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Chemical Compound Review

metformin     3-(diaminomethylidene)-1,1- dimethyl-guanidine

Synonyms: Fluamine, Fortamet, Glumetza, Dianben, Flumamine, ...
 
 
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Disease relevance of metformin

 

Psychiatry related information on metformin

 

High impact information on metformin

 

Chemical compound and disease context of metformin

 

Biological context of metformin

 

Anatomical context of metformin

 

Associations of metformin with other chemical compounds

  • CONCLUSIONS: Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone [16].
  • BACKGROUND & AIMS: The biguanide drug metformin has recently been found to improve steatosis and liver damage in animal models and in humans with nonalcoholic steatohepatitis [26].
  • The effect of metformin or rosiglitazone monotherapy versus placebo on insulin signaling and gene expression in skeletal muscle of patients with newly diagnosed type 2 diabetes was determined [31].
  • These data demonstrate that, unlike glyburide, metformin provides cardioprotection against HG-induced abnormalities in myocyte relaxation, perhaps through tyrosine kinase-dependent changes in intracellular Ca2+ handling, independent of its insulin sensitizing action [32].
  • To determine whether improving S(I) in subjects with impaired glucose tolerance (IGT) was associated with decreased CD68 expression, IGT subjects were treated for 10 weeks with pioglitazone or metformin [33].
  • The insulin sensitivity index increased with metformin but did not change with Diane(35) Diario [34].
  • At 6 and 12 months after treatment suspension, in the metformin group, insulin sensitivity index significantly (P < 0.05) worsened in comparison with that observed at baseline and during treatment and with that observed in the placebo and control groups [35].
  • Metformin dose-dependently suppressed IL-1beta-induced IL-8 production, cAMP-induced mRNA expression and aromatase activity, and 5-bromo-2'-deoxyuridine incorporation in ESCs [36].
  • In therapy naïve women, we found no evidence of a difference in live birth rate when comparing metformin with clomifene citrate (CC) [relative risks (RR) 0.73; 95% confidence interval (CI) 0.51-1.1] or comparing metformin plus CC with CC (RR 1.0; 95% CI 0.82-1.3) [37].
  • The inhibition of metformin renal tubular secretion by cimetidine also appeared to be dependent on this mutation [38].
  • The results presented herein show that the addition of metformin to paclitaxel leads to quantitative potentialization of molecular signaling through AMPK and a subsequent potent inhibition of the mTOR signaling pathway [39].
 

Gene context of metformin

 

