Effects of Metformin in a Non-Diabetic Patient Population

Summary

Metformin has a well-established safety profile and it has become clear that metformin has additional salutary effects, including anti-inflammatory, anti-aging, and anti-thrombotic properties. In this study, subjects will provide both venous blood samples and stool samples in addition to completing cognitive and physiologic testing at baseline, throughout a 90 day exposure to metformin, and 30 days following exposure to metformin in order to evaluate their immune, microbiome, cellular respiration, thrombotic, and inflammatory responses.

Timeline

Start

2019-01-22

Primary completion

2020-03-31

Completion

2020-03-31

Publications

• Background Randriamboavonjy V, Mann WA, Elgheznawy A, Popp R, Rogowski P, Dornauf I, Drose S, Fleming I. Metformin reduces hyper-reactivity of platelets from patients with polycystic ovary syndrome by improving mitochondrial integrity. Thromb Haemost. 2015 Aug 31;114(3):569-78. doi: 10.1160/TH14-09-0797. Epub 2015 May 21.
• Background Xin G, Wei Z, Ji C, Zheng H, Gu J, Ma L, Huang W, Morris-Natschke SL, Yeh JL, Zhang R, Qin C, Wen L, Xing Z, Cao Y, Xia Q, Lu Y, Li K, Niu H, Lee KH, Huang W. Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release. Sci Rep. 2016 Nov 2;6:36222. doi: 10.1038/srep36222.
• Background Alazawi W, Pirmadjid N, Lahiri R, Bhattacharya S. Inflammatory and Immune Responses to Surgery and Their Clinical Impact. Ann Surg. 2016 Jul;264(1):73-80. doi: 10.1097/SLA.0000000000001691.
• Background Kato M, Suzuki H, Murakami M, Akama M, Matsukawa S, Hashimoto Y. Elevated plasma levels of interleukin-6, interleukin-8, and granulocyte colony-stimulating factor during and after major abdominal surgery. J Clin Anesth. 1997 Jun;9(4):293-8. doi: 10.1016/s0952-8180(97)00006-8.
• Background Lin E, Calvano SE, Lowry SF. Inflammatory cytokines and cell response in surgery. Surgery. 2000 Feb;127(2):117-26. doi: 10.1067/msy.2000.101584.
• Background Jansson K, Redler B, Truedsson L, Magnuson A, Matthiessen P, Andersson M, Norgren L. Intraperitoneal cytokine response after major surgery: higher postoperative intraperitoneal versus systemic cytokine levels suggest the gastrointestinal tract as the major source of the postoperative inflammatory reaction. Am J Surg. 2004 Mar;187(3):372-7. doi: 10.1016/j.amjsurg.2003.12.019.
• Background Whelan SP, Zuckerbraun BS. Mitochondrial signaling: forwards, backwards, and in between. Oxid Med Cell Longev. 2013;2013:351613. doi: 10.1155/2013/351613. Epub 2013 May 29.
• Background Waltz P, Carchman EH, Young AC, Rao J, Rosengart MR, Kaczorowski D, Zuckerbraun BS. Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway. Autophagy. 2011 Mar;7(3):315-20. doi: 10.4161/auto.7.3.14044.
• Background Keel M, Schregenberger N, Steckholzer U, Ungethum U, Kenney J, Trentz O, Ertel W. Endotoxin tolerance after severe injury and its regulatory mechanisms. J Trauma. 1996 Sep;41(3):430-7; discussion 437-8. doi: 10.1097/00005373-199609000-00008.
• Background Loomba R, Lutchman G, Kleiner DE, Ricks M, Feld JJ, Borg BB, Modi A, Nagabhyru P, Sumner AE, Liang TJ, Hoofnagle JH. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2009 Jan;29(2):172-82. doi: 10.1111/j.1365-2036.2008.03869.x. Epub 2008 Oct 9.
• Background Hou X, Song J, Li XN, Zhang L, Wang X, Chen L, Shen YH. Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochem Biophys Res Commun. 2010 May 28;396(2):199-205. doi: 10.1016/j.bbrc.2010.04.017. Epub 2010 Apr 14.
• Background Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009 Jul 16;460(7253):392-5. doi: 10.1038/nature08221. Epub 2009 Jul 8.
• Background Algire C, Moiseeva O, Deschenes-Simard X, Amrein L, Petruccelli L, Birman E, Viollet B, Ferbeyre G, Pollak MN. Metformin reduces endogenous reactive oxygen species and associated DNA damage. Cancer Prev Res (Phila). 2012 Apr;5(4):536-43. doi: 10.1158/1940-6207.CAPR-11-0536. Epub 2012 Jan 18.
• Background Smith DL Jr, Elam CF Jr, Mattison JA, Lane MA, Roth GS, Ingram DK, Allison DB. Metformin supplementation and life span in Fischer-344 rats. J Gerontol A Biol Sci Med Sci. 2010 May;65(5):468-74. doi: 10.1093/gerona/glq033. Epub 2010 Mar 19.
• Background Pernicova I, Korbonits M. Metformin--mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014 Mar;10(3):143-56. doi: 10.1038/nrendo.2013.256. Epub 2014 Jan 7.

Drugs

Indications