Japan's Takeda Pharmaceutical has dropped its investigational compound TAK-654, a follow-up to its widely-used diabetes drug Actos, after deciding that its efficacy and safety profile did not warrant further development.

TAK-654 was in Phase II clinical development in Japan, the USA and Europe. Based on a review of the preclinical and clinical data obtained to date, Takeda has concluded that it does not have a competitive profile compared to existing drugs.

TAK-654, like another Actos (pioglitzone) follow-up TAK-559, is a non-thiazolidinedione (TZD) insulin sensitizer. Both drugs were developed on the basis that they should be less likely to cause side effects such as weight gain and oedema than TZD drugs such as Actos.

TAK-559 reached Phase III development, but Takeda put the drug on ice in late 2004 after it was found to cause liver abnormalities in some patients. Other insulin sensitizers that have fallen by the wayside include Bristol-Myers Squibb's Pargluva (muraglitazar), AstraZeneca's tesaglitazar, Novo Nordisk/Dr Reddy's Laboratories' ragaglitazar, Japan Tobacco's reglitazar and Merck & Co's MK-767.