Treatment of type 2 diabetes mellitus, particularly in overweight patients when dietary management and exercise alone does not result in adequate glycaemic control. In adults: Metformin may be used as monotherapy or in combination with other oral antidiabetic agents or with insulin. In children from 10 years of age and adolescents: Metformin may be used as monotherapy or in combination with insulin. A reduction of diabetic complications has been shown in overweight type 2 diabetic adult patients treated with metformin as first-line therapy after diet failure.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals. Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses. Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew. Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose. Children: Metformin extended release tablet has not been studied in children. Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m2. Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m2.

Hypersensitivity to the active substance or to any of the excipients. Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis). Severe renal failure (GFR <30 mL/min). Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock. Acute or chronic disease, which may cause tissue hypoxia such as: cardiac or respiratory failure, recent myocardial infarction, shock, Hepatic insufciency, acute alcohol intoxication, alcoholism.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Blood and lymphatic system disorders: Not known: Hemolytic anemia Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known) Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability. Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation. Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus. Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.