Metformin

Antidiabetic Drug

Drug class: Biguanide

Metformin (GLUCOPHAGE)（中文： 甲福明, 二甲雙胍）

Pronunciation

Metformin 250mg

Metformin 500mg

Common Strengths of Metformin Tablet

Metformin tablets are available in the following strengths:

• Immediate-release: 250 mg, 500 mg, 850 mg, and 1000 mg.
• Extended-release: 500 mg, 750 mg, and 1000 mg.

Drug Trade Names of Metformin Tablet

Glucophage is the trade name for Metformin:

• Glucophage Tablet 500mg, 850mg, 1000mg
• Glucophage XR prolonged release tablet 500mg, 750mg, 1000mg.

It is also sold under various brand names when combined with other antidiabetic medications, such as:

• ACTOSMET 15MG/850MG TABLET (Pioglitazone HCL 15mg + Metformin HCL 850mg)
• GALVUS MET TABLET 50/1000MG (Vildagliptin 50mg + Metformin HCL 1000mg)
• GALVUS MET TABLET 50/500MG (Vildagliptin 50mg + Metformin HCL 500mg)
• GALVUS MET TABLET 50/850MG (Vildagliptin 50mg + Metformin HCL 850mg)
• JANUMET TABLET 50/1000MG (Sitagliptin phosphate 50mg + Metformin HCL 1000mg)
• JANUMET TABLET 50/500MG (Sitagliptin phosphate 50mg + Metformin HCL 500mg)
• JARDIANCE DUO TABLET 12.5MG/500MG (Empagliflozin 12.5mg + Metformin HCL 500mg)
• JARDIANCE DUO TABLET 12.5MG/850MG (Empagliflozin 12.5mg + Metformin HCL 850mg)
• JARDIANCE DUO TABLET 12.5MG/1000MG (Empagliflozin 12.5mg + Metformin HCL 1000mg)
• JARDIANCE DUO TABLET 5MG/500MG (Empagliflozin 5mg + Metformin HCL 500mg)
• JARDIANCE DUO TABLET 5MG/850MG (Empagliflozin 5mg + Metformin HCL 850mg)
• KOMBIGLYZE XR TABLET 2.5MG/1000MG (Saxagliptin HCL 2.5mg + Metformin HCL 1000mg)
• KOMBIGLYZE XR TABLET 5MG/1000MG (Saxagliptin HCL 5mg + Metformin HCL 1000mg)
• KOMBIGLYZE XR TABLET 5MG/500MG (Saxagliptin HCL 5mg + Metformin HCL 500mg)
• TRAJENTA DUO TABLET 2.5/1000MG (Linagliptin 2.5mg + Metformin HCL 1000mg)
• TRAJENTA DUO TABLET 2.5/850 (Linagliptin 2.5mg + Metformin HCL 850mg)
• TRAJENTA DUO TABLET 2.5/500MG (Linagliptin 2.5mg + Metformin HCL 500mg)
• XIGDUO XR EXTENDED-RELEASE TABLET 10MG/1000MG (Dapagliflozin propanediol 10mg + Metformin HCL 1000mg)
• XIGDUO XR EXTENDED-RELEASE TABLET 10MG/500MG (Dapagliflozin propanediol 10mg + Metformin HCL 500mg)
• XIGDUO XR EXTENDED-RELEASE TABLET 5MG/1000MG (Dapagliflozin propanediol 5mg + Metformin HCL 1000mg)

Drug Usage

To treat type 2 diabetes mellitus.

Mechanism of Action

Metformin primarily works by:

• Decreasing hepatic glucose production (gluconeogenesis).
• Increasing insulin sensitivity and peripheral glucose uptake.
• Decreasing intestinal absorption of glucose.

Metformin is often used in combination with other diabetes medications due to its complementary mechanisms of action.

While metformin remains a cornerstone of type 2 diabetes treatment due to its efficacy, safety, and cost-effectiveness, newer drug classes offer additional benefits in certain patient populations. The choice of medication should be tailored to individual patient needs and characteristics.

Route of Administration

Metformin is administered orally in the form of tablets or liquid solution.

Dosages

Normal People

• Initial dose: 500 mg once or twice daily with meals.
• Maintenance dose: Gradually increased to 2000 mg per day in divided doses.
• Maximum dose: 3000 mg daily.

Hypertension and Heart Failure

No specific dosage adjustments are recommended solely for hypertension or heart failure, but caution is advised due to the risk of lactic acidosis.

Diabetic Kidney Disease

• eGFR ≥ 45 mL/min/1.73 m²: Standard dosing.
• eGFR 30-44 mL/min/1.73 m²: Maximum 1000 mg per day.
• eGFR < 30 mL/min/1.73 m²: Contraindicated.

Side Effects

Frequency	Adverse reactions
Common	Gastrointestinal issues: Diarrhea, nausea, vomiting, abdominal pain
	Taste disturbance
	Loss of appetite
Uncommon	Skin reactions: Erythema, pruritus, urticaria
	Lactic acidosis
	Vitamin B12 deficiency
	Hepatitis
	Liver function abnormalities

Pharmacokinetics

• Absorption
  • Bioavailability is 50-60%. Metformin reaches maximum plasma concentration in 1-3 hours after taking immediate-release tablets. For extended-release formulations, peak plasma levels are reached in 4-8 hours.
• Metabolism
  • Not metabolized by the liver.
• Excretion
  • Primarily excreted unchanged in urine.
• Half-life
  • 4 - 8.7 hours

Drug Precautions

Pregnancy

Generally considered safe, but should be used under medical supervision.

Breastfeeding

Metformin is excreted in breast milk, but the risk to the infant is considered low.

Children and Elderly

• Not recommended for children under 10 years.
• Use with caution in the elderly due to the potential for decreased renal function.

Renal Impairment

• Contraindicated in patients with eGFR < 30 mL/min/1.73 m².
• Dose adjustments required for eGFR 30-44 mL/min/1.73 m².

Monitoring Requirements

• Regularly monitor renal function, blood glucose, and vitamin B12 levels.
• Monitor for signs of lactic acidosis, especially in patients with renal impairment.

The key symptoms of metformin-associated lactic acidosis (MALA) include:

Gastrointestinal	Nausea and vomiting
	Abdominal pain
	Diarrhoea
Neurological	Confusion
	Lethargy
Resoiratory	Rapid breathing
	Difficulty breathing
Cardiovascular	Hypotension
	Rapid heart rate
General	Extreme tiredness
	Feeling cold, especially in arms and legs
Other	Dizziness
	Lighteadedness

It is important to note that these symptoms can be nonspecific and may overlap with other conditions. MALA is a medical emergency that requires immediate treatment.

Drug Interaction

• Cimetidine: This antacid can increase metformin levels in the blood by inhibiting its elimination.
• Diuretics, especially loop diuretics eg Frusemide: Can increase the risk of lactic acidosis
• Corticosteroids: May increase blood glucose levels, potentially reducing metformin's effectiveness
• NSAIDs: Long-term use may increase the risk of lactic acidosis, especially in those with reduced kidney function

FAQ

How Should I Take the Tablet?

• Take with meals to reduce gastrointestinal side effects.
• Swallow whole; do not crush or chew extended-release tablets.

What Should I Avoid While Taking?

• Avoid excessive alcohol consumption due to increased risk of lactic acidosis.
• Avoid skipping meals to prevent hypoglycemia.

What Happens if I Miss a Dose?

• Take the missed dose as soon as you remember unless it is almost time for the next dose.
• Do not double the dose to make up for the missed one.