Metformin Hydrochloride

Metformin Hydrochloride Chemical formula
Synonyms: (BANM, USAN, rINNM) Hidrocloruro de metformina; LA-6023 (metformin or metformin hydrochloride); Metformiinihydrokloridi; Metformin Hidroklorür; Metformin hydrochlorid; Metformine, chlorhydrate de; Metformin-hidroklorid; Metforminhydroklorid; Metformini hydrochloridum; Metformino hidrochloridas. 1,1-Dimethylbiguanide hydrochloride.
Cyrillic synonym: Метформина Гидрохлорид.

💊 Chemical information

Chemical formula: C4H11N5,HCl = 165.6.
CAS — 657-24-9 (metformin); 1115-70-4 (metformin hydrochloride).
ATC — A10BA02.
ATC Vet — QA10BA02.


In Chin., Eur., Jpn, and US.

Ph. Eur. 6.2

(Metformin Hydrochloride). White or almost white crystals. Freely soluble in water; slightly soluble in alcohol; practically insoluble in acetone and in dichloromethane.

USP 31

(Metformin Hydrochloride). A white crystalline powder. Freely soluble in water; slightly soluble in alcohol; practically insoluble in acetone and in dichloromethane.

💊 Adverse Effects, Treatment, and Precautions

Breast feeding.

Based on animal studies the UK and US licensed product information warns that metformin may be distributed into breast milk, and that the possible effects on the infant should be considered if women wish to breast feed while receiving the drug. However, a study in 7 breast-feeding women receiving metformin at a median dose of 1.5 g daily found the concentrations in milk to be about a third of those in maternal plasma, resulting in a mean calculated dose to the infants of 40 micrograms/kg daily. Blood samples were taken from 4 of the infants: metformin concentrations were undetectable in 2, and were very low (10 to 15% of maternal values) in the others. Given these results the authors considered that women receiving metformin need not be discouraged from breast feeding.1 Similar results from 3 other studies2,3 that included 13 women have provided further evidence that metformin is distributed into breast milk, that concentrations in milk are less than those in maternal plasma, and that breast-fed infants would be exposed to a very small percentage of the maternal dose. Six infants were breastfed with no adverse effects that could be attributed to metformin. A prospective study4 of weight, height, and motor-social development over 6 months, in infants of women taking metformin (1.5 to 2.55 g daily) for polycystic ovary syndrome, found no difference between 61 infants who were breast-fed and 50 who were formula-fed.
1. Hale TW, et al. Transfer of metformin into human milk. Diabetologia 2002; 45: 1509–14
2. Gardiner SJ, et al. Transfer of metformin into human milk. Clin Pharmacol Ther 2003; 73: 71–7
3. Briggs GG, et al. Excretion of metformin into breast milk and the effect on nursing infants. Obstet Gynecol 2005; 105: 1437–41
4. Glueck CJ, et al. Growth, motor, and social development in breast- and formula-fed infants of metformin-treated women with polycystic ovary syndrome. J Pediatr 2006; 148: 628–32.


For the view that metformin could be used with little risk of hypoglycaemia in fasting Muslim patients during Ramadan, and suggestions for modifying the timing of doses, see under Precautions of Insulin.


Insulin is generally preferred for treatment of diabetes during pregnancy. However, there are limited data to suggest that metformin does not increase the risk of congenital abnormalities1,2 and does not adversely affect pregnancy outcome in diabetic women.2 A controlled study comparing insulin with metformin in gestational diabetes is underway.3 The use of metformin to improve ovulation in polycystic ovary syndrome (PCOS) is increasing. There is growing evidence to suggest that metformin used before and during pregnancy in these women does not increase the risk of congenital abnormalities,1,4-6 and may reduce first trimester spontaneous abortion,4,6which is common in women with PCOS.
1. Gilbert C, et al. Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Fertil Steril 2006; 86: 658–63
2. Hughes RCE, Rowan JA. Pregnancy in women with type 2 diabetes: who takes metformin and what is the outcome? Diabet Med 2006; 23: 318–22
3. Brown FM, et al. Metformin in pregnancy: its time has not yet come. Diabetes Care 2006; 29: 485–6
4. Glueck CJ, et al. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod 2002; 17: 2858–64
5. Glueck CJ, et al. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Hum Reprod 2004; 19: 1323–30
6. Thatcher SS, Jackson EM. Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin. Fertil Steril 2006; 85: 1002–9.

