Metformin

Metformin hydrochloride is a first-line, biguanide-class oral antihyperglycemic agent, widely recognized as the foundational pharmacological therapy for the management of type 2 diabetes mellitus (T2DM). Its primary mechanism of action involves decreasing hepatic glucose production (gluconeogenesis) and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike many other antidiabetic agents, metformin is not associated with weight gain and carries a low risk of hypoglycemia when used as monotherapy, making it a preferred initial choice for clinicians worldwide. Its well-established efficacy, favorable safety profile, and extensive clinical history position it as an indispensable tool in modern endocrinology.

Features

• Active Ingredient: Metformin Hydrochloride.
• Drug Class: Biguanide antihyperglycemic.
• Available Formulations: Immediate-release (IR) tablets (500 mg, 850 mg, 1000 mg), extended-release (XR or ER) tablets (500 mg, 750 mg, 1000 mg), and oral solution.
• Mechanism of Action: Primarily suppresses hepatic gluconeogenesis; secondarily enhances insulin-mediated glucose utilization in peripheral tissues (muscle and adipose).
• Pharmacokinetics: Not metabolized by the liver; excreted unchanged in the urine via tubular secretion. The extended-release formulation is designed for once-daily dosing with a slower absorption profile.
• Prescription Status: Available by prescription only.

Benefits

• Effective Glycemic Control: Significantly reduces both fasting and postprandial blood glucose levels and lowers HbA1c, a key long-term marker of glycemic control.
• Cardiovascular Protection: Associated with a neutral or beneficial effect on cardiovascular outcomes, including potential reductions in major adverse cardiovascular events in certain patient populations.
• Weight-Neutral or Weight-Loss Promoting: Unlike sulfonylureas or insulin, metformin is typically not associated with weight gain and may facilitate modest weight loss, which is beneficial in managing T2DM.
• Low Risk of Hypoglycemia: As monotherapy, it does not stimulate insulin secretion and therefore carries a very low risk of causing dangerously low blood sugar.
• Potential Pleiotropic Effects: Ongoing research suggests possible benefits beyond glucose control, including positive effects on lipid profiles and reduced cancer risk, though these are not yet primary indications for use.
• Cost-Effective: As a widely available generic medication, it is a highly cost-effective option for long-term management.

Common use

Metformin is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. It is used as first-line monotherapy and is also commonly combined with other oral antidiabetic agents (e.g., DPP-4 inhibitors, SGLT2 inhibitors) or injectable therapies (e.g., insulin, GLP-1 receptor agonists) when additional glycemic control is required. It is also used off-label for the management of polycystic ovary syndrome (PCOS) to address insulin resistance and regulate menstrual cycles.

Dosage and direction

Dosage must be individualized based on efficacy and tolerance, with the goal of using the lowest effective dose.

• Adults (Immediate-Release): The usual starting dose is 500 mg orally twice daily or 850 mg once daily with meals. Dosage may be increased gradually in increments of 500 mg weekly or 850 mg every two weeks, based on glycemic control. The maximum recommended daily dose is 2550 mg administered in divided doses. A common effective dose is 2000 mg per day (e.g., 1000 mg twice daily).
• Adults (Extended-Release): The usual starting dose is 500 mg orally once daily with the evening meal. Dose may be increased by 500 mg weekly, up to a maximum of 2000 mg once daily. Tablets must be swallowed whole and never crushed or chewed.
• Pediatric Patients (10-16 years): The usual starting dose is 500 mg twice daily. Dose may be increased by 500 mg weekly up to a maximum of 2000 mg per day.
• Administration: Always take with food to minimize gastrointestinal upset. Consistent timing of doses is important for stable glycemic control.

