• Metformin indications
• Uses of Metformin in details
• Metformin description
• Metformin dosage
• Metformin interactions
• Metformin side effects
• Metformin contraindications

What is Metformin?

Metformin is used to treat high blood sugar levels that are caused by a type of diabetes mellitus or sugar diabetes called type 2 diabetes. With this type of diabetes, insulin produced by the pancreas is not able to get sugar into the cells of the body where it can work properly. Using Metformin alone, with a type of oral antidiabetic medicine called a sulfonylurea, or with insulin, will help to lower blood sugar when it is too high and help restore the way you use food to make energy.

Many people can control type 2 diabetes with diet and exercise. Following a specially planned diet and exercise will always be important when you have diabetes, even when you are taking medicines. To work properly, the amount of Metformin you take must be balanced against the amount and type of food you eat and the amount of exercise you do. If you change your diet or exercise, you will want to test your blood sugar to find out if it is too low. Your doctor will teach you what to do if this happens.

Metformin does not help patients does not help patients who have insulin-dependent or type 1 diabetes because they cannot produce insulin from their pancreas gland. Their blood glucose is best controlled by insulin injections.

Metformin is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, Metformin is used in certain patients with the following medical conditions:

• Polycystic ovary syndrome.

Metformin indications

In maturity onset (non-insulin-dependent) obese diabetics and juvenile diabetics in whom diet alone has failed as monotherapy or in combination with insulin, glitazones or sulfonylureas. Also as an adjunct to diet and exercise to improve glycemic control in patients with type-2 diabetes.

Glitazones are used in combination with Metformin when glycemic control is poor on Metformin monotherapy and maximum tolerated dose (preferable) of Metformin has been tried. The combination of glitazone plus Metformin is preferred to glitazone plus sufonylurea, particularly for obese patients.

How should I use Metformin?

Use Metformin extended-release tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Metformin extended-release tablets. Talk to your pharmacist if you have questions about this information.
• Take Metformin extended-release tablets by mouth with the evening meal unless your doctor tells you otherwise.
• Swallow Metformin extended-release tablets whole. Do not break, crush, or chew before swallowing.
• Take Metformin extended-release tablets on a regular schedule to get the most benefit from it. Taking Metformin extended-release tablets at the same time each day will help you remember to take it.
• Continue to take Metformin extended-release tablets even if you feel well. Do not miss any doses.
• If you miss a dose of Metformin extended-release tablets, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Metformin extended-release tablets.

Uses of Metformin in details

Use: Labeled Indications

Diabetes mellitus, type 2: Management of type 2 diabetes mellitus when hyperglycemia cannot be managed with diet and exercise alone.

Note: If not contraindicated and if tolerated, Metformin is the preferred initial pharmacologic agent for type 2 diabetes management (ADA 2020).

Off Label Uses

Antipsychotic-induced weight gain

Data from multiple meta-analyses of randomized controlled trials with varying degrees of heterogeneity (primarily in patients with schizophrenia and schizoaffective disorder) support the use of Metformin in promoting modest weight loss and preventing weight gain associated with second-generation antipsychotics in adult patients

Metformin description

Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin may induce weight loss and is the drug of choice for obese NIDDM patients. Use of Metformin is associated with modest weight loss. When used alone, Metformin does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus Metformin was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and Metformin is appropriate.

Metformin dosage

Metformin Dosage

Generic name: Metformin 500mg

Dosage form: tablet, film coated, extended

The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with Metformin® or any other pharmacologic agent. Dosage of Metformin® must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose. The maximum recommended daily dose of Metformin® Extended-Release Tablets in adults is 2500 mg.

Metformin® should be taken with a full glass of water once daily with the evening meal. Metformin® should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

During treatment initiation and dose titration, fasting plasma glucose should be used to determine the therapeutic response to Metformin® and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of Metformin®, either when used as monotherapy or in combination with sulfonylurea or insulin.

Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness.

Short-term administration of Metformin® may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

Recommended Dosing Schedule

The usual starting dose of Metformin® (Metformin) Extended-Release Tablets is 1000 mg taken with a full glass of water once daily with the evening meal, although 500 mg may be utilized when clinically appropriate. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2500 mg once daily with the evening meal.

In randomized trials, patients currently treated with immediate-release Metformin were switched to Metformin®. Results of this trial suggest that patients receiving immediate-release Metformin treatment may be safely switched to Metformin® once daily at the same total daily dose, up to 2500 mg once daily. Following a switch from immediate-release Metformin to Metformin®, glycemic control should be closely monitored and dosage adjustments made accordingly.

Pediatrics– There is no pediatric information available for Metformin®.

Transfer From Other Antidiabetic Therapy

When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to Metformin®, no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first two weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

Concomitant Metformin® and

Oral Sulfonylurea Therapy in Adult Patients

If patients have not responded to four weeks of the maximum dose of Metformin® monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing Metformin® at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for Metformin plus glyburide (also known as glibenclamide). With concomitant Metformin® and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant Metformin® and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken.

If patients have not satisfactorily responded to one to three months of concomitant therapy with the maximum dose of Metformin® and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without Metformin®.

Concomitant Metformin® and Insulin Therapy in Adult Patients

The current insulin dose should be continued upon initiation of Metformin® therapy. Metformin® therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of Metformin® should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose for Metformin® Extended-Release Tablets is 2500 mg. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and Metformin®. Further adjustment should be individualized based on glucose-lowering response.