💊 Pharmacokinetics

Metformin hydrochloride is slowly and incompletely absorbed from the gastrointestinal tract; the absolute bioavailability of a single 500-mg dose is reported to be about 50 to 60%, although this is reduced somewhat if taken with food. Once absorbed, protein binding in plasma is negligible; the drug is excreted unchanged in the urine. The plasma elimination half-life is reported to range from about 2 to 6 hours after oral doses. Metformin crosses the placenta and is distributed into breast milk in small amounts.
1. Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996; 30: 359–71
2. Sambol NC, et al. Pharmacokinetics and pharmacodynamics of metformin in healthy subjects and patients with noninsulin-dependent diabetes mellitus. J Clin Pharmacol 1996; 36: 1012–21
3. Charles B, et al. Population pharmacokinetics of metformin in late pregnancy. Ther Drug Monit 2006; 28: 67–72.

💊 Uses and Administration

Metformin hydrochloride is a biguanide antidiabetic. It is given orally in the treatment of type 2 diabetes mellitus, and is the drug of first choice in overweight patients. Initial dosage is 500 mg two or three times daily or 850 mg once or twice daily with or after meals, gradually increased if necessary, at intervals of at least 1 week, to 2 to 3 g daily; doses of 3 g daily are associated with an increased incidence of gastrointestinal adverse effects. Gastrointestinal effects are also common on beginning therapy, and the BNF recommends starting therapy more gradually with 500 mg at breakfast for at least 1 week, then increasing to 500 mg twice daily for at least 1 week, with further increases as required, up to a usual maximum of 2 g daily in 3 divided doses with meals. A modified-release preparation is also available, which is given in an initial dose of 500 mg once daily and may be increased in increments of 500 mg, at intervals of at least 1 week, to a maximum of 2 g once daily with the evening meal. If glycaemic control is not adequate the dose may be divided to give 1 g twice daily with meals. If doses above 2 g daily are required, they should be given as the standard preparation. For doses used in children and adolescents, see below. Metformin is also used as the chlorophenoxyacetate and as the embonate.
1. Dunn CJ, Peters DH. Metformin: a review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 1995; 49: 721–49
2. Anonymous. Metformin for non-insulin-dependent diabetes mellitus. Med Lett Drugs Ther 1995; 37: 41–2
3. Bailey CJ, Turner RC. Metformin. N Engl J Med 1996; 334: 574–9
4. Melchior WR, Jaber LA. Metformin: an antihyperglycemic agent for treatment of type II diabetes. Ann Pharmacother 1996; 30: 158–64
5. Davidson MB, Peters AL. An overview of metformin in the treatment of type 2 diabetes mellitus. Am J Med 1997; 102: 99–110
6. Klepser TB, Kelly MW. Metformin hydrochloride: an antihyperglycemic agent. Am J Health-Syst Pharm 1997; 54: 893–903. Correction. ibid.; 1335
7. Kirpichnikov D, et al. Metformin: an update. Ann Intern Med 2002; 137: 25–33
8. Hundal RS, Inzucchi SE. Metformin: new understandings, new uses. Drugs 2003; 63: 1879–94.


A review of the action of metformin1 considered that although a number of possible mechanisms have been suggested, the major action of metformin lay in increasing glucose transport across the cell membrane in skeletal muscle. There is also some evidence in vitro that it can inhibit the formation of advanced glycosylation end-products.2
1. Klip A, Leiter LA. Cellular mechanism of action of metformin. Diabetes Care 1990; 13: 696–704
2. Tanaka Y, et al. Inhibitory effect of metformin on formation of advanced glycation end products. Curr Ther Res 1997; 58: 693–7.

Administration in children.

