Body Weight Response With Disulfiram in Humans

Summary

Overweight and obesity due to food that exceeds the requirements is an increasingly common global problem. Lifestyle intervention and anorectic drugs result in minimal weight loss, which tends to be easily regained. In addition, drugs tend to have too many side effects and have had to be withdrawn from management schemes and even from the market. Disulfiram (Antabuse®️) is approved by the Food and Drug Administration against chronic alcohol addiction. In a mouse study, disulfiram prevented body weight gain and negated the adverse impact of an obesogenic diet on insulin; used properly it is a safe drug. Carrying out a testing-concept study with disulfiram will allow the establishment of guidelines on clinical studies focused on its use as an adjunct in the reduction and control of body weight.

Timeline

Start

2021-11-21

Primary completion

2022-01-31

Completion

2022-04-30

Publications

• Background Hall KD, Kahan S. Maintenance of Lost Weight and Long-Term Management of Obesity. Med Clin North Am. 2018 Jan;102(1):183-197. doi: 10.1016/j.mcna.2017.08.012.
• Results Chouchani ET, Kazak L, Spiegelman BM. New Advances in Adaptive Thermogenesis: UCP1 and Beyond. Cell Metab. 2019 Jan 8;29(1):27-37. doi: 10.1016/j.cmet.2018.11.002. Epub 2018 Nov 29.
• Results Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, Cohen P, Cinti S, Spiegelman BM. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest. 2011 Jan;121(1):96-105. doi: 10.1172/JCI44271. Epub 2010 Dec 1.
• Results Teijeiro A, Garrido A, Ferre A, Perna C, Djouder N. Inhibition of the IL-17A axis in adipocytes suppresses diet-induced obesity and metabolic disorders in mice. Nat Metab. 2021 Apr;3(4):496-512. doi: 10.1038/s42255-021-00371-1. Epub 2021 Apr 15.
• Results Bernier M, Mitchell SJ, Wahl D, Diaz A, Singh A, Seo W, Wang M, Ali A, Kaiser T, Price NL, Aon MA, Kim EY, Petr MA, Cai H, Warren A, Di Germanio C, Di Francesco A, Fishbein K, Guiterrez V, Harney D, Koay YC, Mach J, Enamorado IN, Pulpitel T, Wang Y, Zhang J, Zhang L, Spencer RG, Becker KG, Egan JM, Lakatta EG, O'Sullivan J, Larance M, LeCouteur DG, Cogger VC, Gao B, Fernandez-Hernando C, Cuervo AM, de Cabo R. Disulfiram Treatment Normalizes Body Weight in Obese Mice. Cell Metab. 2020 Aug 4;32(2):203-214.e4. doi: 10.1016/j.cmet.2020.04.019. Epub 2020 May 14.
• Results Bernier M, Harney D, Koay YC, Diaz A, Singh A, Wahl D, Pulpitel T, Ali A, Guiterrez V, Mitchell SJ, Kim EY, Mach J, Price NL, Aon MA, LeCouteur DG, Cogger VC, Fernandez-Hernando C, O'Sullivan J, Larance M, Cuervo AM, de Cabo R. Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome. NPJ Aging Mech Dis. 2020 Jul 21;6:8. doi: 10.1038/s41514-020-0046-6. eCollection 2020.

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