Mixed Benefits Found for Anti-Obesity Drugs


EDMONTON, Alberta, Nov. 16 -- A meta-analysis of 30 controlled studies with orlistat (Xenical, Alli), sibutramine (Meridia, Reductil), and rimonabant (Acomplia, Zimulti) found that many patients lose a little weight, but not many lose a lot.
Action Points
Explain to interested patients this study suggests that anti-obesity drugs may not produce major weight loss.
Explain that side effects are important considerations with these drugs and mean a particular drug is unsuitable for some individuals.
Note that the study combined the results of many previously published studies conducted with different methods, so the findings must be interpreted with caution.
Patients taking the drugs were more likely to lose weight than those taking placebo, but mean weight reduction in the trials was less than 5 kg, or less than 5% of mean total body weight, according to a team led by Raj Padwal, M.D., at the University of Edmonton. The meta-analysis was published in the online edition of the British Medical Journal.
Among the studies included in the analysis, 16 looked at orlistat (Xenical, Alli), 10 at sibutramine (Meridia, Reductil), and 4 at rimonabant (Acomplia, Zimulti). Studies were included in the analysis if they were double-blind, randomized, and placebo-controlled with a duration of at least one year.
Compared with placebo, orlistat reduced weight by 2.9 kg (95% CI: 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (95% CI: 3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (95% CI: 4.2 kg to 5.3 kg).
Whether weight loss resulting from these drugs affects the incidence or severity of other obesity-related conditions, such as heart disease, remains largely uncertain.
"We found no data on the effect of these agents on mortality or cardiovascular morbidity," the researchers wrote.
However, they did find some evidence that orlistat may forestall type 2 diabetes. In the sole four-year trial included in the analysis, the incidence of type 2 diabetes was 6.2% among patients on orlistat versus 9% in those on placebo. Four other studies of orlistat indicated that fasting glucose levels were lower, although two other similarly designed studies found no difference.
One of the four rimonabant studies also showed reductions in blood sugar and glycated hemoglobin.
A high proportion -- averaging 30% to 40% -- of patients dropped out of the included studies. "Lack of adherence to treatment seems to be a major factor limiting the efficacy and effectiveness of anti-obesity drugs," Dr. Padwal's group wrote.
The researchers noted that 27 of the 30 studies were funded by manufacturers of the drugs, "which may increase the likelihood of positive results."
Gareth Williams, M.D., of the University of Bristol in the United Kingdom, said this was an important limiting factor in the analysis. "In the absence of any other data, these are the best there are," he said. But taking their biases into account, the modest efficacy found in most of the studies confirms that "none of them is a miracle drug," he said.
In a commentary that accompanied the Canadian group's paper, Dr. Williams said, "Clinical trials inevitably show anti-obesity drugs at their best, because the participants are relatively motivated and are supported by dedicated staff who reinforce lifestyle advice. ... Under real world conditions, [orlistat] might not fare so well because many people will not persevere with treatment for long enough to see benefits."
Dr. Williams recommended that physicians pay close attention to the side effect profiles of the various drugs and how they compare to patients' lifestyles and other conditions.
He also advised that rimonabant be avoided in patients with depression, in light of findings that it may have mood effects, including a possible increase in suicide attempts.
Earlier this year, sanofi-aventis withdrew its application for U.S. marketing of rimonabant, after an FDA advisory panel recommended against its approval, based on its psychiatric side effects.
The authors reported no external funding for the study. One of the co-authors disclosed financial relationships with unspecified makers of anti-obesity drugs.
Dr. Williams, the editorialist, reported financial relationships with Roche and GlaxoSmithKline (co-marketers of orlistat).Additional source: British Medical JournalSource reference: Rucker D, et al "Long-term pharmacotherapy for obesity and overweight: updated meta-analysis"British Medical Journal 2007; DOI: 10.1136/bmj.39385.413113.25.Additional source: British Medical JournalSource reference: Williams G, "Orlistat over the counter"British Medical Journal 2007; DOI: 10.1136/bmj.39385.347049.80.