Hepatic toxicity has not been associated with pioglitazone (Actos), said a
spokesperson for Takeda, the UK manufacturer, at the product’s launch on
November 7. Liver enzymes had been monitored continuously during both during
clinical trials and post-marketing surveillance of pioglitazone in the United
States, following concerns that the hepatic toxicity associated with troglitazone,
which resulted in its withdrawal in 1997, might be a class effect.
The summary of product characteristics for pioglitazone says that in clinical
trials, the incidence of elevations of alanine transaminase by greater than
three times the upper limit of normal was equal to that seen with placebo. The
SPC further notes that, although a causal relationship has not been established,
“isolated cases of elevated liver enzymes and hepatocellular dysfunction
have occurred in post-marketing experience”. Commenting on the adverse
effects of pioglitazone, Takeda said that the main side effect of treatment
was mild to moderate peripheral oedema. Small increases in weight were also
seen during trials, with most weight gain in the early period of treatment,
which then stabilised. So far, there had been no “head to head” comparison
between Smithkline Beecham’s rosiglitazone and pioglitazone, said Dr Gill
Hamilton (medical director, Takeda). In terms of using pioglitazone as monotherapy,
additional studies were ongoing.