Medication Guide for Metformin

Brand Names

Metformin is marketed under various brand names, including Glucophage, Glucophage XR, Fortamet, Glumetza, and Riomet.

Medication Classification

Metformin belongs to the class of medications known as biguanides, which exert their effects primarily by decreasing glucose production in the liver and improving insulin sensitivity in peripheral tissues.

Indications and Uses

Metformin is primarily indicated for the management of type 2 diabetes mellitus. It may be prescribed as monotherapy or in combination with other antidiabetic medications like sulfonylureas or insulin.

Mechanism of Action

Metformin primarily works by inhibiting hepatic gluconeogenesis, which decreases glucose production by the liver. It also improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike other antidiabetic agents, it does not induce hypoglycemia.

Dosage Forms

Metformin is available in several dosage forms including immediate-release tablets, extended-release tablets, and oral solutions. The immediate-release form is commonly available in 500 mg, 850 mg, and 1000 mg tablets, while extended-release forms are available in 500 mg and 750 mg tablets.

Administration Guidelines

Metformin should be taken with meals to minimize gastrointestinal side effects. Immediate-release formulations are typically taken two to three times a day, while extended-release formulations are taken once daily with the evening meal.

Starting Dose

The initial starting dose for immediate-release metformin is usually 500 mg taken twice a day or 850 mg once a day. Extended-release formulations often start at 500 mg once daily with the evening meal. The dose may be gradually increased to minimize gastrointestinal discomfort.

Maximum Dosage

The maximum recommended dose of metformin immediate release is 2550 mg per day, generally divided into three doses. For the extended-release form, the maximum dose is typically 2000 mg per day, with some extended-release formulations going up to 2500 mg per day.

Absorption and Distribution

Metformin is absorbed gradually following oral administration, with peak plasma concentrations reached approximately 2.5 hours after taking the immediate-release form. The extended-release formulation has a slower absorption, reaching peak plasma levels in around 7 hours.

Metabolism

Metformin is not metabolized by the liver. Instead, it is excreted unchanged in the urine. The lack of hepatic metabolism reduces the risk of liver-associated side effects but increases the importance of renal function monitoring.

Excretion

Approximately 90% of an ingested dose of metformin is excreted unchanged by the kidneys within 24 hours. The elimination half-life of metformin from plasma is approximately 6.5 hours in patients with normal renal function.

Contraindications

Metformin is contraindicated in patients with renal impairment, acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma, and hypersensitivity to metformin or any of its components.

Drug Interactions

Concurrent use of metformin with iodinated contrast media may increase the risk of lactic acidosis. Certain medications like cimetidine can increase metformin levels, while others like corticosteroids and diuretics may reduce its efficacy by raising blood glucose levels.

Adverse Effects

Common adverse effects of metformin include gastrointestinal symptoms such as diarrhea, nausea, and abdominal discomfort. Long-term use may be associated with vitamin B12 deficiency. Serious but rare side effects include lactic acidosis, characterized by high lactic acid levels in the blood which can be life-threatening.

Monitoring Parameters

Patients taking metformin require regular monitoring of renal function through serum creatinine levels or estimated glomerular filtration rate (eGFR). Assessing liver function tests and vitamin B12 levels periodically is also recommended.

Pregnancy and Breastfeeding

Metformin is classified as a pregnancy category B drug. While some studies suggest it may be safe for use during pregnancy, it should only be used when clearly needed. Metformin can pass into breast milk, so caution is advised when used while breastfeeding.

Patient Counseling

Patients should be informed about the importance of adhering to prescribed dietary and lifestyle modifications in conjunction with metformin therapy. They should also be educated on recognizing symptoms of gastrointestinal distress and signs of lactic acidosis, and advised to report any such symptoms immediately.

Storage Instructions

Metformin should be stored at room temperature, away from excessive moisture and heat. The medication must be kept out of the reach of children to prevent accidental ingestion.