Metformin : The Trusted First-Line Medicine For Type 2 Diabetes

Introduction of Metformin

When someone is diagnosed with the Type 2 Diabetes, one of the first medicines doctors often prescribe is Metformin. For more than 60 years, it has been one of the most widely studied and trusted Diabetes medication in the world. It helps lower the blood sugar level effectively, has a low risk causing hypoglycaemia when used alone, and most importantly, it is affordable. And may even offer additional health benefit beyond the glucose control.

MOA

Metformin helps lower blood sugar in people with type 2 diabetes without making the body produce more insulin. Instead, it works in several smart ways:

Reduces sugar made by the liver: The liver naturally releases sugar into the bloodstream. Metformin slows down this process, especially between meals and overnight.

Decreases sugar absorption: It reduces the amount of sugar your body absorbs from food in the intestines.

Helps your body use insulin better: Metformin makes your muscles and other body tissues more sensitive to insulin, allowing glucose (sugar) to move from the blood into the cells where it is used for energy.

Unlike some diabetes medicines, metformin does not force the pancreas to release extra insulin. Because of this, it has a low risk of causing dangerously low blood sugar (hypoglycaemia) when taken on its own.

Overall, metformin helps keep blood sugar levels under better control throughout the day while improving the way your body handles glucose.

Adverse Effects

• Vitamin B12 deficiency 
• Lactic Acidosis
• Hypoglycemia
• Hepatic & Renal impairment 
• Diarrhea
• Nausea
• Vomiting
• Flatulence
• Flu like symptoms
• Upper Tespiratory Tract infection 
• Nail disease
• Abdominal distension 

Interactions 

• Corticosteroids– corticosteroid may diminish the hypoglycaemic effect of made for me, so the monitoring is highly necessary
• Carbonic anhydrase inhibitor – carbon can is inventors may enhance the adverse toxic effects of made for metformin
• Diuretics– Thiazide group of Diuretics
• Alcohol
• Luteinizing hormones

Contraindications

• Known Hypersensitivity to Metformin
• In a patient with Acute Chronic Metabolic Acidosis, including Diabetic Keto Acidosis (DKA)
• Renal eGFR<30

Increased Risk for

• Vitamin B12 deficiency
• Lactic acidosis
• Hypoglycaemia 
• Hepatic impairment 
• Hypoxic state

Boxed Warnings

Lactic Acidosis

Although rare, lactic acidosis is the most serious side effect of Metformin. It is a medical emergency that requires immediate treatment and can be life-threatening if not treated promptly.

Lactic acidosis happens when lactic acid builds up in the blood faster than the body can remove it. Early symptoms are often vague and may include:

• Extreme tiredness or weakness
• Muscle pain
• Trouble breathing
• Feeling unusually cold
• Stomach pain, nausea, or vomiting
• Dizziness or light-headedness
• Slow or irregular heartbeat
• The risk is higher in people who:
• Have severe kidney disease
• Are 65 years of age or older
• Take certain medicines, such as carbonic anhydrase inhibitors
• Have severe dehydration, serious infections, liver disease, or conditions that reduce oxygen supply to the body’s tissues

If lactic acidosis is suspected, stop taking metformin immediately and seek emergency medical care. Treatment is usually given in a hospital and may include supportive care and, in severe cases, haemodialysis to remove metformin and excess lactic acid from the blood.

Remember: Lactic acidosis is very rare, and for most people, metformin is a safe and effective medicine when taken as prescribed and with regular monitoring by a healthcare professional.

Adult dose

For type two diabetes mellitus treatment

ORAL, IMMEDIATE RELEASE

The dose of Metformin is different for each person and should be adjusted by a healthcare professional based on blood sugar levels and how well the medicine is tolerated.

Starting dose:

500 mg twice daily with meals, or

850 mg once daily with a meal

Dose adjustment:

The dose can be increased by 500 mg every week, or

Increased by 850 mg every two weeks

The dose is increased gradually to improve blood sugar control and reduce stomach-related side effects such as nausea or diarrhoea.

If needed, patients taking 500 mg twice daily may be switched to 850 mg twice daily after two weeks.

Maximum recommended dose:

2550 mg per day

ORAL, EXTENDED RELEASE

Metformin extended-release (ER) tablets are usually taken once a day with the evening meal.

Starting dose:

500 mg once daily with the evening meal

Dose adjustment:

The dose may be increased by 500 mg every week based on blood sugar control and how well the medicine is tolerated.

Maximum recommended dose:

2000 mg once daily

If blood sugar is still not well controlled with 2000 mg once daily, the doctor may recommend:

1000 mg twice daily, or

Switching to immediate-release metformin if a higher daily dose is needed.

Switching from immediate-release to extended-release:

Patients taking immediate-release metformin can usually switch to the same total daily dose of extended-release metformin, up to a maximum of 2000 mg once daily.

For polycystic Ovary syndrome (PCOS)

Metformin is sometimes used in women with polycystic ovary syndrome (PCOS), especially when insulin resistance is present. However, it is no longer recommended as the primary treatment for infertility caused by a lack of ovulation in women with PCOS, as its effectiveness for this purpose has not been clearly established.

In some women undergoing fertility treatments, such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), doctors may prescribe immediate-release metformin to help reduce the risk of ovarian hyperstimulation syndrome (OHSS).

Typical dose:

• 1,000–2,500 mg per day
• Taken in 2–3 divided doses
• The exact dose is decided by the treating doctor based on the patient’s condition and response to treatment.

