Glucophage

Glucophage is the brand name for metformin, a widely used oral medication for the treatment of type 2 diabetes. Metformin belongs to a class of drugs known as biguanides, and it works by helping to control blood glucose levels. It is particularly popular for its ability to improve glucose control without causing hypoglycemia (low blood glucose), a common side effect of many other antidiabetic drugs.

Mechanism of action of metformin:

1. Decreasing glucose production in the liver - Metformin reduces the amount of glucose produced by the liver.
2. Improved insulin sensitivity - enhances the body's ability to use available insulin to manage blood glucose levels more effectively.
3. Lowering blood glucose levels - Metformin helps reduce the absorption of glucose from food in the intestines.

Indications Glucophage

Glucophage is commonly used to treat type 2 diabetes mellitus. It can be used alone or in combination with other hypoglycemic agents or insulin. Glucophage is also indicated to prevent the development of diabetes mellitus in individuals with prediabetes and to improve insulin sensitivity in patients with polycystic ovary syndrome.

Release form

Glucophage (metformin) is usually available in tablet form.

Pharmacodynamics

1. Decreasing Gluconeogenesis: Glucophage reduces the production of glucose in the liver (gluconeogenesis), which is the main mechanism of its antihyperglycemic action. It inhibits enzymes involved in the process of gluconeogenesis, such as phosphoenolpyruvate carboxykinase (PEPCK) and gluconeogenesis-11.
2. Increased tissue sensitivity to insulin: Metformin increases tissue sensitivity to insulin, allowing it to better utilize glucose from the blood. This is especially important for muscles, which become more sensitive to insulin, which helps improve peripheral glucose uptake.
3. Decreased intestinal glucose absorption: Glucophage may reduce intestinal glucose absorption from food, resulting in decreased postprandial glucose peaks and decreased postprandial hyperglycemia.
4. Lowering Blood Lipids: Glucophage may also have beneficial effects on blood lipid levels, including lowering triglycerides and total cholesterol.
5. Oxidative stress and antioxidant activity: There is evidence that metformin may reduce oxidative stress and have antioxidant properties, which may be related to its protective effect on cardiovascular events.

Pharmacokinetics

1. Absorption: Metformin is absorbed from the gastrointestinal tract, primarily in the upper intestine. Absorption is slow, with peak concentrations usually reached approximately 2.5–3 hours after administration.
2. Metabolism: Metformin is practically not metabolized in the body. It is excreted unchanged through the kidneys.
3. Elimination: The primary route of metformin excretion is renal. Most of the drug is excreted unchanged through the kidneys. In patients with impaired renal function, metformin may be retained in the body, requiring dosage adjustment or discontinuation of the drug.
4. Half-life: Metformin's half-life is approximately 6.2 hours, allowing it to be taken two or three times daily, depending on your doctor's recommendations.
5. Food effects: Food can affect the rate and extent of absorption of metformin, so the drug is usually taken with or immediately after meals.

Dosing and administration

Directions for use:

1. Taking with food: Glucophage should be taken with or after meals to minimize gastrointestinal side effects such as nausea and diarrhea.
2. Regularity: The medicine should be taken regularly, according to the schedule prescribed by the doctor, to maintain stable blood glucose levels.

Dosage:

The dosage of Glucophage depends on the individual patient's needs, response to treatment and target blood glucose levels.

1. Initial dose: The usual starting dose is 500 mg once or twice a day or 850 mg once a day. Your doctor may gradually increase the dose to improve blood glucose control.
2. Maintenance dose: The usual maintenance dose may range from 1500 to 2000 mg per day, divided into two or three doses.
3. Maximum Dose: The maximum recommended dose is 2550 mg per day for adults. For extended-release forms of metformin, the maximum dose can be up to 2000 mg per day.

Special instructions:

• Gradual increase in dose: To minimize side effects, it is advisable to gradually increase the dose.
• Monitoring: Regular monitoring of renal function is necessary, especially before starting treatment and periodically during treatment, since metformin is excreted by the kidneys.
• Discontinuation: Metformin should be temporarily discontinued before certain medical procedures or if conditions develop that may increase the risk of lactic acidosis (eg, severe dehydration or hypoxia).

