Glucophage, with the active ingredient metformin hydrochloride, is a foundational oral antihyperglycemic agent specifically designed for the management of type 2 diabetes mellitus. It functions primarily by decreasing hepatic glucose production and intestinal absorption of glucose, while improving insulin sensitivity by increasing peripheral glucose uptake and utilization. This medication is a cornerstone therapy, often prescribed as the initial pharmacological intervention upon diagnosis, and can be used concomitantly with other antidiabetic agents, including insulin, for synergistic glycemic control. Its well-established efficacy and safety profile have made it a gold standard in diabetes care protocols worldwide.

Features

• Active Ingredient: Metformin Hydrochloride.
• Available in immediate-release (IR) tablets (500 mg, 850 mg, 1000 mg) and extended-release (XR) formulations.
• Mechanism of Action: Biguanide class; reduces hepatic gluconeogenesis and enhances insulin-mediated glucose disposal.
• Bioavailability: Approximately 50-60% under fasting conditions.
• Protein Binding: Negligible.
• Elimination Half-Life: Approximately 6.5 hours.
• Excretion: Primarily via the kidneys in an unchanged form.
• Tmax (Time to peak plasma concentration): IR: 2-3 hours; XR: 7 hours.

Benefits

• Achieves significant and sustained reductions in both fasting and postprandial plasma glucose levels, as measured by HbA1c.
• Promotes modest weight loss or weight neutrality, a distinct advantage over many other antidiabetic medications that can cause weight gain.
• Improves lipid profile by potentially lowering triglycerides and LDL cholesterol levels.
• Demonstrates a very low risk of causing hypoglycemia when used as monotherapy.
• May offer cardiovascular protective benefits, as evidenced by long-term outcome studies.
• Cost-effective and widely accessible due to its availability as a generic medication.

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 the preferred first-line pharmacological agent upon diagnosis. It is also used off-label for the management of conditions like Polycystic Ovary Syndrome (PCOS) to address insulin resistance and support ovulation induction.

Dosage and direction

Dosage must be individualized based on efficacy and tolerability, with a gradual escalation to minimize gastrointestinal adverse effects.

• Initial Dose: The usual starting dose for adults is 500 mg orally twice daily or 850 mg once daily with meals. For the extended-release formulation, the initial dose is 500 mg orally once daily with the evening meal.
• Dosage Titration: Dosage may be increased in increments of 500 mg weekly or 850 mg every two weeks.
• Maintenance Dose: The effective dosage range is typically 1500 mg to 2000 mg per day. The maximum recommended daily dose is 2550 mg for the immediate-release and 2000 mg for the extended-release formulation.
• Administration: Immediate-release tablets should be divided and taken two to three times daily with meals. Extended-release tablets must be swallowed whole and never crushed or chewed, taken once daily with the evening meal.
• Pediatric Use (ages 10-16): The starting dose is 500 mg twice daily, with titration up to a maximum of 2000 mg per day.

Precautions

• Lactic Acidosis: A rare but serious metabolic complication. Risk is increased by conditions such as renal impairment, congestive heart failure requiring pharmacologic management, advanced age, hepatic impairment, acute congestive heart failure, acute myocardial infarction, and other conditions predisposing to hypoperfusion and hypoxemia.
• Vitamin B12 Deficiency: Long-term use of metformin has been associated with decreased Vitamin B12 absorption. Periodic monitoring of hematological parameters is advised.
• Surgical Procedures: Glucophage should be temporarily discontinued at the time of, or prior to, any surgical procedure and withheld for 48 hours after the procedure until renal function is confirmed to be normal and the patient is eating normally.
• Renal Function: Renal function (e.g., serum creatinine) must be assessed before initiation of therapy and regularly thereafter.
• Hepatic Disease: Avoid use in patients with clinical or laboratory evidence of hepatic disease.

Contraindications

• 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, with or without coma.
• Temporary contraindication in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, as this can alter renal function. Glucophage should be discontinued at the time of, or prior to, the procedure and withheld for 48 hours afterwards.

Possible side effect

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

• Very Common (>10%): Diarrhea, nausea/vomiting, flatulence, abdominal discomfort.
• Common (1-10%): Asthenia, indigestion, headache, taste disturbance.
• Uncommon (0.1-1%): Vitamin B12 deficiency (see Precautions).
• Rare (<0.1%): Lactic acidosis (see Precautions), hepatitis, skin reactions such as urticaria.
• Very Rare: Erythema, pruritus.

Drug interaction

Concomitant use requires careful monitoring and potential dosage adjustment.

• Drugs that impair renal function (e.g., NSAIDs, certain antihypertensives) can increase the risk of metformin accumulation and lactic acidosis.
• Alcohol: Potentiates the effect of metformin on lactate metabolism and increases the risk of lactic acidosis. Alcohol consumption should be avoided.
• Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin) that are eliminated by renal tubular secretion could potentially increase metformin exposure by competing for common renal tubular transport systems.
• Glucocorticoids, diuretics, and sympathomimetics may produce hyperglycemia and may require dosage adjustment of Glucophage.

Missed dose

If a dose is missed, it should be taken as soon as the patient remembers. 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 the missed one. Maintaining a regular dosing schedule is important for optimal glycemic control.

Overdose

Overdose of Glucophage has occurred, including intentional overdose and ingestion of very large amounts. Hypoglycemia has been reported in such cases, though metformin alone does not typically cause hypoglycemia. Lactic acidosis is the primary concern in overdose situations and is a medical emergency. Hemodialysis is effective for removing accumulated metformin and correcting acidosis; therefore, prompt hemodialysis is recommended.

Storage

• Store at room temperature between 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 packaging.

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 any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

“Glucophage has been the bedrock of my type 2 diabetes management for over a decade. After initial GI adjustment, it has been exceptionally well-tolerated. My HbA1c has remained consistently within target range, and I appreciate that it doesn’t cause the weight gain associated with some other medications. Its efficacy and safety profile are well-documented, giving me and my endocrinologist great confidence in its long-term use.” – M.B., Patient for 12 years.

“As a practicing endocrinologist, metformin remains my first-line go-to therapy for newly diagnosed type 2 diabetes. Its dual action on hepatic glucose output and peripheral sensitivity, combined with its cardiovascular neutrality (or possible benefit) and favorable side effect profile after the initial period, makes it an unparalleled agent. The extended-release formulation has significantly improved patient compliance and tolerability.” – Dr. A. Sharma, MD, Endocrinology.