Metformin - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

This oral hypoglycemic drug belongs to the group Biguanide, an AMP-dependent protein kinase (AMPK) activator. Metformin was introduced in 1950 and was found to be an oral hypoglycemic drug that works to overcome insulin resistance. When compared to other oral hypoglycemic drugs, Metformin causes little or no hypoglycemia in nondiabetic subjects and even in people with diabetes. It does not stimulate pancreatic beta cells, and it is reported to improve lipid profile as well in type 2 diabetics.

Composition:

This tablet contains,

1. Active Ingredient: Metformin hydrochloride.

2. Inactive Ingredient:

• Carboxymethylcellulose.

• Sodium.

• Colloidal silicon dioxide.

• Hypromellose.

• Magnesium stearate.

• Microcrystalline cellulose.

Drug Group:

Metformin is an oral hypoglycemic drug and belongs to the group biguanide (AMPK activator). It is a prescription medicine, which comes as an oral tablet and solution.

What Is Metformin Used For?

The uses of Metformin are as follows:

1. Type 2 Diabetes Mellitus:

• Metformin is now established as a first-choice drug for all type 2 diabetes mellitus patients, except when not tolerated or contraindicated.

• The given dose is 0.5 to 2.5 g/day in 2-3 divided doses after food.

• It can be given as a monotherapy or combination with other oral antidiabetic drugs or Insulin.

Recommendations-

It is recommended for,

• Obese patients.

• Insulin-resistant diabetic patients.

• In primary or secondary Sulfonylurea failure patients.

Advantages-

• Metformin does not cause hypoglycemia (as a side effect) even in large doses.

• It does not result in weight gain and may cause weight loss.

• It also reduces hyperlipidemia, that is,

1. Decreases - Low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), cholesterol, and triglycerides (TGs).

2. Increases - High-density lipoproteins (HDL).

• Metformin decreases microvascular and macrovascular events in type 2 diabetes mellitus patients.

• It helps to decrease the risk of diabetic endpoint diseases, for example,

1. Myocardial infarction (MI).

2. Stroke.

3. Renal failure.

4. Amputation.

• It has an antihyperglycemic efficacy (HbA1c reduction by 0.8–1.2 %) equivalent to other oral drugs.

• There is no acceleration of beta-cell exhaustion or failure in type 2 diabetes mellitus.

• It can be combined with any other oral or injectable antidiabetic drugs if one drug is not adequate.

Controlling High Blood Sugar Prevents-

• Blindness.

• Kidney problems.

• Sexual function.

• Loss of limbs.

• Heart attack.

2. Polycystic Ovarian Syndrome:

It improves ovulation and fertility in some infertile women with polycystic ovaries.

How Does Metformin Work?

Biguanides do not cause the release of Insulin, but Insulin is essential for their action. It has been recognized that activation of AMP-dependent protein kinase (AMPK) plays a crucial role in mediating the actions of Metformin. AMPK activation results in,

• The indirect consequence of interference with cellular respiration.

• A decrease of intracellular ATP.

• A decrease in other energy sources.

Actions:

• Antihyperglycemic and not Hypoglycemic agent - It does not stimulate the pancreas to secrete Insulin and does not cause hypoglycemia even in large doses.

• Metformin reduces plasma glucose levels by -

1. Inhibiting hepatic gluconeogenesis and glucose output from the liver. This is the major action responsible for the lowering of blood glucose in diabetics.

2. Metformin increases insulin-mediated glucose uptake and distributes it in skeletal muscle and fat tissues. Insulin resistance exhibited by people with type-2 diabetes is thus overcome. This translates into:

1. Glycogen storage in skeletal muscle.

2. Decreased lipogenesis in the adipose tissue.

3. Increased fatty acid oxidation.

• Slows the intestinal absorption of sugars and vitamin B 12 - Metformin obstructs the mitochondrial respiratory chain and enhances peripheral glucose utilization through the process of anaerobic glycolysis. Metformin also retards intestinal absorption of,

1. Glucose.

2. Hexoses.

3. Amino acids.

4. Vitamin B 12.

Onset Of Action:

Metformin has 50 to 60% of oral bioavailability under fasting conditions and is not metabolized or bound to plasma proteins, and is excreted unchanged in the urine. It is generally slowly absorbed and reaches its peak plasma concentration at 1.5 to 3 hours of taking an immediate-release tablet and 4 to 8 hours of taking an extended-release tablet. The duration of action is 6 to 8 hours, so one to two doses are taken per day.

Expiry Date:

Avoid taking this medicine after it expires. Please verify the expiry date printed on the back of the pack before taking medicine.

What Is the Dosage and Administration of Metformin?

Dosage and administration of Metformin depends on the following,

• Age of the patient.

• Medical condition or history of the patient.

• Patient’s response to treatment.

Preparations and Doses:

The available forms of Metformin for both adults and children are,

Metformin Dosage for Elderly patients:

• Elderly patients who have diabetes are more prone to get decreased renal function, and so this drug is given cautiously with close monitoring.

• This drug is contraindicated in patients with renal impairment.

• This drug should not be given to patients above 80 years of age with renal failure.

How to Use Metformin?

1. For starting Metformin and stopping or continuing the old drug, for example, on taking Chlorpropamide (another diabetic drug), it is important to follow the doctor's instructions carefully.

