Ormin 500 mg is indicated for the treatment of type 2 diabetes mellitus, especially in overweight patients when diet control and exercise alone are not sufficient to achieve adequate glycaemic control.

• In adults: Ormin can be used as monotherapy or in combination with other oral antidiabetic drugs or insulin.
• In children from 10 years of age and adolescents: Ormin may be used as monotherapy or in combination with insulin.

A reduction in diabetic complications has been demonstrated in overweight type 2 diabetic adult patients treated with Ormin as first-line therapy after failure of dietary management.

Metformin is a biguanide class oral antihyperglycaemic agent used in the management of type 2 diabetes mellitus. It reduces both basal and postprandial blood glucose levels. Its mechanism of action differs from sulfonylureas and it does not cause hypoglycaemia when used alone. Metformin decreases hepatic glucose production, reduces intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral uptake and utilization of glucose.

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. Assess risk/benefit of continuing if eGFR falls below 45 mL/min/1.73 m².

• Hypersensitivity to Metformin or any of the excipients.
• Any form of acute metabolic acidosis (including lactic acidosis or diabetic ketoacidosis).
• Severe renal impairment (GFR < 30 mL/min).
• Acute conditions that may affect renal function such as dehydration, severe infection, or shock.
• Acute or chronic diseases causing tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction, shock, hepatic insufficiency, acute alcohol intoxication, or alcoholism.

Blood and lymphatic system disorders: Not known—hemolytic anemia.

Metabolism and nutrition disorders: Very rare—lactic acidosis. Long-term use may reduce vitamin B12 absorption leading to decreased serum levels. Consider vitamin B12 deficiency if megaloblastic anemia is present. Cases of peripheral neuropathy due to vitamin B12 deficiency have been reported post-marketing (frequency unknown).

Nervous system disorders: Common—taste disturbance. Not known—encephalopathy.

Gastrointestinal disorders: Very common—nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These effects usually occur at the start of treatment and resolve spontaneously. Taking metformin in 2–3 divided doses with or after meals and gradual dose escalation may improve tolerability.

Hepatobiliary disorders: Very rare—abnormal liver function tests or hepatitis, which resolve after discontinuation.

Skin and subcutaneous tissue disorders: Very rare—skin reactions such as erythema, pruritus, and urticaria.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or pre-existing) increases the risk of congenital abnormalities and perinatal mortality. When pregnancy is planned or during pregnancy, insulin is recommended instead of metformin to maintain near-normal blood glucose levels and reduce fetal risk.

Breastfeeding: Metformin is excreted in human breast milk. No adverse effects have been observed in breastfed infants; however, due to limited data, breastfeeding is not recommended during treatment. A decision should be made whether to discontinue breastfeeding or the drug, considering the benefit to the mother and potential risk to the infant.

Metformin is primarily excreted by the kidneys; therefore, impaired renal function increases the risk of drug accumulation and lactic acidosis. It may reduce vitamin B12 levels and increase the risk of hypoglycemia when used with insulin or insulin secretagogues.

Renal function should be monitored regularly in all diabetic patients. Metformin should be discontinued 2–3 days before surgical procedures and diagnostic studies such as intravenous urography or angiography, and restarted only after renal function is confirmed normal. It should be avoided in conditions associated with dehydration, severe infection, or trauma. Patients on long-term therapy should have annual vitamin B12 level monitoring due to reduced absorption risk. During combination therapy with sulfonylureas, blood glucose monitoring is essential due to risk of hypoglycemia. Hospital supervision is recommended when initiating metformin with insulin until appropriate dose balance is achieved. Reduced renal clearance has been reported with concomitant cimetidine use; therefore, dose adjustment may be required. Interaction with anticoagulants is also possible, and dosage adjustment may be necessary.

Elderly: Due to the increased possibility of reduced renal function in elderly patients, the dose of metformin should be adjusted according to renal function. Regular monitoring of renal function is required.

Pediatric population: The diagnosis of type 2 diabetes mellitus must be confirmed before starting metformin therapy. In controlled clinical studies of one-year duration, no adverse effect on growth and puberty was observed; however, no long-term data are available. Therefore, careful long-term monitoring of growth and pubertal development is recommended, especially in prepubescent children.

Children aged 10–12 years: Extra caution is advised when prescribing metformin to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidneys, creatinine clearance (estimated using the Cockcroft-Gault formula from serum creatinine) should be assessed before starting treatment and regularly thereafter:

• At least annually in patients with normal renal function
• At least 2–4 times per year in patients with borderline renal function and in elderly patients

Reduced renal function is common and often asymptomatic in elderly patients. Special caution is required in conditions that may impair renal function, such as initiation of antihypertensive drugs, diuretics, or NSAIDs. GFR should be assessed before starting therapy and regularly during treatment. Metformin is contraindicated in patients with GFR < 30 mL/min and should be temporarily discontinued in conditions that may affect renal function.

Hypoglycemia has not been reported with metformin doses up to 85 g, although lactic acidosis has occurred in such cases. Lactic acidosis is a medical emergency and requires hospital treatment. Hemodialysis is the most effective method for removal of lactate and metformin.

Biguanides

Store below 30°C, protect from light and moisture. Keep out of reach of children.