Journal of the Formosan Medical Association
Volume 105, Issue 9 , Pages 743-752, 2006

Safety and Effectiveness of Rosiglitazone in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

Received 18 October 2005; received in revised form 4 November 2005; accepted 7 March 2006.

Article Outline

Background/Purpose

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging in severity from steatosis to cirrhosis. Type 2 diabetes mellitus is a cause of primary NAFLD. Thiazolidinediones have been shown to enhance insulin sensitivity, improve glycemic control in type 2 diabetes patients and to improve the histologic markers of nonalcoholic steatohepatitis. This study aims to determine the safety and effectiveness of rosiglitazone in inadequately controlled type 2 diabetes patients with NAFLD.

Methods

Taiwanese type 2 diabetes patients with inadequate control on insulin secretagogues and metformin, with no history of significant alcohol ingestion, with mildly elevated serum aspartate amino-transferase (AST) and/or alanine aminotransferase (ALT) and a diagnosis of fatty liver determined by ultrasonography were enrolled. Patients were treated for 24 weeks with rosiglitazone, 4-8 mg daily. Primary endpoints were change in AST and ALT levels from baseline and reduction in A1C < 6.5%.

Results

Out of a total of 68 patients, 60 (88.2%) completed the study treatment without serious adverse events. Treatment in two (2.9%) patients was discontinued due to elevated AST or ALT levels to more than three times the upper limit of normal, and noncompliance or loss of follow-up in six (8.8%) patients. Of the 60 patients who completed the study treatment, mean fasting plasma glucose, A1C, fasting plasma insulin, mean ALT and homeostasis model assessment for insulin resistance were all significantly reduced. Normal AST and ALT levels were achieved and maintained for at least three consecutive measurements and through to the end of the study period in 20 (33.3%) patients. Weight increased by a mean of 2.6 ± 2.4 kg (p<0.001).

Conclusion

Rosiglitazone was reasonably well tolerated in patients with inadequately controlled type 2 diabetes and NAFLD. One-third of patients showed improved liver function after treatment.

Key Words:  nonalcoholic fatty liver disease , rosiglitazone , thiazolidinediones , type 2 diabetes