Precautions

• Lactic Acidosis: Although rare, lactic acidosis is a serious, life-threatening metabolic complication. Risk is increased by conditions that can predispose to hypoperfusion and hypoxia (e.g., congestive heart failure requiring pharmacologic management, acute or chronic metabolic acidosis, renal impairment, excessive alcohol intake).
• Vitamin B12 Deficiency: Long-term use of metformin has been associated with decreased vitamin B12 absorption and lower serum levels. Periodic monitoring of hematological parameters is advised.
• Surgical Procedures: Metformin should be temporarily discontinued at the time of, or prior to, any surgical procedure or radiologic study involving intravascular iodinated contrast materials and withheld for 48 hours after the procedure, only to be restarted after renal function has been re-evaluated and found to be normal.
• Hepatic Impairment: Use with caution in patients with hepatic disease, as impaired liver function can significantly increase the risk of lactic acidosis.
• Alcohol Intake: Patients should be advised to avoid excessive alcohol intake, either acute or chronic, while taking metformin, as alcohol can potentiate the effect of metformin on lactate metabolism.

Contraindications

Metformin is contraindicated in patients with:

• Severe renal impairment (eGFR below 30 mL/min/1.73m²) or renal disease.
• Known hypersensitivity to metformin hydrochloride or any ingredient in the formulation.
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis (DKA), with or without coma.
• Any condition that may predispose to renal hypoperfusion or hypoxia, such as cardiovascular collapse (shock), acute congestive heart failure, or recent myocardial infarction.

Possible side effect

The most common adverse reactions are gastrointestinal in nature and often transient.

• Very Common (>10%): Diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion.
• Common (1-10%): Unpleasant metallic taste, asthenia (lack of energy).
• Rare but Serious:
  • Lactic acidosis (symptoms include malaise, myalgia, respiratory distress, somnolence, abdominal pain).
  • Vitamin B12 deficiency (manifesting as megaloblastic anemia or peripheral neuropathy).
  • Hepatitis, skin reactions such as urticaria.

Drug interaction

Concomitant use of certain drugs may require closer monitoring or dose adjustment.

• Drugs that Impair Renal Function: Coadministration with drugs that may affect renal function (e.g., diuretics, NSAIDs, ACE inhibitors) or compete for common tubular secretory systems (e.g., cimetidine, digoxin) may increase the risk of lactic acidosis and metformin accumulation.
• Iodinated Contrast Media: Can cause acute renal failure, increasing the risk of metformin-associated lactic acidosis. Requires temporary discontinuation.
• Alcohol: Potentiates the effect of metformin on lactate metabolism and increases the risk of lactic acidosis.
• Other Hypoglycemic Agents: When used in combination with insulin or insulin secretagogues (e.g., sulfonylureas), the risk of hypoglycemia may be increased.

Missed dose

If a dose is missed, it should be taken as soon as remembered that day. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not take a double dose to make up for a missed one. Maintaining a regular dosing schedule is important for optimal glycemic control.

Overdose

Hypoglycemia has not been seen with metformin overdose when used as monotherapy; however, lactic acidosis remains the primary concern. Overdose, or accumulation due to contraindicated conditions, can lead to lactic acidosis, which is a medical emergency requiring immediate hospitalization. Symptoms of lactic acidosis are non-specific and include vomiting, diarrhea, abdominal pain, malaise, myalgia, and profound lethargy. Treatment is supportive and involves prompt hemodialysis, which corrects acidosis and removes accumulated metformin.

Storage

• Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).
• Keep the container tightly closed to protect from moisture and light.
• Keep out of reach of children and pets.
• Do not use after the expiration date printed on the container.
• Properly dispose of any unused or expired medication.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting, stopping, or changing any prescribed part of your care plan. Never disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

• Clinical Endocrine Review: “Metformin remains the gold standard for initial pharmacotherapy in type 2 diabetes. Its efficacy, safety profile, cardiovascular neutrality, and cost-effectiveness are unmatched. Decades of real-world use have solidified its role as the cornerstone of management.”
• Patient Feedback (Aggregated): Many patients report significant improvements in their HbA1c levels and appreciate the lack of weight gain. The initial gastrointestinal side effects are a common point of discussion, though most patients report that these symptoms subside with continued use and taking the medication with food. A minority of long-term users report the need for B12 supplementation.