Metformin


Generic Medicine Info
Indications and Dosage
Oral
Type 2 diabetes mellitus
Adult: As an adjunct to diet and exercise: Treatment: Monotherapy or in combination with other antidiabetic agents, or with insulin: As conventional tab or solution: Initially, 500-850 mg 1-3 times daily, gradually increase at intervals of at least 1 week, or alternatively, 10-15 days according to patient’s response. Max: 2,550-3,000 mg daily in 3 divided doses. As extended-release tab: Initially, 500-1,000 mg once daily, increase at intervals of at least 1 week, or alternatively, 10-15 days. Max: 1,500-2,000 mg daily. Prophylaxis: To reduce the risk or delay the onset of type 2 diabetes mellitus in high-risk individuals (e.g. overweight adults or those with impaired glucose tolerance/fasting glucose): As extended-release tab: Initially, 500 mg once daily, gradually increase at intervals of 10-15 days, according to patient’s response. Max: 1,500-2,000 mg daily. Dosage recommendations vary among countries or individual products. Refer to country- or product-specific guidelines.
Child: ≥10 years As monotherapy or in combination with insulin: As conventional tab or solution: Initially, 500 mg once daily or bid, or 850 mg once daily, gradually increase at intervals of at least 1 week, or alternatively, 10-15 days according to patient’s response. Max: 2,000 mg daily in 2 or 3 divided doses. Dosage recommendations may vary among countries or individual products. Refer to country- or product-specific guidelines.
Renal Impairment
eGFR <30 mL/min: Contraindicated. eGFR 30-44 mL/min: Max: 1,000 mg daily. eGFR 45-59 mL/min: Max: 2,000 mg daily. eGFR 60-89 mL/min: Max: As conventional tab or solution: 3,000 mg daily. As extended-release tab: 2,000 mg daily. All doses to be taken in 2-3 divided doses.
Hepatic Impairment
Contraindicated.
Administration
Should be taken with food. XR tab: Swallow whole, do not split/crush/chew.
Contraindications
Acute or chronic metabolic acidosis, including diabetic ketoacidosis (with or without coma); diabetic pre-coma; acute conditions which may alter renal function (e.g. dehydration, severe infection, shock), acute or chronic conditions which may cause tissue hypoxia (e.g. acute unstable heart failure; respiratory failure, recent MI; pulmonary embolism, acute significant blood loss, sepsis, gangrene, pancreatitis), acute alcohol intoxication or alcoholism. Hepatic or severe renal impairment (eGFR <30 mL/min). Concomitant intravascular administration of iodinated contrast agents.
Special Precautions
Patients with risk factors for lactic acidosis, stable chronic heart failure, prerenal azotaemia. Mild to moderate renal impairment. Children and elderly. Pregnancy and lactation. Not indicated for use in patients with type 1 diabetes mellitus or diabetic ketoacidosis. Patients undergoing surgical procedures.
Adverse Reactions
Significant: Vitamin B12 deficiency (prolonged use).
Gastrointestinal disorders: Nausea, vomiting, abdominal pain or distress, flatulence, diarrhoea, dyspepsia, taste disturbance.
Metabolism and nutrition disorders: Loss of appetite.
Musculoskeletal and connective tissue disorders: Asthenia.
Potentially Fatal: Lactic acidosis.
PO: Z (Studies found no association with congenital malformation or neonatal harm, but long-term effects on children are unknown. Consult local guidelines for use in gestational diabetes and PCOS.)
Monitoring Parameters
Monitor urine for glucose and ketones, fasting blood sugar, HbA1c (at least twice yearly in patients with stable glycaemic control; quarterly in patients not meeting therapy goals or with changes in treatment); renal function prior to initiation of therapy and then annually or more frequently in the elderly and patients at risk for renal impairment; liver function at baseline; haematologic parameters at baseline and annually thereafter; vitamin B12 serum concentration every 2-3 years (prolonged use). Monitor for signs and symptoms of lactic acidosis and vitamin B12 deficiency.
Overdosage
Symptoms: Lactic acidosis manifested as malaise, myalgia, respiratory distress, increasing somnolence and abdominal distress. Hypothermia, hypotension and resistant bradyarrhythmias may be associated with more marked acidosis. Management: Perform haemodialysis to remove lactate and metformin in the blood.
Drug Interactions
Increased risk of lactic acidosis with carbonic anhydrase inhibitors (e.g. acetazolamide, dichlorphenamide, topiramate, zonisamide), NSAIDs, including cyclo-oxygenase (COX) II inhibitors; ACE inhibitors, angiotensin II receptor antagonists, and loop diuretics. Increased risk of hypoglycaemia with other antidiabetic agents (e.g. sulfonylurea, meglitinides, insulin). Increased plasma concentration with organic cation transporters (OCT)2 inhibitors (e.g. cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole). Reduced efficacy with OCT1 inhibitors (e.g. verapamil). Increased gastrointestinal absorption and efficacy with OCT1 inducers (e.g. rifampicin). Altered efficacy and renal elimination with OCT1 and OCT2 inhibitors (e.g. crizotinib, olaparib). May produce hyperglycaemia with corticosteroids, thiazide diuretics, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, Ca channel blockers, and isoniazid. May diminish the therapeutic effect of anticoagulants (e.g. warfarin).
Potentially Fatal: Contrast-induced nephropathy and increased risk of lactic acidosis with concomitant use of intravascular iodinated contrast agents.
Food Interaction
Food slightly delays and decreases the extent of absorption of metformin. Increased risk of lactic acidosis with alcohol.
Action
Description: Metformin is a biguanide antihyperglycaemic agent which improves glucose tolerance by lowering both basal and postprandial plasma glucose. It exerts its effect by decreasing hepatic glucose production through inhibition of gluconeogenesis and glycogenolysis, delaying intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilisation.
Onset: Within days.
Pharmacokinetics:
Absorption: Slowly and incompletely absorbed from the gastrointestinal tract. Food slightly delays and decreases the extent of absorption. Absolute bioavailability: 50-60%. Time to peak plasma concentration: 2-3 hours (immediate-release); 7 hours, range: 4-8 hours (extended-release).
Distribution: Concentrates in liver, kidney, gastrointestinal tract and salivary gland tissue. Crosses the placenta and enters breast milk (small amounts). Volume of distribution: 654 ± 358 L.
Metabolism: Not metabolised.
Excretion: Via urine (approx 90%, as unchanged drug). Elimination half-life: 4-9 hours (plasma); approx 17.6 hours (blood).
Chemical Structure

