin, though is sometimes noted when caloric intake is deficient, or when strenuous exercise is not compensated by caloric supplementation. Minor side effects often subside over time, or with use of a lower metformin HCL dosage. Lactic acidosis has been reported in approximately 32% of metformin HCL overdose cases (see: WARNINGS).
Metformin Hydrochloride Administration
The oral absorption rate of metformin HCL is slow, with the body taking approximately six hours to absorb and distribute each dose. Extended release (XR) formulations are also made, which further delay the absorption of metformin HCL. Extended release tablets should be taken whole, and not crushed. In a clinical setting, the drug is given in divided doses with meals, except for extended release formulations, which are administered once daily with the evening meal. There is no set adult clinical dose, and the drug must be tailored to and the drug must be tailored to the individual needs of the patient. It is typically initiated at a low daily dosage, and slowly escalated by 500 mg each week or 850 mg every two weeks until the minimum daily dose required for adequate glycemic control has been established. The maximum recommended daily dose for type-2 diabetic patients in 2550 mg per day. Fasting plasma glucose is used to determine the therapeutic response to metformin HCL, and glycosylated hemoglobin levels are measured every three months. The goal of therapy is to decrease fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal levels using the lowest effective dose of metformin HCL, either alone or in combination with another antihyperglycemic drug (sulfonylurea or insulin).
When used for physique or performance-enhancing purposes, the typical protocol is to take 850 mg once or twice per day. If a single application is desired, it is typically taken 1-2 hours before exercise, so that the drug can have its peak effect during the early stages of recovery. It is highly common to utilize a carbohydrate supplement during the hours metformin is active in the body, especially during the crucial 2-3 hour “nutrient uptake” window following intense training. The result of metformin treatment is typically not as dramatic as insulin, but the drug still does have a notable anabolic effect for many users. Most bodybuilders/athletes opt to use this drug for a limited duration, with cycles lasting 6-8 weeks in length. This would be followed by an equally long break (at a minimum) before metformin, insulin, or any other antihyperglycemic agent is used for physique or performance-enhancing purposes.
Metformin Hydrochloride Availability Trends
Metformin is readily available given its widespread use in clinical medicine. It is sold under many brand names, as both a standalone and combination medication. Bodybuilders and athletes tend to limit their use to preparations containing only metformin.While the drug is not the subject of much interest by steroid counterfeiting or underground manufacturing operations, it is the target of many other general drug counterfeits given the ease in which it can be sold. As such, it should not be assumed that all packaged drug products labeled as metformin are legitimate. Care should be taken to ensure that all products bearing this ingredient have been acquired through legitimate pharmaceutical channels.
Glucophage is an antidiabetic drug prescribed to treat Type II diabetes. Type II diabetes is also called non-insulin-dependent diabetes mellitus. Individuals who have Type II diabetes are usually unable to produce enough insulin naturally (in response to the food they ingest) or suffer cell insulin receptor-site insensitivity. However, Glucophage can be prescribed by a doctor for Type I diabetics as a means of additional glucose (blood sugar) control in unison with insulin injections.
Clinical use of Glucophage for diabetics is fairly common. What the drug does is:
- Increase cell insulin receptor-site number and sensitivity.
- Decreases the amount of glucose/sugar the intestines absorb.
- Decrease the amount of glucose/sugar the liver manufactures. (One source of liver glucose production is amino acids/protein).
These three effects explain why clinical administration of Glucophage seldom results in reports of added hypoglycemic effects during administration of the drug alone. However, when combined with insulin injections and/or sulfonylureas (Glipizide) a significant increase in carbohydrate requirements and weight gain is realized.
Polled bodybuilders utilized the effects of Glucophage differently for different phases;
1. During mass gain phases utilizing exogenous insulin, 500-850 MG 1-2 times daily of Glucophage increased the effective value of insulin. This was due to an elevation in receptor-site number and sensitivity. Glucophage also decreased the amount of insulin needed for maximum results.
2. During pancreatic regeneration or protocols that included Glipizide, Glyburide, or other pancreatic/insulin stimulation, Glucophage increased the effectiveness and amplified results. 500 MG 2 x daily was the common Glucophage dosage for this purpose.
3. During diet phases, bodybuilders have utilized Glucophage as a means of decreasing glucose production by the liver and glucose absorption by the intestines. This in itself decreases insulin secretion by the pancreas and increases the body's dependence upon fat stores for energy requirements. This was employed especially so during GH and PGF-2 use, and was synergistic with anabolic/androgenic steroids. SINCE cell insulin receptorsites are more sensitive and since there is an existing cross-over stimulation between IGF-1 and Insulin (and their opposing receptor-sites) lean mass retention was notably increased. This effect helped decrease the negative effects dieting has upon IGF-1 production endogenously.
*Since less IGF-1 is produced during diet phases, less lean mass is normally retained. If cell receptor-sites are more plentiful and sensitive, less IGF-1 is required for stimulation. 500MG daily of Glucophage was usually considered effective for this.
Glucophage was taken with meals and never less than 6 hours before sleeping. Individuals with kidney problems did not take Glucophage and most athletes were aware of the fact that in some cases stacking with oral 17-alfa-alkylated drugs could induce even greater liver damage.
The drug insert gives some insight into the potential dangers of non-monitored use:
Combining Glucophage with Digoxin (Lanoxin), furosemide (Lasix), or any diuretic is dangerous for individuals with heart problems. Glucophage has also been known to encourage lactic acidosis. Lactic acidosis is a build-up of lactic acid in the blood stream. Prolonged excessive lactic acid build-up in blood can cause serious damage. Alcohol use increases the risk of lactic acidosis during periods of Glucophage use. A doctor should be consulted for monitoring prior to use.
Wlliam Llewellyn (2011) - Anabolics
L. Rea (2002) - Chemical Muscle Enhancement Bodybuilders Desk Reference