2. It is important to check the blood sugar levels regularly as instructed by the doctor.

3. Always keep track of the blood sugar readings, and share them with your doctor on the next appointment.

4. Read the leaflet if available before starting Metformin and if you have any questions, ask the doctor or pharmacist.

5. It should be taken orally, 1 to 2 times a day, with meals as directed by the doctor, and drink plenty of fluids.

Missed Dose:

In case if you miss the dose, the missed dose can be taken as soon as you remember it. But if it is time for the next dose, you do not want to take the missed dose, and you can continue with your regular dosing schedule. Also, do not take a double dose in order to compensate for a missed one.

What Are the Drug Warnings and Precautions?

1. Do not use this medication if you have already been allergic to Metformin and its ingredients. Always check the label to know the list of ingredients.

1. Tell your doctor or pharmacist if you have any other allergies.

1. The following conditions predispose to increased lactate production, which causes lactic acidosis, which is fatal. They are,

• Renal failure.

• Advanced Liver Disease.

• Cardiac Disease.

• Chronic lung disease.

• Severe peripheral vascular disease.

• Shock.

1. Tell your doctor about your medical history, especially of,

• Severe asthma.

• Obstructive lung disease.

• Vitamin B 12 deficiency.

• Anemia.

• Liver disease.

• Kidney disease.

1. Surgery or Other Procedures - If you are going to have surgery or any procedure, tell your doctor about all the prescription, nonprescription, and herbal supplements you are taking because they may instruct you regarding the drug intake (in case you may need to stop the medication for a short time) before surgery.

1. Be extra cautious while dealing with heavy machinery, driving, or doing any activity because Metformin can cause drowsiness, dizziness, blurred vision, etc.

1. Avoid Alcohol - It is better to avoid alcohol while using this medication because it has increased risk for developing,

• Lactic acidosis.

• Low blood sugar.

1. Lactic Acidosis - Limit the use of diuretics (water pill); also, high fever, sweating, diarrhea, and vomiting may cause dehydration and increase the risk of lactic acidosis. So, inform your doctor when any of these symptoms persist for the long term.

1. Do not be stressed and feel relaxed by following a proper diet and exercise because stress increases the level of blood sugar.

1. Pregnancy - Metformin should be used when it is absolutely needed and instructed by the doctor at the time of pregnancy. It is better to switch to Insulin when you are pregnant, so consult with your doctor about the risks and benefits of Metformin.

1. Breastfeeding - Metformin passes through the breast milk, so consult your doctor during the period of lactation.

1. Menstrual Cycle - Metformin changes the pattern of the menstrual cycle and increases the chances of pregnancy, and promotes ovulation. So, ask your doctor if any birth control pills are needed before using this medicine.

What Are the Side Effects of Metformin?

Side effects with Metformin are frequent but generally not serious.

1. Hypoglycemia - Metformin does not cause or minimal hypoglycemia except in overdose. It occurs when only combined with other agents.

2. Gastrointestinal (GI) Side Effects - The limiting feature is GI intolerance, which occurs especially on the usage of higher doses of the drug. This drug is established to cause serious toxicities after decades of use. It is associated with the following usual complaints, which tend to subside with time and can be decreased by taking with meals.

• Metallic taste.

• Anorexia.

• Nausea.

• Vomiting.

• Bloating.

• Mild diarrhea.

• Tiredness.

• Abdominal discomfort.

3. Vitamin B 12 and Folic Acid Deficiency - It occurs on prolonged use and due to malabsorption of Metformin.

4. Weight Loss - It can be used in obese patients.

5. Lactic Acidosis - The small increase in blood lactate occurs with Metformin because it is poorly concentrated in hepatic cells. It results in renal failure and increases the risk of lactic acidosis, which is rare (<1 per 10,000 patient-years) but serious. Alcohol ingestion can also precipitate lactic acidosis.

In addition to general restrictions for the use of oral hypoglycemics, Metformin is contraindicated in the following due to the increased risk of lactic acidosis.

• Hypotensive states.

• Heart failure.

• Severe respiratory disease.

• Hepatic and renal disease.

• Alcoholics.

6. Skin rashes.

What Are the Drug Interactions of Metformin?

Metformin has serious, mild, and moderate drug interactions with certain drugs, and all drugs that interact with Metformin are not mentioned here.

• Avoid alcohol with Metformin as it is known to interact with it and cause irritation.

• Excretion of Metformin is affected, and its toxicity is increased when it interacts with the drugs like,

1. Cimetidine.

2. Furosemide.

The list of some other drugs that interact with Metformin are,

• Metformin decreases the excretion rate of Abacavir, Abemaciclib.

• Bepridil.

• Acemetacin.

• Acetyl sulfisoxazole.

• Capmatinib.

• Escitalopram.

• Acetyl sulfisoxazole.

• Acarbose, when combined with Metformin, results in hypoglycemia.

• Acebutolol.

• Aceclofenac.

• Dabrafenib.

• Acetazolamide.

• Fenoldopam.

• Acetohexamide.

• Acetylsalicylic acid.

What Are the Common Brand or Trade Names of Metformin?

The common brand names of Metformin are,

• Riomet.

• Glucophage.

• Glucophage XR.

• Fortamet.

• Glumetza.

• Zomet.

• Etformine.

• Insumet.

• Zoform.

• Bigomet.

• Diamet.

• Irmet.

• Metomin.

• Metlead SR.

• Metsar.

• Forminal SR.

• Metbay.

• Metadoze.

• Metday.

• Dibeta.

• Metgem.

• Okamet.

• Xmet.

• Obimet.

• Metlong.