In children aged 10 years and older with type 2 diabetes mellitus, oral metformin hydrochloride may be used in a starting dose of 500 mg or 850 mg once daily, or 500 mg twice daily, given with or after a meal. It may be gradually increased if needed, at intervals of at least 1 week, to a maximum of 2 g daily given in 2 or 3 divided doses. Modifiedrelease preparations are generally not licensed for use in children. Although rare, the incidence of type 2 diabetes is increasing in children and adolescents, related in part to the increase in obesity occurring particularly in westernised countries. A small placebocontrolled study1 of patients aged 10 to 17 years with type 2 diabetes found that metformin improved glycaemic control and that adverse effects were similar to those in adults. In obese children and adolescents with hyperinsulinaemia, who are at risk of developing type 2 diabetes, small studies2,3 of metformin use have reported improvements in body composition and fasting insulin concentrations. There has also been some interest in the use of metformin as an adjunct to insulin in adolescents with type 1 diabetes; improvements in glycaemic control4,5 and reductions in insulin doses4 have been reported.
1. Jones KL, et al. Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial. Diabetes Care 2002; 25: 89–94
2. Freemark M, Bursey D. The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Abstract: Pediatrics 2001; 107: 763–4. Full version: (accessed 25/06/07
3. Srinivasan S, et al. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. J Clin Endocrinol Metab 2006; 91: 2074–80
4. Hamilton J, et al. Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin resistance: a randomized controlled trial. Diabetes Care 2003; 26: 138–43
5. Särnblad S, et al. Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes: randomised placebo-controlled trial with aspects on insulin sensitivity. Eur J Endocrinol 2003; 149: 323–9.

Diabetes mellitus.

Results of the United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive blood glucose control with metformin reduces the risk of diabetic complications and death in overweight patients with type 2 diabetes.1The study also generated some concern regarding intensive therapy with metformin plus a sulfonylurea but this was not borne out on further analysis and such combinations are widely used. Metformin is also used with the thiazolidinediones,2-5 or with insulin6 in patients requiring combined or more intensive therapy. Metformin has also been investigated for the prevention of type 2 diabetes in patients at high risk. Although metformin treatment for an average 2.8 years reduced the incidence of type 2 diabetes by 31% in a study7 of patients with impaired glucose tolerance, intensive lifestyle modification was actually more effective (58% reduction). Lifestyle modification was also more effective than metformin in reducing cardiovascular risk factors8 and the development of the metabolic syndrome.9 The durability of these effects is unknown but follow-up of this study is ongoing. There is some interest in using oral hypoglycaemics as adjuncts to insulin therapy in patients with type 1 diabetes. Short-term results from small studies have suggested that metformin may be beneficial, in this context, in adolescents with pubertal insulin resistance (see also Administration in Children, above) and perhaps in adults who are overweight or otherwise at risk of reduced insulin sensitivity.10
1. UK Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–65
2. Fonseca V, et al. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA 2000; 283: 1695–1702. Correction. ibid.; 284: 1384
3. Einhorn D, et al. Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. Clin Ther 2000; 22: 1395–1409
4. Wellington K. Rosiglitazone/metformin. Drugs 2005; 65: 1581–92
5. Deeks ED, Scott LJ. Pioglitazone/metformin. Drugs 2006; 66: 1863–77
6. Avilés-Santa L, et al. Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999; 131: 182–88
7. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403
8. The Diabetes Prevention Program Research Group. Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the Diabetes Prevention Program. Diabetes Care 2005; 28: 888–94
9. Orchard TJ, et al. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med 2005; 142: 611–19
10. Jefferies CA, et al. Potential adjunctive therapies in adolescents with type 1 diabetes mellitus. Treat Endocrinol 2004; 3: 337–43.
Polycystic ovary syndrome . It has been suggested that hyperinsulinism may play a pathogenetic role in stimulating the abnormal androgen production from the ovary seen in women with polycystic ovary syndrome. Most early studies of metformin in PCOS were small, observational, and of short duration, with mixed results. Although there were reports of reduced insulin levels, increased insulin sensitivity, and improved androgen concentrations, other studies failed to confirm these effects.1 Later randomised studies were also small, but some were of longer duration. These reported weight reductions of obese patients,2 reductions in insulin levels2-4 and increased sensitivity,5 improved androgen and other hormonal measures,2,3,5 improved menstrual patterns,2,4,5 and reduced hirsutism,2 but again, not consistently. Metformin has also been reported to increase the rate of spontaneous ovulation,6,7 and may improve the outcome of IVF procedures.8 Combination of metformin with clomifene appeared to improve ovulatory response, compared with clomifene alone, in studies of women with PCOS,6,9 though there is also a report of no apparent benefit.10 Furthermore, 2 large, placebo-controlled studies have found that metformin, either alone or with clomifene, did not improve the rate of ovulation, pregnancy, or live births in women with polycystic ovary syndrome.11,12 Some consider that current evidence supports a trial of metformin in patients with anovulation, androgen excess, and vascular risk factors, but because of the lack of data on long-term safety such use should be supervised by an endocrinologist or a physician with suitable expertise.1
1. Norman RJ, et al. Metformin and intervention in polycystic ovary syndrome. Med J Aust 2001; 174: 580–3
2. Pasquali R, et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000; 85: 2767–74
3. Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17α activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996; 335: 617–23
4. Morin-Papunen LC, et al. Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab 2000; 85: 3161–8
5. Moghetti P, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab 2000; 85: 139–46
6. Nestler JE, et al. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998; 338: 1876–80
7. Fleming R, et al. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab 2002; 87: 569–74
8. Stadtmauer LA, et al. Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors. Fertil Steril 2001; 75: 505–9
9. Kocak M, et al. Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Fertil Steril 2002; 77: 101–6
10. Sturrock NDC, et al. Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice. Br J Clin Pharmacol 2002; 53: 469–73
11. Moll E, et al. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. Abridged version: BMJ 2006; 332: 1485–8. Full version: reprint/332/7556/1485 (accessed 17/06/08) Correction available at: (accessed 17/06/08
12. Legro RS, et al. Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356: 551–66.

