Acta Diabetologica

, Volume 46, Issue 2, pp 113–118 | Cite as

The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease

Original Article


Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD). Several studies pointed out the possible role of increased leptin in NAFLD in humans. The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions. Thirty-four obese patients with newly diagnosed type 2 diabetes mellitus were prospectively followed for 6 months. All patients had ultrasonographic evidence of NAFLD at baseline. The patients were randomized into two groups: group 1 (n = 15) followed lifestyle changes only and group 2 (n = 19) received metformin (1,700 mg/day). At the end of treatment, BMI, WHR, HbA1c, fasting glucose, leptin, HOMA-IR, alanine aminotransferase values decreased in both groups. No significant difference in the end-points was observed between two groups. Only in group 2, LDL decreased and HDL increased significantly. Liver echogenity decreased significantly at the end of study in both groups. The percentage of patients who no longer had evidence of NAFLD was not significantly different between the groups (20% of patients on lifestyle intervention vs. 16% of patients on metformin). The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus. In addition, the effects of metformin on the variables were not found to be mediated by leptin.


Type 2 diabetes mellitus Nonalcoholic fatty liver disease Obesity Metformin Leptin 


  1. 1.
    Meigs JB (2000) Invited commentary: insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol 152:908–911PubMedCrossRefGoogle Scholar
  2. 2.
    Marchesini G, Bugianesi E, Forlani G et al (2003) Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37:917–923PubMedCrossRefGoogle Scholar
  3. 3.
    Marchesini G, Marzocchi R, Agostini F, Bugianesi E (2005) Nonalcoholic fatty liver disease and the metabolic syndrome. Curr Opin Lipidol 16:421–427PubMedCrossRefGoogle Scholar
  4. 4.
    Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 22:763–770CrossRefGoogle Scholar
  5. 5.
    Uygun A, Kadayifci A, Yesilova Z, Erdil A, Yaman H, Saka M, Deveci S, Bagci S, Gulsen M, Karaeren N, Dagalp K (2000) Serum leptin levels in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 95:3584–3589PubMedCrossRefGoogle Scholar
  6. 6.
    Hu ZW, Guo JW, Deng XL (2006) Association of serum leptin and insulin resistance with nonalcoholic fatty liver disease. Nan Fang Yi Ke Da Xue Bao 26:853–855Google Scholar
  7. 7.
    Kaplan LM (1998) Leptin, obesity and liver disease. Gastroenterology 115:997–1001PubMedCrossRefGoogle Scholar
  8. 8.
    Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N (2001) Metformin in non-alcoholic steatohepatitis. Lancet 358:893–894PubMedCrossRefGoogle Scholar
  9. 9.
    Uygun A, Kadayifci A, Isik AT, Ozgurtas T, Deveci S, Tuzun A, Yesilova Z, Gulsen M, Dagalp K (2004) Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 19:537–544PubMedCrossRefGoogle Scholar
  10. 10.
    Yajima Y, Ohta K, Narui T, Abe R, Suzuki H, Ohtsuki M (1983) Ultrasonographical diagnosis of fatty liver: significance of the liver-kidney contrast. Tohoku J Exp Med 139:43–50PubMedCrossRefGoogle Scholar
  11. 11.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRefGoogle Scholar
  12. 12.
    Marchesini G, Brizi M, Morselli Labate AM et al (1999) Association of non-alcoholic fatty liver disease to insulin resistance. Am J Med 107:450–455PubMedCrossRefGoogle Scholar
  13. 13.
    Caldwell SH, Argo CK, Al-Osaimi AM (2006) Therapy of NAFLD: insulin sensitizing agents. J Clin Gastroenterol 40(Suppl 1):S61–S66PubMedGoogle Scholar
  14. 14.
    Kirpichnikov D, McFarlane SI, Sowers JR (2002) Metformin: an update. Ann Intern Med 137:25–33PubMedGoogle Scholar
  15. 15.
    Lin HZ, Yang SQ, Chuckaree C, Kuhajda F, Ronnet G, Diehl AM (2000) Metformin reverses fatty liver disease in obese, leptin deficient mice. Nat Med 6:998–1003PubMedCrossRefGoogle Scholar
  16. 16.
    Duseja A, Das A, Dhiman RK, Chawla YK, Thumburu KT, Bhadada S, Bhansali A (2007) Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions. Ann Hepatol 6:222–226PubMedGoogle Scholar
  17. 17.
    Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M, Marchesini G (2005) A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 100:1082–1090PubMedCrossRefGoogle Scholar
  18. 18.
    Nair S, Diehl AM, Wiseman M, Farr GH Jr, Perrillo RP (2004) Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther 20:23–28PubMedCrossRefGoogle Scholar
  19. 19.
    Blaszyk H, Ferrentino N, Forsell S, Strader D, Lidofsky S (2005) A pilot study of metformin as treatment for nonalcoholic steatohepatitis. Gastroenterology 122:M1699Google Scholar
  20. 20.
    Akyuz F, Demir K, Ozdil S, Aksoy N, Poturoglu S, Ibrisim D, Kaymakoglu S, Besisik F, Boztas G, Cakaloglu Y, Mungan Z, Cevikbas U, Okten A (2007) The effects of rosiglitazone, metformin, and diet with exercise in nonalcoholic fatty liver disease. Dig Dis Sci 52:2359–2367PubMedCrossRefGoogle Scholar
  21. 21.
    Adams LA, Angulo P (2007) Role of liver biopsy and serum markers of liver fibrosis in non-alcoholic fatty liver disease. Clin Liver Dis 11:25–35PubMedCrossRefGoogle Scholar
  22. 22.
    Tasaka Y, Yanagisawa K, Iwamoto Y (1997) Human plasma leptin in obese subjects and diabetics. Endocr J 44:671–676PubMedCrossRefGoogle Scholar
  23. 23.
    Adamia N, Virsaladze D, Charkviani N, Skhirtladze M, Khutsishvili M (2007) Effect of metformin therapy on plasma adiponectin and leptin levels in obese and insulin resistant postmenopausal females with type 2 diabetes. Georgian Med News 145:52–55PubMedGoogle Scholar
  24. 24.
    Romualdi D, Campagna G, Selvaggi L Jr, Cento R, Proto C, Lanzone A, Guido M (2007) Metformin treatment does not affect total leptin levels and free leptin index in obese patients with polycystic ovary syndrome. Fertil Steril Jul 19 [Epub ahead of print]Google Scholar
  25. 25.
    Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE (1995) Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med 333:550–554PubMedCrossRefGoogle Scholar
  26. 26.
    Eriksson A, Attvall S, Bonnier M, Eriksson JW, Rosander B, Karlsson FA (2007) Short-term effects of metformin in type 2 diabetes. Diabetes Obes Metab 9:330–336PubMedCrossRefGoogle Scholar
  27. 27.
    Eguchi K, Tomizawa H, Ishikawa J, Hoshide S, Numao T, Fukuda T, Shimada K, Kario K (2007) Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes. Hypertens Res 30:23–30PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of Endocrinology and MetabolismFaculty of Medicine, Baskent UniversityAnkaraTurkey
  2. 2.Department of Endocrinology and MetabolismFaculty of Medicine, Hacettepe UniversityAnkaraTurkey

Personalised recommendations