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References 

  1. Matteoni CA , Younossi ZM , Gramlich T , et al.   Nonalcoholic fatty liver disease: a spectrum of clinical pathological severity . Gastroenterology . 1999;116:1413–1419
  2. Festi D , Colecchia A , Sacco T , et al.   Hepatic steatosis in obese patients: clinical aspects and prognostic significance . Obes Rev . 2004;5:27–42
  3. Marchesini G , Brizi M , Morselli-Labate AM , et al.   Association of nonalcoholic fatty liver disease with insulin resistance . Am J Med . 1999;107:450–455
  4. Chitturi S , Abeygunasekera S , Farrell GC , et al.   NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome . Hepatology . 2002;35:373–379
  5. Marchesini G , Bugianesi E , Forlani G , et al.   Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome . Hepatology . 2003;37:917–923
  6. Salt WB . Nonalcoholic fatty liver disease (NAFLD): a comprehensive review . J Insur Med . 2004;36:27–41
  7. Phillips LS , Grunberger G , Miller E , et al.   Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes . Diabetes Care . 2001;24:308–315
  8. Lebovitz HE , Dole JF , Patwardhan R , et al.   Rosiglitazone monotherapy is effective in patients with type 2 diabetes . J Clin Endocrinol Metab . 2001;86:280–288
  9. Miyazaki Y , Mahankali A , Matsuda M , et al.   Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone . Diabetes Care . 2001;24:710–719
  10. Mayerson AB , Hundal RS , Dufour S , et al.   The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes . Diabetes . 2002;51:797–802
  11. Miyazaki Y , Mahankali A , Matsuda M , et al.   Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients . J Clin Endocrinol Metab . 2002;87:2784–2791
  12. Carey DG , Cowin GJ , Galloway GJ , et al.   Effect of rosiglita-zone on insulin sensitivity and body composition in type 2 diabetic patients . Obes Res . 2002;10:1008–1015
  13. Bajaj M , Suraamornkul S , Pratipanawatr T , et al.   Pioglita-zone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes . Diabetes . 2003;52:1364–1370
  14. Neuschwander-Terri BA , Brunt EM , Wehmeier KR , et al.   Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-r ligand rosiglitazone . Hepatology . 2003;38:1008–1017
  15. Caldwell SH , Hespenheide EE , Redick JA , et al.   A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis . Am J Gastroenterol . 2001;96:519–525
  16. Tolman KG , Chandramouli J . Hepatotoxicity of the thiazo-lidinediones . Clin Liver Dis . 2003;7:367–379
  17. Lebovitz HE , Kreider M , Freed MI . Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction . Diabetes Care . 2002;25:815–821
  18. Rubin CJ , Schneider RL . Pioglitazone liver enzyme profiles is similar in placebo in US controlled clinical trials . Diabetes . 2000;49:A123
  19. Promrat K , Lutchman G , Uwaifo GI , et al.   A pilot study of pioglitazone treatment for non alcoholic steatohepatitis . Hepatology . 2004;39:188–196
  20. Matthews DR , Hosker JP , Rudenski AS , et al.   Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentration in man . Diabetologia . 1985;28:412–419
  21. Dailey GE , Noor MA , Park JS , et al.   Glycemic control with glyburide/metformin tablets in combination with rosiglitazone in patients with type 2 diabetes: a randomized, double blind trial . Am J Med . 2004;116:223–229
  22. Day C , James O . Steatohepatitis: a tale of two “hits”? . Gastroenterology . 1998;114:842–845
  23. Marceau P , Biron S , Hould FS , et al.   Liver pathology and the metabolic syndrome X in severe obesity . J Clin Endocrinol Metab . 1999;84:1513–1517
  24. Pavo I , Jermendy G , Varkonyi TT , et al.   Effect of pioglita-zone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes . J Clin Endocrinol Metab . 2003;88:1637–1645
  25. Hanefeld M , Brunetti P , Schernthaner GH , et al.   One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes . Diabetes Care . 2004;27:141–147
  26. Aronoff S , Rosenblatt S , Braithwaite S , et al.   Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes . Diabetes Care . 2000;23:1605–1611
  27. Kipnes MS , Krosnick A , Rendell MS , et al.   Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study . Am J Med . 2001;111:10–17
  28. Einhorn D , Rendell M , Rosenzweig J , et al.   Pioglita-zone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study . Clin Ther . 2000;22:1395–1409
  29. Aljabri K , Kozak SE , Thompson DM . Addition of pioglita-zone or bedtime insulin to maximal doses of sulfonylurea and metformin in type 2 diabetes patients with poor glucose control: a prospective, randomized trial . Am J Med . 2004;116:230–235
  30. Miyazaki Y , Pipek R , Mandarino LJ , et al.   Tumor necrosis factor a and insulin resistance in obese type 2 diabetic patients . Int J Obesity . 2003;27:88–94
  31. Spiegelman BM . PPAR-?: adipogenic regulator and thia-zolidinedione receptor . Diabetes . 1998;47:507–514
  32. Tonelli J , Li W , Kishore P , et al.   Mechanism of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes . Diabetes . 2004;53:1621–1629
  33. Haffner SM , Greenberg AS , Weston WM , et al.   Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes melli-tus . Circulation . 2002;106:679–684
  34. Mohanty P , Aljada A , Ghanim H , et al.   Evidence for a potent antiinflammatory effect of rosiglitazone . J Clin Endocrinol Metab . 2004;89:2728–2735
  35. Natali A , Ferrannini E . Hypertension, insulin resistance, and the metabolic syndrome . Endocrinol Metab Clin North Am . 2004;33:417–429
  36. American Gastroenterological Association  . AGA technical review on nonalcoholic fatty liver disease . Gastroenterology . 2002;123:1705–1725
  37. Quinn SF , Gosink BB . Characteristic sonographic signs of hepatic infiltration . Am J Roentgenol . 1985;145:753–755
  38. Mulhall BP , Ong JP , Younossi ZM . Non-alcoholic fatty liver disease: an overview . J Gastroenterol Hepatol . 2002;17:1136–1143

PII: S0929-6646(09)60202-3

doi:10.1016/S0929-6646(09)60202-3

Journal of the Formosan Medical Association
Volume 105, Issue 9 , Pages 743-752, 2006

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