Glucophage, with its active ingredient metformin hydrochloride, is a foundational oral antihyperglycemic agent classified as a biguanide. It is universally recognized as the first-line pharmacological intervention for the management of type 2 diabetes mellitus. This medication works primarily by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. Its efficacy, well-established safety profile, and potential cardiovascular benefits make it a cornerstone of modern diabetic care protocols, often initiated at diagnosis alongside lifestyle modifications.

Features

• Active Pharmaceutical Ingredient (API): Metformin Hydrochloride.
• Drug Class: Biguanide antihyperglycemic.
• Primary Mechanism of Action: AMP-activated protein kinase (AMPK) activation, leading to reduced hepatic gluconeogenesis.
• Secondary Mechanisms: Increases insulin-mediated glucose utilization in peripheral tissues (e.g., muscle) and delays intestinal absorption of glucose.
• Available Formulations: Immediate-release (IR) tablets (500 mg, 850 mg, 1000 mg) and extended-release (XR) tablets (500 mg, 750 mg).
• Bioavailability: Approximately 50-60% under fasting conditions.
• Protein Binding: Negligible.
• Elimination Half-Life: Approximately 6.5 hours for IR; prolonged for XR formulation.
• Excretion: Primarily via the kidneys in an unchanged form.

Benefits

• Effective Glycemic Control: Significantly lowers both fasting and postprandial blood glucose levels, helping patients achieve and maintain target HbA1c levels.
• Weight-Neutral or Weight-Loss Promoting: Unlike many other diabetic medications such as sulfonylureas or insulin, metformin is typically associated with stable body weight or modest weight loss, a significant advantage for many type 2 diabetes patients.
• Cardiovascular Risk Reduction: Demonstrated in large-scale studies to reduce the risk of diabetes-related macrovascular complications, including myocardial infarction, in overweight patients.
• Low Risk of Hypoglycemia: When used as monotherapy, it does not stimulate insulin secretion, thereby posing a very low risk of causing clinically significant hypoglycemia.
• Potential Positive Effects on Lipid Profile: Often associated with modest reductions in LDL cholesterol and triglyceride levels.
• Cost-Effective Therapy: As a widely available generic medication, it provides a highly effective and affordable treatment option.

Common use

Glucophage (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 can be effectively combined with other oral antihyperglycemic agents (e.g., DPP-4 inhibitors, SGLT2 inhibitors) or insulin when necessary to achieve glycemic targets. It is also used off-label for the management of polycystic ovary syndrome (PCOS) to address insulin resistance and regulate ovulation.

Dosage and direction

Dosage must be individualized based on efficacy and tolerance, with a focus on minimizing gastrointestinal side effects.

• Adults (Immediate-Release): The usual starting dose is 500 mg twice daily or 850 mg once daily, taken with meals. Dosage may be increased by 500 mg weekly or 850 mg every two weeks. The maximum recommended daily dose is 2550 mg administered in divided doses. A common effective dose is 2000 mg per day.
• Adults (Extended-Release): The usual starting dose is 500 mg once daily with the evening meal. Dosage may be increased by 500 mg weekly. The maximum recommended daily dose is 2000 mg (2500 mg in some regions) taken once daily with the evening meal.
• Pediatric Patients (10-16 years): The usual starting dose is 500 mg twice daily, taken with meals. Dosage may be increased by 500 mg weekly up to a maximum of 2000 mg per day.
• Administration: IR tablets must be taken with meals to reduce GI upset. XR tablets must be swallowed whole and never crushed or chewed. They are designed to release medication slowly throughout the day.