Analytical, diagnostic and therapeutic context of metformin

References

  1. Lactic acidosis in patients with diabetes treated with metformin. Misbin, R.I., Green, L., Stadel, B.V., Gueriguian, J.L., Gubbi, A., Fleming, G.A. N. Engl. J. Med. (1998) [Pubmed]
  2. Efficacy of metformin in non-insulin-dependent diabetes mellitus. Gueriguian, J., Green, L., Misbin, R.I., Stadel, B., Fleming, G.A. N. Engl. J. Med. (1996) [Pubmed]
  3. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. Inzucchi, S.E., Maggs, D.G., Spollett, G.R., Page, S.L., Rife, F.S., Walton, V., Shulman, G.I. N. Engl. J. Med. (1998) [Pubmed]
  4. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. Nestler, J.E., Jakubowicz, D.J. N. Engl. J. Med. (1996) [Pubmed]
  5. Metformin-induced hemolysis with jaundice. Lin, K.D., Lin, J.D., Juang, J.H. N. Engl. J. Med. (1998) [Pubmed]
  6. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Zakikhani, M., Dowling, R., Fantus, I.G., Sonenberg, N., Pollak, M. Cancer Res. (2006) [Pubmed]
  7. Metformin: a therapeutic opportunity in breast cancer. Gonzalez-Angulo, A.M., Meric-Bernstam, F. Clin. Cancer Res. (2010) [Pubmed]
  8. Metformin use is associated with better survival of diabetic patients with pancreatic cancer. Sadeghi, N., Abbruzzese, J.L., Yeung, S.C., Hassan, M., Li, D. Clin. Cancer Res. (2012) [Pubmed]
  9. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. Inzucchi, S.E. JAMA (2002) [Pubmed]
  10. Glycemic control in patients with type 2 diabetes mellitus switched from twice-daily immediate-release metformin to a once-daily extended-release formulation. Fujioka, K., Pans, M., Joyal, S. Clinical therapeutics. (2003) [Pubmed]
  11. Metformin therapy in a transgenic mouse model of Huntington's disease. Ma, T.C., Buescher, J.L., Oatis, B., Funk, J.A., Nash, A.J., Carrier, R.L., Hoyt, K.R. Neurosci. Lett. (2007) [Pubmed]
  12. The effect of metformin on hirsutism in polycystic ovary syndrome. Kelly, C.J., Gordon, D. Eur. J. Endocrinol. (2002) [Pubmed]
  13. Contra-indications to metformin therapy are largely disregarded. Holstein, A., Nahrwold, D., Hinze, S., Egberts, E.H. Diabet. Med. (1999) [Pubmed]
  14. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. Nestler, J.E., Jakubowicz, D.J., Evans, W.S., Pasquali, R. N. Engl. J. Med. (1998) [Pubmed]
  15. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., Gerich, J.E. N. Engl. J. Med. (1995) [Pubmed]
  16. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. DeFronzo, R.A., Goodman, A.M. N. Engl. J. Med. (1995) [Pubmed]
  17. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Lin, H.Z., Yang, S.Q., Chuckaree, C., Kuhajda, F., Ronnet, G., Diehl, A.M. Nat. Med. (2000) [Pubmed]
  18. Effects of metformin or gemfibrozil on the lipodystrophy of HIV-infected patients receiving protease inhibitors. Martínez, E., Domingo, P., Ribera, E., Milinkovic, A., Arroyo, J.A., Conget, I., Pérez-Cuevas, J.B., Casamitjana, R., de Lazzari, E., Bianchi, L., Montserrat, E., Roca, M., Burgos, R., Arnaiz, J.A., Gatell, J.M. Antivir. Ther. (Lond.) (2003) [Pubmed]
  19. Metformin prevents high-glucose-induced endothelial cell death through a mitochondrial permeability transition-dependent process. Detaille, D., Guigas, B., Chauvin, C., Batandier, C., Fontaine, E., Wiernsperger, N., Leverve, X. Diabetes (2005) [Pubmed]
  20. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Tiikkainen, M., Häkkinen, A.M., Korsheninnikova, E., Nyman, T., Mäkimattila, S., Yki-Järvinen, H. Diabetes (2004) [Pubmed]
  21. Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Kukidome, D., Nishikawa, T., Sonoda, K., Imoto, K., Fujisawa, K., Yano, M., Motoshima, H., Taguchi, T., Matsumura, T., Araki, E. Diabetes (2006) [Pubmed]
  22. Glycemic control with glyburide/metformin tablets in combination with rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial. Dailey, G.E., Noor, M.A., Park, J.S., Bruce, S., Fiedorek, F.T. Am. J. Med. (2004) [Pubmed]
  23. A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Klein, D.J., Cottingham, E.M., Sorter, M., Barton, B.A., Morrison, J.A. Am. J. Psychiatry (2006) [Pubmed]
  24. Insulin-lowering agents in the management of polycystic ovary syndrome. De Leo, V., la Marca, A., Petraglia, F. Endocr. Rev. (2003) [Pubmed]
  25. Metformin in the treatment of HIV lipodystrophy syndrome: A randomized controlled trial. Hadigan, C., Corcoran, C., Basgoz, N., Davis, B., Sax, P., Grinspoon, S. JAMA (2000) [Pubmed]
  26. Metformin prevents alcohol-induced liver injury in the mouse: Critical role of plasminogen activator inhibitor-1. Bergheim, I., Guo, L., Davis, M.A., Lambert, J.C., Beier, J.I., Duveau, I., Luyendyk, J.P., Roth, R.A., Arteel, G.E. Gastroenterology (2006) [Pubmed]
  27. Role of AMP-activated protein kinase in mechanism of metformin action. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M.F., Goodyear, L.J., Moller, D.E. J. Clin. Invest. (2001) [Pubmed]
