Metformin/ja: Difference between revisions

'''メトホルミン'''（'''Metformin'''）は、'''グルコファージ（'''Glucophage'''）などの商品名で販売されており、特に[[overweight/ja|太りすぎ]]の[[diabetes mellitus type 2/ja|2型糖尿病]]の治療のための主要な[[first-line treatment/ja|第一選択]]医薬品である。また、[[polycystic ovary syndrome/ja|多嚢胞性卵巣症候群]]の治療にも用いられる。[[antipsychotic/ja|抗精神病薬]]を服用している人の[[metabolic syndrome/ja|メタボリックシンドローム]]のリスクを軽減するために、適応外の補助薬として使用されることもある。

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=== Formulations ===

[[File:Metformin 500mg Tablets.jpg|thumb|right|Generic metformin 500-mg tablets, as sold in the United Kingdom]]

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The name "Metformin" is the [[British Approved Name|BAN]], [[United States Adopted Name|USAN]], and [[International Nonproprietary Name|INN]] for this medication, and is sold under several [[trade name]]s. Common brand names include Glucophage, Riomet, Fortamet, and Glumetza in the US. In other areas of the world, there is also Obimet, Gluformin, Dianben, Diabex, Diaformin, Metsol, Siofor, Metfogamma and Glifor. There are several formulations of Metformin available to the market, and all but the liquid form have generic equivalents. Metformin IR (immediate release) is available in 500-, 850-, and 1000-mg tablets, while Metformin XR (extended release) is available in 500-, 750-, and 1000-mg strengths (also sold as Fortamet, Glumetza, and Glucophage XR in the US). Also available is liquid metformin (sold as Riomet in the US), where 5&nbsp;mL of solution contains the same amount of drug as a 500-mg tablet.

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==== Combination with other medications ====

Several are available as [[fixed-dose combination]]s, with the potential to reduce pill burden, decrease cost, and simplify administration.

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===== Thiazolidinediones (glitazones) =====

======Rosiglitazone======

A combination of metformin and [[rosiglitazone]] was released in 2002, and sold as Avandamet by [[GlaxoSmithKline]], or as a generic medication. Formulations are 500/1, 500/2, 500/4, 1000/2, and 1000&nbsp;mg/4&nbsp;mg of metformin/rosiglitazone.

In 2005, the stock of Avandamet was removed from the market, after inspections showed the factory where it was produced was violating [[good manufacturing practice]]s. The medication pair continued to be prescribed separately, and Avandamet was again available by the end of that year. A generic formulation of metformin/rosiglitazone from [[Teva Pharmaceutical Industries|Teva]] received tentative approval from the FDA and reached the market in early 2012.

However, following a meta-analysis in 2007 that linked the medication's use to an increased risk of [[Myocardial infarction|heart attack]], concerns were raised over the safety of medicines containing rosiglitazone. In September 2010, the [[European Medicines Agency]] recommended that the medication be suspended from the European market because the benefits of rosiglitazone no longer outweighed the risks.

In November 2013, the FDA lifted its earlier restrictions on rosiglitazone after reviewing the results of the 2009 RECORD clinical trial (a six-year, open-label [[randomized control trial]]), which failed to show elevated risk of heart attack or death associated with the medication.

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====== Pioglitazone ======

The combination of [[Pioglitazone/metformin|metformin and pioglitazone]] (Actoplus Met, Piomet, Politor, Glubrava) is available in the US and the European Union.

===== DPP-4 inhibitors =====

[[Dipeptidyl peptidase-4 inhibitor]]s inhibit [[dipeptidyl peptidase-4]] and thus reduce [[glucagon]] and blood glucose levels.

DPP-4 inhibitors combined with metformin include a [[sitagliptin/metformin]] combination (Janumet), a [[saxagliptin/metformin]] combination (Kombiglyze XR, Komboglyze), and an [[alogliptin/metformin]] combination (Kazano, Vipdomet).

[[Linagliptin]] combined with metformin hydrochloride is sold under the brand name Jentadueto. As of August 2021, linagliptin/metformin is available as a [[generic medicine]] in the US.

=====SGLT-2 inhibitors=====

There are combinations of metformin with the [[SGLT-2 inhibitor]]s [[Dapagliflozin/metformin|dapagliflozin]], [[Empagliflozin/metformin|empagliflozin]], and [[Canagliflozin/metformin|canagliflozin]].

===== Sulfonylureas =====

[[Sulfonylurea]]s act by increasing insulin release from the [[beta cell]]s in the [[pancreas]].

Metformin is available combined with the sulfonylureas [[glipizide]] (Metaglip) and [[glibenclamide]] (US: glyburide) (Glucovance). Generic formulations of metformin/glipizide and metformin/glibenclamide are available (the latter is more popular).

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===== Meglitinide =====

[[Meglitinide]]s are similar to sulfonylureas, as they bind to beta cells in the pancreas, but differ by the site of binding to the intended receptor and the drugs' affinities to the receptor. As a result, they have a shorter duration of action compared to sulfonylureas, and require higher blood glucose levels to begin to secrete insulin. Both meglitinides, known as nateglinide and repanglinide, is sold in formulations combined with metformin. A [[repaglinide]]/metformin combination is sold as Prandimet, or as its generic equivalent.

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===== Triple combination =====

The combination of metformin with [[pioglitazone]] and glibenclamide is available in India as Accuglim-MP, Adglim MP, and Alnamet-GP, along with the Philippines as Tri-Senza.

The combination of metformin with pioglitazone and [[lipoic acid]] is available in Turkey as Pional.

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=== Impurities ===

{{See also|Ranitidine#impurities}}

In December 2019, the US FDA announced that it learned that some metformin medicines manufactured outside the United States might contain a nitrosamine impurity called [[N-nitrosodimethylamine]] (NDMA), classified as a probable human carcinogen, at low levels. Health Canada announced that it was assessing NDMA levels in metformin.

In February 2020, [[Health Canada]] announced a recall of Apotex immediate-release metformin, followed in March by recalls of Ranbaxy metformin and in March by Jamp metformin.

In May 2020, the FDA asked five companies to voluntarily recall their [[sustained-release]] metformin products. The five companies were not named, but they were revealed to be Amneal Pharmaceuticals, Actavis Pharma, Apotex Corp, Lupin Pharma, and Marksans Pharma Limited in a letter sent to [[Valisure]], the pharmacy that had first alerted the FDA to this contaminant in metformin via a Citizen Petition.

In July 2020, Lupin Pharmaceuticals pulled all [[Lot number|lots]] (batches) of metformin after discovering unacceptably high levels of NDMA in tested samples.

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== Research ==

* [[Non-alcoholic fatty liver disease]]

* [[Premature puberty]]

* [[anti-cancer|Cancer]]

* [[Cardiovascular disease]] in people with diabetes

* [[Ageing|Aging]]

While metformin may reduce body weight in persons with [[fragile X syndrome]], whether it improves neurological or psychiatric symptoms is uncertain. Metformin has been studied in vivo (''[[Caenorhabditis elegans|C. elegans]]'' and [[Acheta domesticus|crickets]]) for effects on aging. A 2017 review found that people with diabetes who were taking metformin had lower all-cause mortality. They also had reduced cancer and cardiovascular disease compared with those on other therapies.

There is also some research suggesting that although metformin prevents diabetes, it does not reduce the risk of cancer and cardiovascular disease and thus does not extend lifespan in non-diabetic individuals. Furthermore, some studies suggest that long-term chronic use of metformin by healthy individuals may develop [[vitamin B12 deficiency]].