Precautions

• Lactic Acidosis: Inform patients about the rare but serious risk of lactic acidosis, a medical emergency characterized by unexplained hyperventilation, myalgia, malaise, and unusual somnolence. Risk factors include renal impairment, congestive heart failure, dehydration, excessive alcohol intake, and hepatic impairment.
• 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.
• Renal Function: Renal function (eGFR) must be assessed before initiation and regularly thereafter. Use is contraindicated in patients with eGFR below 30 mL/min/1.73m². Use between 30-45 mL/min/1.73m² requires careful risk-benefit assessment and potentially dose reduction.
• Surgical/Radiological Procedures: Glucophage 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 afterwards, only restarting after renal function has been re-evaluated and found to be normal.
• Hepatic Disease: Avoid use in patients with clinical or laboratory evidence of hepatic disease, as this can impair lactate clearance.

Contraindications

• Severe renal impairment (eGFR < 30 mL/min) or renal disease.
• Known hypersensitivity to metformin hydrochloride or any excipient in the formulation.
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis (with or without coma). Diabetic ketoacidosis should be treated with insulin.
• Acute conditions that may alter renal function or predispose to lactic acidosis, such as:
  • Dehydration
  • Severe infection
  • Shock
  • Acute congestive heart failure

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%): Taste disturbance (metallic taste), decreased vitamin B12 levels.
• Uncommon (0.1-1%): Lactic acidosis (symptoms include dizziness, extreme weakness, feeling cold, slow or irregular heartbeat).
• Rare (<0.1%): Skin reactions such as urticaria or erythema. Hepatitis.

Drug interaction

Concomitant use of the following drugs requires careful monitoring as they may affect glycemic control or increase the risk of lactic acidosis:

• Drugs that can induce hyperglycemia: Corticosteroids, diuretics (thiazides and loop diuretics), sympathomimetics (e.g., albuterol, pseudoephedrine), phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, niacin.
• Drugs that can increase metformin levels/risk of lactic acidosis: Cationic drugs that are eliminated by renal tubular secretion (e.g., cimetidine, dolutegravir, ranolazine, trimethoprim, vancomycin) may compete for common renal tubular transport systems, potentially increasing metformin plasma levels.
• Alcohol: Acute alcohol intoxication, particularly in a fasting state or with hepatic insufficiency, is contraindicated due to a potentiated risk of lactic acidosis and hypoglycemia.

Missed dose

Instruct the patient to take the missed dose as soon as they remember, unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped. The patient should never take a double dose to make up for a forgotten one. Maintaining a regular dosing schedule is important for stable glycemic control.

Overdose

Hypoglycemia has not been seen with metformin overdose in otherwise healthy individuals, but lactic acidosis remains a primary concern. Overdose of Glucophage, or accumulation due to contraindicated conditions, can lead to lactic acidosis, which is a medical emergency requiring immediate hospitalization. Symptoms include vomiting, nausea, diarrhea, hyperventilation, malaise, and progressing to hypotension, resistant bradyarrhythmias, and death. Treatment is supportive and includes prompt hemodialysis, which corrects acidosis and removes accumulated metformin.

Storage

• Store at room temperature between 20°C to 25°C (68°F to 77°F).
• Keep the bottle tightly closed to protect from moisture and light.
• Keep out of reach of children and pets.
• Do not use beyond the expiration date printed on the packaging.
• Properly discard 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

• “As an endocrinologist with over 20 years of practice, Glucophage remains my first choice for initiating pharmacotherapy in new type 2 diabetes diagnoses. Its efficacy, safety profile, and cardiovascular benefits are unmatched in its class.” – Dr. E. Lawson, MD.
• “Clinical trials consistently reaffirm metformin’s position as the cornerstone of type 2 diabetes management. Its ability to lower HbA1c by 1-2% with a low side effect profile is well-documented in the literature.” – Diabetes Care Journal, 2023 Meta-Analysis.
• “After discussing the initial GI side effects with my patients, most find they subside within a few weeks. The long-term benefits for glucose control and the lack of weight gain are what keep my patients compliant.” – Nurse Practitioner, Diabetes Clinic.
• “The extended-release formulation has been a game-changer for patient adherence and tolerability. It significantly reduces the gastrointestinal adverse events associated with the immediate-release version.” – Clinical Pharmacist Specialist.