  28. Plasminogen activator inhibitor-1 synthesis in the human hepatoma cell line Hep G2. Metformin inhibits the stimulating effect of insulin. Anfosso, F., Chomiki, N., Alessi, M.C., Vague, P., Juhan-Vague, I. J. Clin. Invest. (1993) [Pubmed]
  29. Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects. Ciaraldi, T.P., Kong, A.P., Chu, N.V., Kim, D.D., Baxi, S., Loviscach, M., Plodkowski, R., Reitz, R., Caulfield, M., Mudaliar, S., Henry, R.R. Diabetes (2002) [Pubmed]
  30. Association of Metformin's effect to increase insulin-stimulated glucose transport with potentiation of insulin-induced translocation of glucose transporters from intracellular pool to plasma membrane in rat adipocytes. Matthaei, S., Hamann, A., Klein, H.H., Benecke, H., Kreymann, G., Flier, J.S., Greten, H. Diabetes (1991) [Pubmed]
  31. Effects of metformin and rosiglitazone treatment on insulin signaling and glucose uptake in patients with newly diagnosed type 2 diabetes: a randomized controlled study. Karlsson, H.K., Hällsten, K., Björnholm, M., Tsuchida, H., Chibalin, A.V., Virtanen, K.A., Heinonen, O.J., Lönnqvist, F., Nuutila, P., Zierath, J.R. Diabetes (2005) [Pubmed]
  32. Metformin but not glyburide prevents high glucose-induced abnormalities in relaxation and intracellular Ca2+ transients in adult rat ventricular myocytes. Ren, J., Dominguez, L.J., Sowers, J.R., Davidoff, A.J. Diabetes (1999) [Pubmed]
  33. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Di Gregorio, G.B., Yao-Borengasser, A., Rasouli, N., Varma, V., Lu, T., Miles, L.M., Ranganathan, G., Peterson, C.A., McGehee, R.E., Kern, P.A. Diabetes (2005) [Pubmed]
  34. Comparison of ethinyl-estradiol plus cyproterone acetate versus metformin effects on classic metabolic cardiovascular risk factors in women with the polycystic ovary syndrome. Luque-Ramírez, M., Alvarez-Blasco, F., Botella-Carretero, J.I., Martínez-Bermejo, E., Lasunción, M.A., Escobar-Morreale, H.F. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  35. Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome. Palomba, S., Falbo, A., Russo, T., Manguso, F., Tolino, A., Zullo, F., De Feo, P., Orio, F. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  36. Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. Takemura, Y., Osuga, Y., Yoshino, O., Hasegawa, A., Hirata, T., Hirota, Y., Nose, E., Morimoto, C., Harada, M., Koga, K., Tajima, T., Yano, T., Taketani, Y. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  37. The role of metformin in polycystic ovary syndrome: a systematic review. Moll, E., van der Veen, F., van Wely, M. Hum. Reprod. Update (2007) [Pubmed]
  38. OCT2 polymorphisms and in-vivo renal functional consequence: studies with metformin and cimetidine. Wang, Z.J., Yin, O.Q., Tomlinson, B., Chow, M.S. Pharmacogenet. Genomics (2008) [Pubmed]
  39. Metformin Amplifies Chemotherapy-Induced AMPK Activation and Antitumoral Growth. Rocha, G.Z., Dias, M.M., Ropelle, E.R., Osório-Costa, F., Rossato, F.A., Vercesi, A.E., Saad, M.J., Carvalheira, J.B. Clin. Cancer Res. (2011) [Pubmed]
  40. Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin. Li, L., Mamputu, J.C., Wiernsperger, N., Renier, G. Diabetes (2005) [Pubmed]
  41. Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1. Al-Khalili, L., Forsgren, M., Kannisto, K., Zierath, J.R., Lönnqvist, F., Krook, A. Diabetologia (2005) [Pubmed]
  42. Metformin rapidly increases insulin receptor activation in human liver and signals preferentially through insulin-receptor substrate-2. Gunton, J.E., Delhanty, P.J., Takahashi, S., Baxter, R.C. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  43. Metformin therapy during puberty delays menarche, prolongs pubertal growth, and augments adult height: a randomized study in low-birth-weight girls with early-normal onset of puberty. Ibáñez, L., Valls, C., Ong, K., Dunger, D.B., de Zegher, F. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  44. Activation of 5'-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2. Um, J.H., Yang, S., Yamazaki, S., Kang, H., Viollet, B., Foretz, M., Chung, J.H. J. Biol. Chem. (2007) [Pubmed]
  45. Insulin receptor binding to monocytes, insulin secretion, and glucose tolerance following metformin treatment. Results of a double-blind cross-over study in type II diabetics. Prager, R., Schernthaner, G. Diabetes (1983) [Pubmed]
  46. Lipin Expression Is Attenuated in Adipose Tissue of Insulin-Resistant Human Subjects and Increases With Peroxisome Proliferator-Activated Receptor {gamma} Activation. Yao-Borengasser, A., Rasouli, N., Varma, V., Miles, L.M., Phanavanh, B., Starks, T.N., Phan, J., Spencer, H.J., McGehee, R.E., Reue, K., Kern, P.A. Diabetes (2006) [Pubmed]
  47. Metformin normalizes nonoxidative glucose metabolism in insulin-resistant normoglycemic first-degree relatives of patients with NIDDM. Widén, E.I., Eriksson, J.G., Groop, L.C. Diabetes (1992) [Pubmed]
 
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