A year ago at this time, millions of obese Americans were looking forward to FDA approval of diet drug rimonabant (Acomplia / Zimulti). That did not happen. In fact, rimonabant may never make it to market in the United States -- and the great diet hope for 2008 is Merck's diet drug taranabant.

Obese Americans eager to hear more about taranabant got a teaser Jan. 10th, but the generally encouraging report in the January issue of the journal Cell Metabolism was again based on results from a phase II trial and not the big phase III trial underway these past two years.

The news, in fact, was very similar to the report on phase II results that Merck presented at the annual scientific meeting of the Obesity Society back on Oct. 24th. In the journal article, researchers said study participants taking varying doses of taranabant lost 8 to 14 pounds over a 12-week period.

But the report did not provide any new insights on the huge outstanding question: Does taranabant have a better side-effect profile than rimonabant?

Both drugs target CB-1 receptors, but Acomplia -- which also produced impressive weight loss in trials -- failed to make it to the U.S. market last summer after FDA experts voiced concern over rimonabant's psychiatric side-effects including depression and suicidality?

Merck researchers said between one-fifth and one-third of patients in the phase II trial of taranabant experienced psychiatric adverse effects, including depressed mood, irritability, anger, mood swings, tearfulness, anxiety, insomnia, and nervousness.

But Dr. Steven Heymsfield, global director of scientific affairs, obesity, for Merck Research, said "no suicidal thoughts were reported" in the phase II taranabant study, though he conceded that the question had not been asked in a systemic way.

Presumably, there will be more and better information on side-effect issues when Merck reports on results of its phase III taranabant trial later this year. No date has yet been set for the first reports from this trial.

But clearly, Merck will have to provide information that better addresses the issue of depressive side-effects than was offered by Acomplia developer Sanofi-Aventis if it is to have any hope of obtaining approval of taranabant by the FDA.

The company still expects to submit taranabant for U.S. regulatory approval sometime in 2008.