Use Glucophage during pregnancy

Recommendations for the use of metformin during pregnancy:

1. Type 2 diabetes:

   • Glucophage may be recommended during pregnancy to manage type 2 diabetes. Some studies have shown that it may be safe and effective during this period, helping to control blood glucose levels without a significant risk of hypoglycemia.
   • However, the standard treatment for gestational diabetes is insulin, and metformin should only be used under strict indications and physician supervision.

2. Polycystic ovary syndrome (PCOS):

   • Glucophage is used to improve insulin resistance in women with PCOS, which may help promote regular menstrual periods and improve ovulation. This may be helpful for women trying to get pregnant.

3. Safety and effectiveness:

   • Studies suggest that metformin may be relatively safe to use during pregnancy, but more data is still needed to confirm its complete safety. It is important to consider that metformin crosses the placenta, and its effects on the fetus require further study.

4. Monitoring and management:

   • If Glucophage is prescribed during pregnancy, careful monitoring of the mother's health and fetal development is necessary. This includes regular blood glucose checks, as well as possible ultrasound examinations to assess the condition of the fetus.

Contraindications

1. Renal impairment: Metformin is excreted via the kidneys and its accumulation in the body may lead to the development of lactic acidosis in patients with poorly functioning kidneys. Therefore, Glucophage is contraindicated in patients with severe renal impairment (glomerular filtration rate less than 30 ml/min) or moderate renal impairment in the presence of other risk factors.
2. Hepatic impairment: In patients with severe hepatic impairment, Glucophage may be contraindicated due to possible impairment of metformin metabolism and elimination.
3. Alcoholism: In case of alcohol abuse, metformin may increase the risk of lactic acidosis. Therefore, patients with alcohol dependence or severe alcohol abuse are not recommended to use Glucophage.
4. Ketoacidosis: Glucophage is also contraindicated in the presence of ketoacidosis, a serious complication of diabetes characterized by high levels of ketone bodies in the blood.
5. Allergy: Patients with a known allergy to metformin or other components of the drug should avoid its use.
6. Pregnancy and breastfeeding: Use of Glucophage during pregnancy and breastfeeding requires consultation with a doctor due to limited information about its safety in these situations.

Side effects Glucophage

1. Gastrointestinal disorders: diarrhea, nausea, vomiting, abdominal pain, decreased appetite.
2. Metallic taste in the mouth.
3. Lactic acidosis (a rare but serious complication characterized by increased levels of lactate in the blood) may develop.
4. Rarely, allergic reactions may occur, including hives and itching.

Overdose

1. Lactic acidosis: This is a serious complication that can occur if you take an overdose of metformin. Lactic acidosis is characterized by a buildup of lactic acid in the body. Symptoms may include nausea, vomiting, abdominal pain, muscle weakness, fatigue, difficulty breathing, decreased body temperature, and changes in mental status. Treatment involves fluid replacement and correction of acid-base balance.
2. Hypoglycemia: In rare cases, metformin may cause hypoglycemia (low blood glucose), especially in people with kidney problems or other conditions that may impair metformin metabolism. Treatment involves taking carbohydrates and monitoring blood glucose levels.
3. Other side effects: Other side effects associated with metformin overdose are also possible, such as gastrointestinal disorders, headache, hypovitaminosis B12, and others.

Interactions with other drugs

1. Antidiabetic drugs: The combination of metformin with other antidiabetic drugs such as sulfonylurea or insulin may result in an increased hypoglycemic effect. This may require dosage adjustment.
2. Drugs that affect kidney function: Drugs such as some nonsteroidal anti-inflammatory drugs (NSAIDs), antihypertensive drugs, or diuretics may affect kidney function and the levels of metformin in the body.
3. Drugs that affect acid-base balance: Drugs, including carbonates, acetazolamide, and others that can change the acid-base balance in the body may affect the blood levels of metformin.
4. Drugs that affect digestion: Drugs that decrease or improve digestion, such as antiemetics or antacids, may interfere with the absorption of metformin.
5. Alcohol: Drinking alcohol may increase the risk of lactic acidosis while taking metformin.
6. Other Medicines: Before starting a new medicine in combination with Glucophage, it is important to consult with your doctor to assess potential interactions and adjust the dosage if necessary.