Chemical Structure Image
Metformin

Source: National Center for Biotechnology Information. PubChem Database. Metformin, CID=4091, https://pubchem.ncbi.nlm.nih.gov/compound/Metformin (accessed on Jan. 20, 2020)

Storage
Store below 30°C. Protect from heat, light and moisture.
MIMS Class
Antidiabetic Agents
ATC Classification
A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.
References
Anon. Metformin. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 04/02/2022.

Anon. Metformin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/02/2022.

Buckingham R (ed). Metformin Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/02/2022.

Fortamet Extended-Release Tablet (Actavis Laboratories FL, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/02/2022.

Glucophage 500 mg Film-Coated Tablets (Merck Santé s.a.s.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 16/03/2022.

Glucophage XR 1000 mg Extended Release Tablet (Merck Santé s.a.s.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 16/03/2022.

Glucophage XR 500 mg Extended Release Tablet (Merck Santé s.a.s.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 16/03/2022.

Glucophage XR 750 mg Extended Release Tablet (Merck Santé s.a.s.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 16/03/2022.

Joint Formulary Committee. Metformin Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/02/2022.

Metformin 500 mg Film-Coated Tablets (Teva UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 04/02/2022.

Metformin Colonis 1,000 mg/5 mL Oral Solution (Colonis Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 04/02/2022.

Metformin Hydrochloride 500 mg Prolonged-Release Tablets (Generic Partners UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 04/02/2022.

Metformin Hydrochloride Amarox 750 mg Prolonged-Release Tablets (Amarox Limited). MHRA. https://products.mhra.gov.uk. Accessed 04/02/2022.

Metformin Hydrochloride Oral Solution (Trupharma, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 16/03/2022.

Metformin Hydrochloride Tablet, Film Coated (Laurus Labs Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 16/03/2022.

Mylan New Zealand Ltd. Metformin Mylan, 500 mg, 850 mg & 1000 mg Film-Coated Tablet data sheet 25 February 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 04/02/2022.

Disclaimer: This information is independently developed by MIMS based on Metformin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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