The promising preclinical findings with Acomplia (rimonabant) have been confirmed in a series of clinical studies, including pivotal phase III trials involving over 6,000 obese subjects that were carried out in both the US and Europe.

Two-year data from the phase III multicentre Rimonabant In Obesity (RIO) trials, which compared rimonabant at doses of 5mg and 20mg with placebo with respect to weight reduction and prevention of weight gain, showed that the positive results seen after a year’s treatment were sustained over the full two-year trial period.

Consistent with the one-year data, the results showed that overweight and obese patients taking rimonabant 20mg/d achieved significant reductions in body weight, waist circumference (an indicator of abdominal obesity) and improved lipid and glycaemic profiles compared with placebo recipients. Rimonabant also had a significant impact on metabolic CVD risk factors, greater than that expected by weight loss alone.

Efficacy and safety in long-term use is important feature of any antiobesity drug. Some potential antiobesity medications have proved effective in the first six months of treatment only to lose effectiveness as subjects develop resistance to treatment.

Data from the RIO trials suggest rimonabant is effective for maintaining weight loss for periods of at least two years. Long-term safety is also a major concern. In the US, the FDA generally requires two years of safety data before approving antiobesity drugs.

Results from the phase III RIO trial programme suggest rimonabant is well tolerated in long-term use. Among patients who were randomly assigned to continue their first-year treatment for a second year, 6.7%, 8.3% and 6.0% discontinued from the placebo, rimonabant 5mg and 20mg groups respectively.

The ongoing phase IIIb trial programme for rimonabant includes studies in patients with diabetes (SERENADE), dyslipidaemia (ADAGIO) and cardiovascular disease (STRADIVARIUS, AUDITOR, CRESCENDO).