| Recommended Dose and Dosage Regimen | The recommended starting dose of metformin for adults with type 2 diabetes mellitus is 500 mg or 850 mg orally once daily with meals or immediately after meals, with gradual titration based on glycemic control and tolerability. The maximum recommended dose of metformin immediate-release tablets is 2550 mg daily in divided doses. Extended-release formulations of metformin (e.g., Glucophage XR) may be initiated at 500 mg orally once daily with the evening meal, with gradual titration up to a maximum dose of 2000 mg daily. Dosage adjustments are necessary in patients with renal impairment, as metformin is contraindicated in severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m²) and should be used with caution in mild to moderate renal impairment (eGFR 30-60 mL/min/1.73 m²). Follow your healthcare provider’s instructions regarding dosing and administration. |
| Frequency of Administration | Metformin is typically administered orally once or twice daily with meals to minimize gastrointestinal side effects and improve tolerability. |
| Route of Administration | Metformin is available as oral tablets or extended-release tablets for ingestion. |
| Mechanism of Action (MOA) | Metformin is a biguanide antihyperglycemic agent that improves glycemic control in patients with type 2 diabetes mellitus. It exerts its pharmacological effects primarily by decreasing hepatic glucose production, reducing intestinal glucose absorption, and enhancing peripheral glucose uptake and utilization. Metformin activates adenosine monophosphate-activated protein kinase (AMPK) in hepatocytes, leading to inhibition of gluconeogenesis and activation of glucose uptake in skeletal muscle and adipose tissue. Additionally, metformin may have beneficial effects on insulin sensitivity, lipid metabolism, and cardiovascular risk factors. |
| Pharmacokinetics (PK) | Metformin is well absorbed after oral administration, with peak plasma concentrations reached within 2-4 hours. It is not extensively bound to plasma proteins and exhibits minimal metabolism, primarily undergoing renal elimination via tubular secretion without undergoing hepatic metabolism. The elimination half-life of metformin is approximately 4-8 hours, allowing for once- or twice-daily dosing. Metformin is excreted unchanged in the urine, and dosage adjustments are necessary in patients with renal impairment to minimize the risk of lactic acidosis. |
| Pharmacodynamics (PD) | Metformin exerts its pharmacodynamic effects by reducing hyperglycemia through multiple mechanisms. It decreases hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, primarily through activation of AMPK in the liver. Metformin also improves peripheral insulin sensitivity and glucose uptake in skeletal muscle and adipose tissue, leading to enhanced glucose utilization and decreased insulin resistance. Additionally, metformin may reduce intestinal glucose absorption and lower fasting and postprandial blood glucose levels without increasing insulin secretion or causing hypoglycemia in the absence of concomitant sulfonylurea or insulin therapy. |
| Pathophysiology | Metformin is indicated for the management of type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in adults. Type 2 diabetes mellitus is characterized by insulin resistance and relative insulin deficiency, leading to hyperglycemia and associated complications such as cardiovascular disease, neuropathy, nephropathy, and retinopathy. Metformin helps regulate blood glucose levels by decreasing hepatic glucose production, enhancing peripheral glucose uptake, and improving insulin sensitivity, thereby reducing fasting and postprandial hyperglycemia. |
| Primary Indications | Type 2 diabetes mellitus. |
| Contraindications | Contraindications to metformin use include hypersensitivity to metformin or any component of the formulation, severe renal impairment (eGFR <30 mL/min/1.73 m²), acute or chronic metabolic acidosis, including diabetic ketoacidosis, and severe hypoxemia. Metformin should be temporarily discontinued before iodinated contrast imaging procedures in patients with an eGFR <60 mL/min/1.73 m² and restarted 48 hours after the procedure if renal function is stable. Use caution in patients with hepatic impairment, heart failure, or conditions predisposing to lactic acidosis. |
| Purpose of Taking Medication | The purpose of metformin therapy is to improve glycemic control in patients with type 2 diabetes mellitus by decreasing hepatic glucose production, enhancing peripheral glucose uptake, and improving insulin sensitivity. Metformin is used as first-line therapy for the management of type 2 diabetes mellitus and may be prescribed alone or in combination with other antidiabetic medications, such as sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, or insulin, to achieve target blood glucose levels and reduce the risk of diabetes-related complications. |
| Usage Instructions | Take metformin orally with meals or immediately after meals to minimize gastrointestinal side effects, as directed by your healthcare provider. Swallow the tablets whole with a full glass of water; do not crush, chew, or split the tablets unless instructed otherwise. Follow your healthcare provider’s instructions regarding dosing schedule, titration, and adjustments. |
| Precautions and Care | Patients taking metformin should be advised to adhere to a healthy lifestyle, including regular physical activity, a balanced diet, and weight management, to optimize glycemic control and reduce cardiovascular risk factors. Monitor for signs and symptoms of lactic acidosis, including hyperventilation, myalgia, malaise, and abdominal discomfort, especially in patients with renal impairment or other predisposing factors. Educate patients about the risk of vitamin B12 deficiency and consider periodic monitoring of vitamin B12 levels in long-term metformin users. |
| Dietary Considerations | There are no specific dietary restrictions associated with metformin use. Maintain a balanced diet and adequate hydration to support overall health and well-being during diabetes management. Avoid excessive alcohol consumption, as it may increase the risk of lactic acidosis and impair glycemic control. |
| Missed Dose | If a dose of metformin is missed, take it as soon as remembered, unless it is almost time for the next scheduled dose. Do not double the dose to make up for a missed one. Resume the regular dosing schedule and consult your healthcare provider if unsure about missed doses or medication instructions. |
| Possible Side Effects | Common side effects of metformin may include gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal discomfort, and loss of appetite, particularly during initiation of therapy or dose escalation. These side effects are usually transient and can often be minimized by taking metformin with meals or using extended-release formulations. Rarely, metformin may cause lactic acidosis, a serious and potentially life-threatening complication. Contact your healthcare provider immediately if you experience symptoms of lactic acidosis, such as weakness, fatigue, difficulty breathing, or irregular heartbeat. |
| Storage and Disposal | Store metformin tablets at room temperature away from moisture and heat. Keep the medication out of reach of children and pets. Unused or expired medication should be disposed of properly according to local regulations or guidelines for pharmaceutical waste disposal. |
| Overdose or Emergency | In case of metformin overdose or emergency, seek immediate medical attention or contact a poison control center. Overdose may lead to lactic acidosis, which requires prompt medical intervention, including supportive measures and corrective treatment of metabolic acidosis. Hemodialysis may be necessary to remove metformin from the bloodstream in severe cases of overdose or renal impairment. |
| Monitoring and Laboratory Tests | Patients receiving metformin therapy require regular monitoring of glycemic control with periodic measurements of fasting blood glucose and hemoglobin A1c (HbA1c) levels. Renal function should be assessed before initiating metformin and periodically thereafter, particularly in patients at increased risk of renal impairment or lactic acidosis. Monitor for signs of vitamin B12 deficiency and consider periodic measurement of serum vitamin B12 levels, especially in long-term metformin users. |