Specific Patient Populations

Metformin® is not recommended for use in pregnancy, and is not recommended in patients below the age of 17 years.

The initial and maintenance dosing of Metformin® should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of Metformin®.

Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly.

More about Metformin (Metformin)

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Consumer resources

• Fortomet extended-release tablets
• Metformin
• Metformin (Advanced Reading)

• Other brands: Glucophage, Glumetza, Glucophage XR, Riomet

Professional resources

• Metformin (FDA)
• Metformin (AHFS Monograph)

Related treatment guides

• Diabetes, Type 2
• Insulin Resistance Syndrome

Metformin interactions

See also:
What other drugs will affect Metformin?

Drug Interactions (Clinical Evaluation Of Drug Interactions Conducted With Immediate-Release Metformin)

Glyburide

In a single-dose interaction study in type 2 diabetes patients, co-administration of Metformin and glyburide did not result in any changes in either Metformin pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and Cmax were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain.

Furosemide

A single-dose, Metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by co-administration. Furosemide increased the Metformin plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in Metformin renal clearance. When administered with Metformin, the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of Metformin and furosemide when co-administered chronically.

Nifedipine

A single-dose, Metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that co-administration of nifedipine increased plasma Metformin Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Tmax and half-life were unaffected. Nifedipine appears to enhance the absorption of Metformin. Metformin had minimal effects on nifedipine.

Cationic Drugs

Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with Metformin by competing for common renal tubular transport systems. Such interaction between Metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, Metformin-cimetidine drug interaction studies, with a 60% increase in peak Metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood Metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of Metformin® and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.

Other

Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Metformin®, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving Metformin®, the patient should be observed closely for hypoglycemia.

In healthy volunteers, the pharmacokinetics of Metformin and propranolol, and Metformin and ibuprofen were not affected when coadministered in single-dose interaction studies.

Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.

Metformin side effects

See also:
What are the possible side effects of Metformin?

During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite which resolve spontaneously in most cases.

In a US double-blind clinical study of Metformin in patients with type 2 diabetes, a total of 141 patients received Metformin therapy (up to 2550 mg/day) and 145 patients received placebo. Adverse reactions reported in >5% of the Metformin patients, and that was more common in Metformin than placebo-treated patients, are listed in Table 2.

Diarrhea led to discontinuation of study medication in 6% of patients treated with Metformin. Additionally, the following adverse reactions were reported in >1% to <5% of Metformin patients and were more commonly reported with Metformin than placebo: Abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, increased sweating, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation.

In worldwide clinical trials, over 900 patients with type 2 diabetes have been treated with Metformin extended-release tablet in placebo- and active-controlled studies. In placebo-controlled trials, 781 patients were administered Metformin extended-release tablet and 195 patients received placebo. Adverse reactions reported in >5% of the Metformin extended-release tablet patients and that were more common in Metformin extended-release tablet than placebo treated patients, are listed in Table 3.

Diarrhea led to discontinuation of study medication in 0.6% of patients treated with Metformin extended-release tablet. Additionally, the following adverse reactions were reported in >1% to <5% of Metformin extended-release tablet patients and were more commonly reported with Metformin extended-release tablet than placebo: Abdominal pain, constipation, abdomen distention, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance.

In clinical trials with Metformin in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.

Other reported adverse events with use of Metformin are: Skin reactions eg, erythema, pruritus and urticaria; isolated reports of liver function tests abnormalities or hepatitis resolving upon Metformin discontinuation; lactic acidosis; decrease of vitamin B12 absorption with decrease of serum levels during long-term use of Metformin, consideration of such etiology is recommended if a patient presents with megaloplastic anaemia.

Metformin contraindications

See also:
What is the most important information I should know about Metformin?

Metformin® is contraindicated in patients with:

1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia.
2. Known hypersensitivity to Metformin.
3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

Metformin® should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.

WARNINGS

Lactic Acidosis:

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to Metformin accumulation during treatment with Metformin® (Metformin) Extended-Release Tablets; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/ L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When Metformin is implicated as the cause of lactic acidosis, Metformin plasma levels >5 μg/mL are generally found.

The reported incidence of lactic acidosis in patients receiving Metformin is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/ surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking Metformin® (Metformin) Extended-Release Tablets and by use of the minimum effective dose of Metformin®. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin® treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, Metformin® should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, Metformin® should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking Metformin®, since alcohol potentiates the effects of Metformin on lactate metabolism. In addition, Metformin® should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure.

The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur. Metformin® should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood Metformin levels may be useful. Once a patient is stabilized on any dose level of Metformin®, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.

Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking Metformin® do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling.

Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).

Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking Metformin®, the drug should be discontinued immediately and general supportive measures promptly instituted. Because Metformin is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated Metformin. Such management often results in prompt reversal of symptoms and recovery.

Active ingredient matches for Metformin:

Metformin

References

1. PubChem. "metformin". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
2. DrugBank. "metformin". http://www.drugbank.ca/drugs/DB00331 (accessed September 17, 2018).
3. MeSH. "Hypoglycemic Agents". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).

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Information checked by Dr. Sachin Kumar, MD Pharmacology