💊 Preparations

BP 2008: Metformin Tablets; USP 31: Glipizide and Metformin Hydrochloride Tablets; Glyburide and Metformin Hydrochloride Tablets; Metformin Hydrochloride Extended-Release Tablets; Metformin Hydrochloride Tablets.

Proprietary Preparations

Arg.: Baligluc; DBI AP; Diab Dos; Glucaminol; Glucogood; Glucophage; Islotin; Mectin; Medobis; Metforal; Metfori†; Oxemet; Redugluc; Austral.: Diabex; Diaformin; Glucohexal; Glucomet; Glucophage; Novomet; Austria: Clonarol; Desugar; Diabetex; Glucomin; Glucophage; Meglucon; Orabet†; Belg.: Glucophage; Metformax; Braz.: Diaformin; Dimefor; Formet†; Formyn; Glicefor; Glifage; Glucoformin; Metfordin†; Metformed; Teutoformin; Canad.: Glucophage; Glumetza; Glycon†; Chile: Diaglitab; Fintaxim; Glafornil; Glicenex; Glidanil; Glifortex; Glucophage; Hipoglucin; MenariniMetforal†; Cz.: Adimet; Diaphage; Glucomerck; Glucophage; Gluformin; Glumetsan; Langerin; Metfirex; Metfogamma; Siofor; Stadamet; Denm.: Glucophage; Orabet; Fin.: Diformin; Glucophage; Metforem; Oramet; Fr.: Diabamyl†; Glucophage; Stagid; Ger.: Biocos; Diabesin; Diabetase†; espaformin†; Glucobon; Glucophage; Juformin; Mediabet; Meglucon; Mescorit; Met; Metfodoc; Metfogamma; Metfor†; Metform†; MetSurrir; Siofor; Thiabet; Gr.: Glucofree; Glucophage; Metforil; Sukontrol; Hong Kong: CP-Metform; Diabetmin; Diaformin; Glucomet; Glucophage; Glumet; Guamet; Melbin; Hung.: Adimet; Gluformin; Maformin†; Meforal; Meglucon; Merckformin; Metfogamma; Metrivin†; Stadamet; India: Bigomet†; Emfor; Emnorm; Exermet; Formin†; Glumet; Glyciphage; Glyree M; Insumet; Metlong; Walaphage; X-Met; Indon.: Benofomin; Diabex; Eraphage; Forbetes; Formell; Gliformin; Glucofor; Glucophage; Glucotika; Gludepatic; Glufor; Glumin; Gradiab; Methormyl; Methpica; Metphar; Reglus; Tudiab; Zumamet; Irl.: Glucophage; Israel: Apophage; Glucomin; Glucophage; Glufor; Ital.: Glucophage; Metbay; Metfonorm; Metforal; Metiguanide; Jpn: Glycoran; Melbin; Malaysia: Diabemet†; Diabetmin; Glucomet; Glucophage; Glumet; Riomet; Xmet; Mex.: Aglumet; Anglucid; Apozemia; Dabex; Debeone; Dimefor; Dinamel; Ficonax; Forlucyl; Glucophage; Glunovag; Harbamind; Ifor; Meglubet; Melbexa; Mifelar; Pharmafet; Pre-Dial; Neth.: Diabex; Dianorm†; Finormet†; Glucophage; Glumeff; Niformina; Norw.: Glucophage; NZ: Glucomet; Glucophage†; Metomin; Philipp.: Diafat; Diazen; Euform; Fornidd; Glucare; Glucoform; Glucomed; Glucophage; Glumet; Glyformin; Horsulin; Humamet; I-Max; Insunex; Neoform; Nidcor; Sucranorm; Vimetrol; Xmet; Pol.: Glucophage†; Gluformin; Metfogamma; Metformax; Metifor; Siofor; Port.: Diabex; Glucophage; Mekoll; Risidon; Stagid; Rus.: Bagomet (Багомет); Formin (Формин Плив); Gliformin (Глиформин); Glucophage (Глюкофаж); Metfogamma (Метфогамма); Siofor (Сиофор); S.Afr.: Glucophage; Metforal; Singapore: Diabetmin; Diamin†; Glucophage; Glycomet; Glycoran†; Metforal; Spain: Dianben; Swed.: Glucophage; Switz.: Gluconormine; Glucophage; Metfin; Thai.: Ammiformin; Deson; Diamet; Formin; Gluco; Glucoles-500; Glucolyte; Glucomet†; Glucono; Glucophage; Gluformin; Glustress†; Glutabloc; Gluzolyte; Macromin†; Maformin; ME-F†; Meformed; Metfor; Metfron; Miformin; Pocophage; Poli-Formin; Prophage; Serformin; Siamformet; Turk.: Glifor; Glucophage; Gluformin; Glukofen; UAE: Dialon; UK: Glucophage; Metsol; USA: Fortamet; Glucophage; Glumetza; Riomet; Venez.: Diaformina; Dimefor†; Glafornil; Glucaminol; Glucofage. Multi-ingredient: Arg.: Avandamet; DBI Duo; Glucovance; Gludex Plus; Isloglib; Medobis G; Metformin Duo; Rosiglit-Met; Austral.: Avandamet; Glucovance; Belg.: Avandamet; Glucovance; Braz.: Glucovance; Starform; Canad.: Avandamet; Chile: Avandamet; Bi-Euglucon M; Diaglitab Plus; Glifortex-G; Glimet; Glucovance; Glukaut; Hipoglucin DA; Cz.: Avandamet; Competact; Eucreas; Glibomet; Glubrava; Glucovance; Denm.: Avandamet; Fin.: Avandamet; Fr.: Avandamet; Competact; Eucreas; Glucovance; Ger.: Avandamet; Gr.: Avandamet; Normell; Hong Kong: Avandamet; Glucovance; Hung.: Avandamet; India: Betaglim M†; Diaforte; Diaglip M; Exermet GM; Exermet GZ; Exermet P; Gliclamet; Glimiprex MF; GlimulinMF†; Glinil M; Glizid-M; Glycigon-M; Glycinorm M; Glygard M; Metaglez; PGlitz M; Piomed M; Piosafe MF; Roglin-M; Rosicon MF; Indon.: Avandamet; Glucovance; Irl.: Avandamet; Israel: Avandamet; Ital.: Avandamet; BiEuglucon M; Glibomet; Gliconorm; Glicorest; Glucomide; Pleiamide; Suguan M; Malaysia: Avandamet; Glucovance; Mex.: Apometglu; Avandamet; BiDizalon; Bi-Euglucon M; Bi-Pradia; Duo-Anglucid; Glimetal; Glucotec; Glucovance; Imalet; Insogen Plus; Insusym-Forte; Maviglin; Mellitron; Midapharma; Mifelar-C; Nadib-M; Norfaben M; Obinese; Sibet-C; Sil-Norboral; Wadil; Neth.: Avandamet; Glucovance; Norw.: Avandamet; Philipp.: Avandamet; Euglo Plus; Glucovance; Pol.: Avandamet; Port.: Avandamet; Competact; Glucovance; Rus.: Glibomet (Глибомет); Glucovance (Глюкован); S.Afr.: Glucovance; Singapore: Avandamet; Glucovance; Spain: Avandamet; Swed.: Avandamet; Switz.: Avandamet; Diabiformine; Glucovance; Thai.: Avandamet; UK: Avandamet; Competact; Eucreas; USA: Actoplus Met; Avandamet; Diofen; Glucovance; Glybofen; Janumet; Metaglip; Venez.: Avandamet; Bi-Euglucon; Diaformina Plus; Glucovance; Starform.
Published November 12, 2018.