Metformin (Glucophage) – Uses, dosage, side effects

What is metformin (Glucophage)?

Metformin is an oral medication that helps control blood sugar levels and that is mainly used for the treatment of type 2 diabetes. It works by decreasing insulin resistance (increasing insulin sensitivity), decreasing the amount of glucose released into the blood stream by the liver, and also by decreasing intestinal absorption of glucose. Unlike other medications, metformin does not increase the amount of insulin produced by the body and for this reason the risk of hypoglycemia (low blood sugar) is very low when taken alone. Metformin lowers both fasting glucose levels and postprandial glucose levels.

Common brand names for metformin include Glucophage and Fortamet.

metformin glucophage 500mg tablets generic medication
By User:Ash – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=38698964

Metformin dosage

Like any other medication, metformin dosage varies based on each individual’s characteristics and on the specific indication. Always follow the advice of your prescribing doctor which will tell you when to take the medication and how much of it you need.

As a general rule, physicians will start with a low dose and adjust over time based on your body’s response. Sometimes, a combination therapy is needed, meaning you will be prescribed also another medication to manage high blood sugar such as insulin or other tablets to take by mouth with a different mechanism of action.

Metformin is available as 500-750-850-1000 mg tablets. Typical dose varies between 500 to 2550 mg per day and it is taken with a meal to reduce the gastrointestinal side effects. The usual starting dose for an adult is 500 mg once or twice a day with a meal, which can then be increased over the course of a few weeks up to 2-3 grams daily (depending on national guidelines and the coexistence of other medical conditions) to be split over the three main meals.

Metformin is also available as liquid formulation.

Extended Release (XR) vs Instant Release (IR)

Metformin exists in two different formulation. The regular or instant release formulation and an extended release formulation. While the former is taken up to 3 times per day, the latter is generally taken only once, with the evening meal. Extended release tablets should not be crushed, chewed or split into smaller pieces.

Metformin uses

Metformin is mainly used for the treatment of type 2 diabetes also known as diabetes mellitus.

It is generally not indicated in type 1 diabetes, although in the last years endocrinologists are beginning to prescribe metformin also to selected patients with type 1 diabetes in conjunction with injectable insulin.

Other uses for metformin include:

Metformin in pregnancy

Metformin use in pregnancy is increasing worldwide after randomized control trials and large case-control studies are proving its safety and efficacy. Indications in pregnancy include the treatment of type 2 diabetes with or without insulin, the treatment of gestational diabetes as an alternative to or in conjunction with insulin, the management of PCOS during pregnancy and the use of metformin to increase fertility in women with PCOS; it is also being used in pregnant nondiabetic women with obesity.

From studies, there is no evidence of increased risk of miscarriage or malformation when metformin is started before or during pregnancy.

Metformin while breastfeeding

Although studies show trace amount of metformin are excreted in breast milk, such amounts are highly unlikely to have any effect on breastfed babies. Metformin seems to have no adverse effects on growth and overall development and is safe for use during lactation.

Metformin in PCOS and for fertility

Women with PCOS have increased insulin resistance which leads to increased insulin production; hyperinsulinemia causes an increase in androgen hormones production by the ovaries which plays a central role in PCOS. By lowering insulin resistance, metformin is an effective treatment for PCOS and is able to increase fertility, reduce early pregnancy loss rates and preterm labor, and prevent fetal growth restrictions, while having no teratogenic effects.

Side effects

Like any other medication, metformin may cause side effects. The following are the most commonly reported:

  • Diarrhea
  • Nausea
  • Vomiting
  • Bloating

Tell your doctor about any symptoms you may experience after taking metformin.

Precautions and warnings

Metformin interacts with many medications. Tell your doctor and pharmacist about any other drug or supplement you are taking.

You may have to stop this medication before surgeries or before diagnostic imaging techniques which require the injection of contrast. Ask your doctor for instructions.

Allergic reactions to metformin are rare. However, if you experience a rash, itching, swelling, dizziness or trouble breathing seek immediate medical attention.

Metformin may increase the risk of lactic acidosis which is a serious and life-threatening condition. If you experience general malaise, muscle soreness, abdominal pain or trouble breathing seek immediate medical attention.

Ask your doctor or pharmacist for more information on precautions and warnings.

Does metformin cause cancer? Recall of Metformin Extended Release 2020

In May 2020, the FDA announced that they found levels of NDMA above the acceptable limit in several lots of extended release metformin. NDMA is a common molecule found in food and water. When ingested at low levels it is not expected to cause any harm, however when safety limits are exceeded for a long period of time it becomes a carcinogenic, meaning it increases the risk of cancer. Metformin itself is not a carcinogenic and you should keep taking it as prescribed by your physician. Only some lots have been found to be contaminated and the FDA has taken steps to correct this issue by making sure all lots are tested before introducing them to the US market. Ask your doctor for more information on this matter.


Sources
  • Metformin
    C Corcoran, TF Jacobs – StatPearls, Apr 2020
  • Metformin versus insulin for the treatment of gestational diabetes.
    JA Rowan, WM Hague, WZ Gao – New England Journal of Medicine, May 2008
  • Metformin exposure in first trimester of pregnancy and risk of all or specific congenital anomalies: exploratory case-control study.
    JE Given, M Loane, E Garne – The British Medical Journal, Jun 2018
  • Effects of metformin use in pregnant patients with polycystic ovary syndrome.
    P Kumar, K Khan – Journal of Human Reproductive Sciences, May 2012
  • Metformin in Pregnancy: Mechanisms and Clinical Applications.
    S Hyer, J Balani, H Shehata – International Journal of Molecular Sciences, Jul 2018
  • Use of hypoglycemic drugs during lactation.
    MM Glatstein, N Djokanovic – Canadian Family Physician Journal, Apr 2009
  • British National Formulary 2020
  • US Food and Drug Administration (FDA)
  • US National Library of Medicine – MedilinePlus

 

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