Diet drug guidelines issued

New obesity clinical guidelines, that doctors in the UK must follow as part of their national contracts with the National Health Services, have just been issued by NICE (the National Institute for Health and Clinical Excellence). They recommend rimonabant (Acomplia) for all ‘overweight’ and ‘obese’ people who can’t tolerate or haven’t had success with two other weight loss drugs.

Acomplia is the same drug that had been banned by the Food and Drug Administration in the United States over safety and efficacy concerns, and the European Medicines Agency had issued safety warnings concerning risks for mental health side effects. The safety and effectiveness problems raised in the four main randomized controlled clinical trials of Acomplia, and the postmarket adverse events being reported, were covered in detail here. A number of international scientific reviews have also raised concerns about the drug. Just weeks ago, it was announced that 5 deaths and 720 adverse events in the UK had been linked to Acomplia since it had been made available there in 2006.

Despite the international controversies, Acomplia has been given the go-head in Britain. Today’s final Guidance was not unexpected, however, as it followed the draft technology appraisal report, verbatim. In that report, reviewed in detail here, the NICE reviewers had said they’d been persuaded to reverse the earlier draft appraisal not recommending the drug, after they had received information from the manufacturer, Sanofi-Aventis, and stakeholder testimonies. The manufacturer’s evaluation of the effectiveness of rimonabant focused on those four clinical trials, which the NICE report said had shown a statistical association with a greater weight loss over a placebo (with diet and exercise) of 4.6 kg after 1 year of use. But, “after rimonabant treatment was stopped at 1 year,” the report stated, “there was a gradual increase in weight until there was no statistically significant difference from placebo at 2 years.”

Unresolved safety concerns; no proven, sustained clinical benefits for patients; and costs for the public that are likely to surpass all estimates, as described in the draft, all remained unanswered. Towards the back of the new guidance, NICE wrote that “future research is recommended to assess:

· the long-term clinical effectiveness and safety of rimonabant

· the short- and long-term effectiveness of rimonabant if continuation rules are imposed

· the effect of rimonabant on hard clinical endpoints, such as cardiovascular events, the development of diabetes and mortality

· the link between BMI changes and HRQoL [quality of life]

· the effectiveness of rimonabant in adults who have had an inadequate response to, are unable to tolerate or have a contraindication to orlistat and sibutramine.”

Yet, remarkably, with such fundamental scientific and medical issues remaining unresolved, NICE recommended its use and released this Guidance to be followed by NHS doctors and used with Obesity: guidance on the prevention, identification, assessment and management of overweight and obesity in adults and children (NICE clinical guideline 43). According to the Guidance:

Rimonabant, within its licensed indications, is recommended as an adjunct to diet and exercise for adults who are obese or overweight and who have had an inadequate response to, are intolerant of or are contraindicated to orlistat and sibutramine. Rimonabant treatment should be continued beyond 6 months only if the person has lost at least 5% of their initial body weight since starting rimonabant treatment. Rimonabant treatment should be discontinued if a person returns to their original weight while on rimonabant treatment. Rimonabant treatment should not be continued for longer than 2 years without a formal clinical assessment and discussion of the individual risks and benefits with the person receiving treatment.

NICE develops guidance for public health policy. Its Centre for Clinical Practice writes clinical guidelines, which it says “are recommendations, based on the best available evidence, on the appropriate treatment and care of people.”