The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Letter to the Editor

Editor, – The article 'Thiazolidinediones - mechanisms of action' (Aust Prescr 2004;27:67-70), states that 'hepatotoxicity does not seem to be associated with the other two compounds (pioglitazone, rosiglitazone)'. Although admittedly this may be referring to the rare but fatal cases of hepatotoxicity associated with troglitazone, it does seem somewhat at odds with the ADRAC Bulletin. This reported on 16 cases of hepatic adverse reactions including elevated liver function tests, jaundice, hepatitis and hepatocellular damage. Although it does add the rider that 'liver enzyme levels may be elevated with diabetes or obesity'.1

Derek Grubb
Pharmacy Department
Bunbury Regional Hospital
Bunbury, WA

Authors' comment

Dr J.R. Greenfield and Professor D.J. Chisholm, the authors of the article, comment:

In contrast to troglitazone, which was withdrawn because of rare but fatal liver failure, placebo-controlled trials show that the risk of liver function abnormalities (reversible elevations of alanine transferase greater than three times the upper limit of normal) in patients treated with pioglitazone or rosiglitazone is 0.2-0.3% and not different from placebo-treated patients.2 While rare case reports of hepatocellular injury and hepatic failure have been described in patients treated with these newer drugs3 , whether liver dysfunction can be definitively attributed to the thiazolidinedione has been challenged.4 As Mr Grubb acknowledges, liver function may be abnormal in patients with diabetes and/or obesity, particularly due to non-alcoholic fatty liver disease. Furthermore, liver function may actually improve following treatment with these drugs, due to a reduction in hepatic lipid content.5 As stated in our article, and the accompanying paper (Aust Prescr 2004;27:70-4), and by the Adverse Drug Reactions Advisory Committee, pharmacovigilance with periodic tests of liver function is recommended, despite the safety of pioglitazone and rosiglitazone.


  1. ADRAC. The glitazones - early experience. Aust Adv Drug React Bull 2003;22:6-7.
  2. Mudaliar S, Henry RR. New oral therapies for type 2 diabetes mellitus: The glitazones or insulin sensitizers. Annu Rev Med 2001;52:239-57.
  3. Tolman KG, Chandramouli J. Hepatotoxicity of the thiazolidinediones. Clin Liver Dis 2003;7:369-79.
  4. Freid J, Everitt D, Boscia J. Rosiglitazone and hepatic failure. Ann Intern Med 2000;132:164.
  5. Festi D, Colecchia A, Sacco T, Bondi M, Roda E, Marchesini G. Hepatic steatosis in obese patients: clinical aspects and prognostic significance. Obes Rev 2004;5:27-42.