Gestational Diabetes

Metformin may be used to help control blood sugar during pregnancy in selected women with gestational diabetes. The dose is adjusted gradually based on blood sugar levels and how well the medicine is tolerated.

Starting dose:

500 mg once daily, or

500 mg twice daily

Dose adjustment:

The dose is gradually increased over 1–2 weeks until the target blood sugar level is achieved.

Maximum recommended dose:

• 2,500 mg per day
• Taken in 2–3 divided doses
• The exact dose and treatment plan should always be determined by the treating obstetrician or healthcare provider.

Paediatric dose

Metformin can be used to treat type 2 diabetes in children aged 10 years and older, as well as adolescents. The dose is started low and increased gradually to improve blood sugar control while reducing stomach related side effects.

Starting dose:

500–1,000 mg once daily, or

500 mg twice daily

Dose adjustment:

The dose may be increased by 500 mg every 1–2 weeks, depending on blood sugar control and how well the medicine is tolerated.

Maximum recommended dose:

1,000 mg twice daily, or

850 mg three times daily

The exact dose should always be decided by the child’s healthcare provider based on their response to treatment.

Dose adjustment

Liver Impairment :

Metformin is generally not recommended in people with significant liver disease. Liver impairment increases the risk of developing lactic acidosis, a rare but serious side effect associated with metformin.

Kidney Impairment

Kidney function should be checked before starting metformin and monitored regularly during treatment.

eGFR <30 mL/min/1.73 m2– Metformin is contraindicated and should not be used.

eGFR 30 to 45 mL/min/1.73 m2– Starting metformin is not recommended.

If eGFR falls <45 mL/min/1.73 m2 during treatment– The healthcare provider should reassess the benefits and risks of continuing metformin. Dose adjustment or discontinuation may be necessary depending on the patient’s condition.

Regular monitoring of kidney function is important to ensure the safe use of metformin.

Pregnancy and Lactation

Metformin is classified as a Pregnancy Category B medication. Although insulin is generally the preferred treatment for diabetes during pregnancy, metformin may be used in selected women when the treating doctor considers it appropriate.

Metformin may be prescribed for:

• Gestational diabetes mellitus (GDM)
• Type 2 diabetes during pregnancy in selected cases

The choice of treatment depends on the mother’s health, blood sugar control, and the doctor’s clinical judgment.

Breastfeeding

Metformin passes into breast milk in small amounts. Available evidence suggests that the amount transferred to the baby is low, but the decision to continue breastfeeding while taking metformin should be made after discussing the benefits and potential risks with a healthcare provider.

The doctor will consider:

• The benefits of breastfeeding for the baby
• The benefits of metformin treatment for the mother
• Any potential risk of the baby being exposed to the medicine through breast milk

General Considerations 

To get the best results from metformin and reduce the risk of side effects, follow these recommendations:

Take metformin with food to reduce stomach upset, nausea, and diarrhoea.

Take the medicine at the same time every day to help maintain consistent blood sugar control.

Avoid drinking excessive amounts of alcohol, as it increases the risk of lactic acidosis.

Immediate-release tablets or oral solution are usually taken in divided doses with meals.

Extended-release oral suspension should be taken with the evening meal. Shake the bottle well for at least 10 seconds before each use and use the supplied dosing cup or measuring device to measure the correct dose.

Extended-release tablets should be taken once daily with the evening meal. Swallow the tablet whole with a full glass of water. Do not crush, chew, or split the tablet.

Metformin should be stopped before or at the time of certain iodinated contrast imaging procedures, especially in people with:
eGFR between 30 and 60 mL/min/1.73 m²

Liver disease

Alcohol use disorder

Heart failure

Those receiving intra-arterial iodinated contrast
Your doctor will advise when it is safe to restart the medicine.

Metformin may need to be temporarily stopped before surgery or any procedure that requires restricted food or fluid intake. This helps reduce the risk of dehydration and kidney problems.

If blood sugar remains uncontrolled after about four weeks of treatment with the maximum tolerated dose of metformin, your doctor may recommend adding another diabetes medicine, such as a sulfonylurea, rather than continuing metformin alone.

Monitoring parameters

Regular monitoring helps ensure that metformin is working effectively and remains safe to use.

Blood Sugar Monitoring

• HbA1c should be checked at least twice a year in people whose blood sugar is well controlled and who have achieved their treatment goals.
• If blood sugar is not well controlled or the treatment plan changes, HbA1c may need to be checked more frequently.
• Fasting blood glucose should be monitored as recommended by your healthcare provider.
• Urine may be tested for glucose and ketones when clinically indicated, especially during illness or when blood sugar is poorly controlled.

Kidney Function

• Kidney function (eGFR) should be checked before starting metformin.
• eGFR should be monitored at least once a year, or more often in people with reduced kidney function or those at higher risk of kidney disease.
• If metformin is temporarily stopped before an iodinated contrast imaging procedure, kidney function should be reassessed 48 hours after the procedure before restarting the medicine.

Vitamin Levels

• Serum vitamin B12 levels should be checked every 2–3 years, especially in people taking metformin for a long time.
• Folate levels may also be monitored if vitamin B12 deficiency is suspected.

Blood Tests

A complete blood count (CBC), including haemoglobin, haematocrit, and other red blood cell parameters, should be checked before starting treatment and then annually.

Read More : https://www.mayoclinic.org/drugs-supplements/metformin-oral-route/description/drg-20067074