Medication used to treat diabetes
Metformin Pronunciation , met-FOR -min Trade names Glucophage, others Other names N ,N -dimethylbiguanide[ 1] AHFS /Drugs.com Monograph MedlinePlus a696005 License data
Pregnancy category Routes of administration By mouth Drug class Antidiabetic agent ATC code Legal status
Bioavailability 50–60%[ 10] [ 11] Protein binding Minimal[ 10] Metabolism Not by liver[ 10] Elimination half-life 4–8.7 hours[ 10] Excretion Urine (90%)[ 10]
N ,N -Dimethylimidodicarbonimidic diamide
CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG ChEBI ChEMBL CompTox Dashboard (EPA ) ECHA InfoCard 100.010.472 Formula C 4 H 11 N 5 Molar mass 129.167 g·mol−1 3D model (JSmol ) Density 1.3±0.1[ 12] g/cm3
CN(C)C(=N)N=C(N)N
as HCl: Cl.CN(C)C(=N)NC(N)=N
InChI=1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)
Key:XZWYZXLIPXDOLR-UHFFFAOYSA-N
as HCl: InChI=1S/C4H11N5.ClH/c1-9(2)4(7)8-3(5)6;/h1-2H3,(H5,5,6,7,8);1H
Key:OETHQSJEHLVLGH-UHFFFAOYSA-N
Metformin , sold under the brand name Glucophage , among others, is the main first-line medication for the treatment of type 2 diabetes ,[ 13] [ 14] [ 15] [ 16] particularly in people who are overweight .[ 14] It is also used in the treatment of polycystic ovary syndrome .[ 15] It is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics .[ 17] Metformin is not associated with weight gain[ 18] and is taken by mouth.[ 15]
Metformin is generally well tolerated.[ 19] Common adverse effects include diarrhea , nausea , and abdominal pain.[ 15] It has a small risk of causing low blood sugar .[ 15] High blood lactic acid level (acidosis ) is a concern if the medication is used in overly large doses or prescribed in people with severe kidney problems .[ 20] [ 21] It also inhibits inflammation.[ 22] [ 23]
Metformin is a biguanide anti-hyperglycemic agent.[ 15] It works by decreasing glucose production in the liver , increasing the insulin sensitivity of body tissues,[ 15] and increasing GDF15 secretion, which reduces appetite and caloric intake.[ 24] [ 25] [ 26] [ 27]
Metformin was first described in scientific literature in 1922 by Emil Werner and James Bell.[ 28] French physician Jean Sterne began the study in humans in the 1950s.[ 28] It was introduced as a medication in France in 1957. [ 15] [ 29] Metformin is on the World Health Organization's List of Essential Medicines ,[ 30] and is the most widely used medication for diabetes taken by mouth.[ 28] It is available as a generic medication .[ 15] In 2021, it was the second most commonly prescribed medication in the United States, with more than 91 million prescriptions.[ 31] [ 32]
^ Sirtori CR, Franceschini G, Galli-Kienle M, Cighetti G, Galli G, Bondioli A, et al. (December 1978). "Disposition of metformin (N,N-dimethylbiguanide) in man". Clinical Pharmacology and Therapeutics . 24 (6): 683–93. doi :10.1002/cpt1978246683 . PMID 710026 . S2CID 24531910 .
^ "Metformin Use During Pregnancy" . Drugs.com . 10 September 2019. Archived from the original on 16 April 2020. Retrieved 4 February 2020 .
^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)" . nctr-crs.fda.gov . FDA . Retrieved 22 October 2023 .
^ "Metformin SANDOZ metformin hydrochloride 850mg tablet bottle (148270)" . Therapeutic Goods Administration (TGA) . 27 May 2022. Retrieved 29 April 2023 .
^ Cite error: The named reference pmid6847752
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^ "Metformin Hydrochloride" . Health Canada . Archived from the original on 6 March 2023. Retrieved 6 March 2023 .
^ "Glucophage 500 mg film coated tablets - Summary of Product Characteristics (SmPC)" . (emc) . 25 October 2022. Archived from the original on 20 June 2022. Retrieved 5 March 2023 .
^ Cite error: The named reference Glucophage PI
was invoked but never defined (see the help page ).
^ "Metformin and metformin-containing medicines" . European Medicines Agency (EMA) . 13 October 2016. Archived from the original on 18 November 2023. Retrieved 10 June 2024 .
^ a b c d e Dunn CJ, Peters DH (May 1995). "Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus". Drugs . 49 (5): 721–49. doi :10.2165/00003495-199549050-00007 . PMID 7601013 .
^ Hundal RS, Inzucchi SE (2003). "Metformin: new understandings, new uses". Drugs . 63 (18): 1879–94. doi :10.2165/00003495-200363180-00001 . PMID 12930161 .
