Generic Name: Metformin Hydrochloride
Therapeutic Class: Oral Antidiabetic / Biguanide group
Indications
Metformin is the first-line medication for the treatment of type 2 diabetes and several metabolic conditions:
- Type 2 Diabetes Mellitus: Primary treatment to improve glycemic control in adults and children (10 years and older) as monotherapy or in combination with other agents.
- Prediabetes: Used to delay or prevent the onset of Type 2 Diabetes in high-risk individuals.
- Polycystic Ovary Syndrome (PCOS): Used off-label to manage insulin resistance, improve menstrual regularity, and aid in ovulation induction.
- Gestational Diabetes: Sometimes used as an alternative to insulin during pregnancy under specialist supervision.
- Weight Management: Often utilized for its weight-neutral or weight-loss promoting effects in insulin-resistant patients.
Dosage & Administration
Metformin should be taken with meals to minimize gastrointestinal side effects. Dosage is highly individualized.
- Adults (Immediate Release): Starting dose is usually 500 mg twice daily or 850 mg once daily. Dose can be increased by 500 mg weekly up to a maximum of 2550 mg/day.
- Adults (Extended Release): Starting dose is 500 mg to 1000 mg once daily with the evening meal. Maximum dose is 2000 mg/day.
- Pediatrics (10–16 years): Start with 500 mg twice daily. Maximum dose is 2000 mg/day.
- Renal Impairment:
- eGFR 45–60: Continue use, monitor renal function.
- eGFR 30–45: Not recommended to start; if already taking, consider 50% dose reduction.
- eGFR < 30: Contraindicated.
Description & Pharmacokinetics
Metformin is a biguanide antihyperglycemic agent that improves glucose tolerance by lowering both basal and postprandial plasma glucose.
Mechanism of Action: It works through three primary mechanisms: 1. Reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis. 2. Increasing insulin sensitivity in muscle, improving peripheral glucose uptake and utilization. 3. Delaying intestinal glucose absorption. Unlike sulfonylureas, it does not stimulate insulin secretion and therefore does not cause hypoglycemia.
Pharmacokinetics:
Mechanism of Action: It works through three primary mechanisms: 1. Reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis. 2. Increasing insulin sensitivity in muscle, improving peripheral glucose uptake and utilization. 3. Delaying intestinal glucose absorption. Unlike sulfonylureas, it does not stimulate insulin secretion and therefore does not cause hypoglycemia.
Pharmacokinetics:
- Absorption: Bioavailability is approximately 50–60%. Peak plasma levels are reached in 2.5 hours (IR) or 7 hours (ER).
- Distribution: Negligible plasma protein binding. It partitions into erythrocytes.
- Metabolism: Metformin is not metabolized by the liver and does not undergo biliary excretion.
- Excretion: Eliminated unchanged via renal excretion (tubular secretion). The elimination half-life is approximately 6.2 hours in plasma.
Extra Important Information: Usage Insights
- GI Tolerance: Diarrhea and bloating are common at the start. "Start low and go slow" titration is essential for patient compliance.
- Vitamin B12 Deficiency: Long-term use is associated with decreased B12 absorption. Periodic monitoring of B12 levels is recommended.
- Radiology Contrast: Must be discontinued 48 hours before and after procedures involving iodinated contrast to prevent contrast-induced nephropathy.
Side Effects
Most side effects are gastrointestinal and dose-dependent:
- Very Common: Diarrhea, nausea, vomiting, flatulence, and abdominal discomfort.
- Common: Metallic taste in the mouth and anorexia.
- Rare but Serious: Lactic Acidosis (characterized by malaise, respiratory distress, and abdominal pain). This is a medical emergency.
- Skin: Very rare cases of erythema or pruritus.
Pregnancy & Lactation
- Pregnancy: Category B. It is increasingly used for gestational diabetes and PCOS-related pregnancy. It crosses the placenta, but studies have not shown increased risk of major malformations.
- Lactation: Metformin is excreted into human milk. While infant exposure is low, it should be used with caution, monitoring the infant's growth and blood glucose.
Precautions & Interactions
- Lactic Acidosis Risk: Increased in patients with renal impairment, heavy alcohol consumption, or congestive heart failure.
- Cimetidine & Dolutegravir: These drugs can increase metformin levels by competing for renal tubular transport.
- Alcohol: Potentiates the effect of metformin on lactate metabolism; avoid excessive intake.
- Hypoglycemia: Does not occur with metformin alone but risk increases when combined with Insulin or Sulfonylureas.
Storage
Store at 20°C to 25°C. Protect from light and moisture. Keep tablets in a tightly closed container. Keep out of reach of children.
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