Glucophage, with the active ingredient metformin hydrochloride, stands as a first-line pharmacological therapy and a cornerstone in the global management of Type 2 Diabetes Mellitus (T2DM). It is an oral antihyperglycemic agent belonging to the biguanide class, renowned for its efficacy, well-established safety profile, and multifaceted mechanism of action. This medication works primarily by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike many other diabetic medications, it is not associated with weight gain and carries a low risk of hypoglycemia when used as monotherapy, making it a fundamental and often initial choice for clinicians worldwide to achieve and maintain glycemic control.

Features

• Active Ingredient: Metformin Hydrochloride.
• Pharmacologic Class: Biguanide antihyperglycemic agent.
• Available Formulations: Immediate-release tablets (500 mg, 850 mg, 1000 mg) and extended-release tablets (500 mg, 750 mg).
• Primary Mechanism of Action: Reduces hepatic gluconeogenesis and enhances peripheral insulin sensitivity.
• Administration: Oral route.
• Bioavailability: Absolute bioavailability of a 500 mg tablet is approximately 50-60%.

Benefits

• Establishes Foundational Glycemic Control: Effectively lowers both fasting and postprandial blood glucose levels and reduces HbA1c, a key long-term marker of glycemic health.
• Cardiovascular Risk Profile: Associated with a neutral or potentially beneficial effect on cardiovascular outcomes, a critical consideration in T2DM patients.
• Weight-Neutral Management: Unlike sulfonylureas or insulin, metformin therapy is typically not associated with weight gain and may support modest weight loss in some patients.
• Low Hypoglycemia Risk: As monotherapy, it does not cause hypoglycemia because its action is not dependent on stimulating insulin secretion from pancreatic beta cells.
• Potential Pleiotropic Effects: Research suggests possible benefits beyond glucose control, including improved lipid profiles and other metabolic parameters.

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 universally recognized as the initial pharmacological intervention upon diagnosis. It is used both as monotherapy and in combination with other oral antihyperglycemic agents (e.g., DPP-4 inhibitors, SGLT2 inhibitors) or with insulin when glycemic targets are not achieved with metformin alone. Its use is also well-established in the management of polycystic ovary syndrome (PCOS) to address insulin resistance and support ovulation induction, though this is an off-label application.

Dosage and direction

Dosage must be individualized based on efficacy and tolerability, under the direct supervision of a healthcare provider.

• Immediate-Release Tablets: The usual starting dose is 500 mg twice daily or 850 mg once daily, taken with meals. Dosage may be increased gradually, typically at weekly intervals, to minimize gastrointestinal adverse effects. The maximum recommended daily dose is 2550 mg administered in divided doses. A common effective dose is 2000 mg per day.
• Extended-Release Tablets: The usual starting dose is 500 mg once daily with the evening meal. Dosage can be increased by 500 mg weekly, up to a maximum of 2000 mg taken once daily with the evening meal. Alternatively, the total daily dose may be divided and given twice daily with meals.
• Administration: Tablets must be swallowed whole and never crushed or chewed. Immediate-release formulations are taken with meals to reduce GI upset. Extended-release tablets must be taken whole, once daily with the evening meal.
• Renal Dosing: Dosage requires adjustment based on renal function, as estimated by glomerular filtration rate (eGFR). It is contraindicated in patients with an eGFR below 30 mL/min/1.73m². Use is not recommended for initiating therapy in patients with an eGFR between 30-45 mL/min/1.73m².

Precautions

• Lactic Acidosis: A rare but serious metabolic complication that can occur due to metformin accumulation. Risk factors include renal impairment, concomitant use of certain drugs (that can affect renal function or metabolic state), age >65 years, radiographic contrast procedures, hypoxic states (e.g., congestive heart failure, acute CHF exacerbation), excessive alcohol intake, and hepatic impairment. Therapy should be temporarily discontinued prior to any intravascular iodinated contrast imaging procedure and withheld for 48 hours post-procedure, with renal function re-evaluated before restarting.
• Vitamin B12 Deficiency: Long-term use of metformin has been associated with decreased Vitamin B12 absorption, which may lead to hematological or neurological manifestations. Periodic monitoring of hematological parameters is advised.
• Surgery: Glucophage should be temporarily discontinued at the time of, or prior to, surgical procedures (except minor procedures not associated with restricted intake of food and fluids) and withheld for 48 hours post-operation until renal function is confirmed to be normal and oral intake has resumed.
• Hepatic Disease: Use with caution in patients with hepatic disease, as impaired liver function is a risk factor for lactic acidosis.

Contraindications

• Severe renal impairment (eGFR < 30 mL/min/1.73m²).
• Known hypersensitivity to metformin hydrochloride or any excipient in the formulation.
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
• Temporary withholding for 48 hours following procedures using iodinated contrast media.
• Conditions predisposing to renal hypoperfusion or hypoxia (e.g., decompensated heart failure, septicemia, acute 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%): Taste disturbance (metallic taste), decreased Vitamin B12 levels.
• Rare but Serious: Lactic acidosis (symptoms include malaise, myalgia, respiratory distress, somnolence, abdominal pain). Hypoglycemia (when used concomitantly with other glucose-lowering agents like insulin or sulfonylureas).

Drug interaction

Concomitant use requires careful monitoring and potential dosage adjustment.

• Drugs that Impair Renal Function: Coadministration with drugs that may affect renal function (e.g., diuretics, NSAIDs, ACE inhibitors) or compete for renal tubular secretion may 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 should be avoided or consumed very cautiously.
• Cationic Drugs: Drugs that are eliminated by renal tubular secretion (e.g., cimetidine, digoxin, amiloride, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin) may increase metformin plasma levels by competing for common renal tubular transport systems.
• Other Antidiabetic Agents: When used in combination with insulin or insulin secretagogues (e.g., sulfonylureas), the risk of hypoglycemia is increased.

Missed dose

If a dose is missed, it should be taken as soon as the patient remembers, unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. The patient should not take a double dose to make up for a missed one.

Overdose

Hypoglycemia has not been seen with metformin overdose when used as monotherapy; however, lactic acidosis remains a primary concern. Overdose, or accumulation due to contraindicated conditions, may lead to the onset of lactic acidosis, which is a medical emergency requiring immediate hospitalization. Treatment is supportive and directed at correcting acidosis and removing metformin via hemodialysis, which corrects acidosis and removes metformin efficiently.

Storage

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
• Keep the bottle 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 purposes only and 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. The information provided is based on the typical properties of the drug and may not cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects.

Reviews

• Clinical Endocrine Practice: “Metformin remains the undisputed first-line therapy for Type 2 Diabetes. Its efficacy in reducing HbA1c by 1-2%, its favorable effects on weight and lipid profile, and its extensive real-world evidence base make it an indispensable tool. The extended-release formulation has significantly improved GI tolerability, enhancing patient adherence.”
• Journal of the American Board of Family Medicine: “The benefits of metformin extend beyond glycemic control. Its role in cardiovascular risk modulation, even if modest, and its cost-effectiveness solidify its position as the foundational agent in most T2DM treatment algorithms. Vigilance for rare side effects like lactic acidosis is paramount but should not overshadow its overwhelming benefit-to-risk ratio.”
• Patient Feedback (Aggregated Theme): Many patients report initial gastrointestinal discomfort that often subsides after the first few weeks of therapy. Those who persist consistently report satisfactory glucose control without weight gain. A common positive note is the convenience of the once-daily extended-release version.