^ "Metformin" . www.chemsrc.com . Archived from the original on 12 June 2017. Retrieved 10 May 2018 .
^ Draznin B, Aroda VR, Bakris G, Benson G, Brown FM, Freeman R, et al. (January 2022). "9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022" . Diabetes Care . 45 (Suppl 1): S125–S143. doi :10.2337/dc22-s009 . PMID 34964831 . S2CID 245538347 .
^ a b Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. (January 2020). "2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD" . European Heart Journal . 41 (2): 255–323. doi :10.1093/eurheartj/ehz486 . PMID 31497854 .
^ a b c d e f g h i "Metformin Hydrochloride" . The American Society of Health-System Pharmacists. Archived from the original on 24 December 2016. Retrieved 2 January 2017 .
^ Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, et al. (June 2016). "Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis". Annals of Internal Medicine . 164 (11): 740–751. doi :10.7326/M15-2650 . PMID 27088241 . S2CID 32016657 .
^ de Silva VA, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R (October 2016). "Metformin in prevention and treatment of antipsychotic-induced weight gain: a systematic review and meta-analysis" . BMC Psychiatry . 16 (1): 341. doi :10.1186/s12888-016-1049-5 . PMC 5048618 . PMID 27716110 .
^ "Type 2 diabetes and metformin. First choice for monotherapy: weak evidence of efficacy but well-known and acceptable adverse effects". Prescrire International . 23 (154): 269–272. November 2014. PMID 25954799 .
^ Cite error: The named reference pmid26680745
was invoked but never defined (see the help page ).
^ Blumenberg A, Benabbas R, Sinert R, Jeng A, Wiener SW (April 2020). "Do Patients Die with or from Metformin-Associated Lactic Acidosis (MALA)? Systematic Review and Meta-analysis of pH and Lactate as Predictors of Mortality in MALA" . Journal of Medical Toxicology . 16 (2): 222–229. doi :10.1007/s13181-019-00755-6 . PMC 7099117 . PMID 31907741 .
^ Lipska KJ, Bailey CJ, Inzucchi SE (June 2011). "Use of metformin in the setting of mild-to-moderate renal insufficiency" . Diabetes Care . 34 (6): 1431–7. doi :10.2337/dc10-2361 . PMC 3114336 . PMID 21617112 .
^ Lin H, Ao H, Guo G, Liu M (2023). "The Role and Mechanism of Metformin in Inflammatory Diseases" . Journal of Inflammation Research . 16 : 5545–5564. doi :10.2147/JIR.S436147 . PMC 10680465 . PMID 38026260 .
^ Saisho Y (March 2015). "Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect". Endocrine, Metabolic & Immune Disorders Drug Targets . 15 (3): 196–205. doi :10.2174/1871530315666150316124019 . PMID 25772174 .
^ Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross JA, et al. (February 2020). "GDF15 mediates the effects of metformin on body weight and energy balance" . Nature . 578 (7795): 444–448. doi :10.1038/s41586-019-1911-y . PMC 7234839 . PMID 31875646 .
^ Day EA, Ford RJ, Smith BK, Mohammadi-Shemirani P, Morrow MR, Gutgesell RM, et al. (December 2019). "Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss". Nature Metabolism . 1 (12): 1202–1208. doi :10.1038/s42255-019-0146-4 . PMID 32694673 . S2CID 213199603 .
^ Pappachan JM, Viswanath AK (January 2017). "Medical Management of Diabesity: Do We Have Realistic Targets?". Current Diabetes Reports . 17 (1): 4. doi :10.1007/s11892-017-0828-9 . PMID 28101792 . S2CID 10289148 .
^ LaMoia TE, Butrico GM, Kalpage HA, Goedeke L, Hubbard BT, Vatner DF, et al. (March 2022). "Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis" . Proceedings of the National Academy of Sciences of the United States of America . 119 (10): e2122287119. Bibcode :2022PNAS..11922287L . doi :10.1073/pnas.2122287119 . PMC 8916010 . PMID 35238637 .
^ a b c Fischer J (2010). Analogue-based Drug Discovery II . John Wiley & Sons. p. 49. ISBN 978-3-527-63212-1 . Archived from the original on 8 September 2017.
^ Stargrove MB, Treasure J, McKee DL (2008). Herb, nutrient, and drug interactions : clinical implications and therapeutic strategies . St. Louis, Mo.: Mosby/Elsevier. p. 217. ISBN 978-0-323-02964-3 . Archived from the original on 8 September 2017.
^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019 . Geneva: World Health Organization. hdl :10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^ "The Top 300 of 2021" . ClinCalc . Archived from the original on 15 January 2024. Retrieved 14 January 2024 .
^ "Metformin - Drug Usage Statistics" . ClinCalc . Archived from the original on 7 October 2021. Retrieved 14 January 2024 .