CRD summary

This review concluded that, although rimonabant produced greater weight loss after 1 year than placebo, it increased the risk of psychiatric adverse events (mood disorders and anxiety). These conclusions are likely to be reliable, and the authors’ recommendations for further research into the safety of rimonabant and careful monitoring of patients appear appropriate.

Authors' objectives

To assess the efficacy and safety of rimonabant, a weight-loss drug.

Searching

MEDLINE (from the mid-1950s), EMBASE (from 1980), Web of Science (from 1945-54), Scopus (from 1966) and the Cochrane Library were searched up to November 2006; the search terms were stated. The reference lists of review articles and included studies were also checked. There were no language restrictions.

Study selection

Assessment of study quality

Two reviewers independently assessed trials using the Jadad instrument, which scores randomisation, blinding and withdrawals. Any disagreements were resolved by consensus.

Data extraction

Two reviewers extracted the data from studies in the review. All analyses were based on data reported as intention–to-treat. If a study contained phases for both weight loss and weight maintenance, the authors included only data from the weight loss phase. Mean differences were calculated for the mean weight change, standardised mean differences (SMDs) for the HADS score, and odds ratios (ORs) for dichotomous outcomes. Exact methods were used to calculate confidence intervals (CIs) for the ORs, owing to small numbers of events.

Methods of synthesis

Results of the review

Four randomised controlled trials (4,105 patients) were included in the review.

All four included trials were in the Rimonabant in Obesity (RIO) programme, which investigated the efficacy and safety of rimonabant for the treatment of obesity, diabetes and metabolic disorders in overweight and obese individuals. All were found to be of a high quality (about 5 on the Jadad scale). There was no evidence of a difference in the likelihood of completing a year’s treatment between rimonabant (59%) and placebo (58%) groups (OR 1.12, 95% CI: 0.99, 1.28).

Compared with placebo, rimonabant resulted in a greater weight loss of 4.7 kg (95% CI: 4.1, 5.3). Although all studies reported greater weight reductions with rimonabant than with placebo, there was evidence of heterogeneity regarding the magnitude of weight loss (I-squared 62.2%). Individuals receiving rimonabant were more likely to achieve at least a 10% weight loss (OR 5.1, 95% CI: 3.6, 7.3); there was also moderate heterogeneity for this outcome (I-squared 57.3%).

There was no significant difference between rimonabant and placebo in relation to depression, as measured on the HADS scale. However, the increase in anxiety score was significantly greater in the rimonabant group than in the placebo group (SMD 0.18, 95% CI: 0.07, 0.28); there was no evidence of heterogeneity (I-squared 0%).

Adverse events were more likely in the rimonabant group than in the placebo group; there was no evidence of heterogeneity between the studies. Patients receiving 20 mg/day rimonabant were more likely to report adverse events than those in the placebo group (OR 1.4, 95% CI: 1.1, 1.6). Serious adverse events were also more frequent in the rimonabant group than in the placebo group (OR 1.4, 95: CI: 1.2, 2.0), and patients were more likely to discontinue treatment due to depressive mood disorders (OR 2.5, 95% CI: 1.2, 5.1) and more likely to leave due to anxiety (OR 3.0, 95% CI: 1.1, 8.4).

The results of the meta-regression suggested that high concentrations of triglyceride at baseline might predict those who would suffer from depression on rimonabant, and that elderly people (unspecified) might be more likely than younger patients to have serious adverse events during treatment with rimonabant.

Authors' conclusions

Although rimonabant produced greater weight loss after 1 year than placebo, it increased the risk of psychiatric adverse events (i.e. mood disorders and anxiety).

CRD commentary

This review had clear inclusion criteria. A range of resources were searched with no language restrictions. The methods used to assess quality and extract the data were documented, but full details of the quality assessment were not reported for each study, although the authors did state that the studies were all rated as high quality. Details of the software used for the meta-analyses were reported, but not the actual method used (fixed or random), although the results appear consistent with random-effects models. The meta-analysis methods appear appropriate. However, since the meta-regression was based on only 4 studies and numerical results were not reported, these results should be treated with caution. The conclusions are likely to be reliable but it should be acknowledged that they are based on only 4 studies, all of which were sponsored by the manufacturer of rimonabant. The authors’ recommendations for further research and monitoring of practice appear appropriate.

Implications of the review for practice and research

Practice: The authors advised that, as the patients in trials were not suffering from depression at baseline, the risk of severe adverse events in clinical practice might actually be higher. They recommended that physicians remain alert to these adverse events.

Research: The authors suggested that the association between high triglyceride concentrations at baseline and the development of depression needs to be investigated, as does the link between older age and serious adverse events with rimonabant. The authors recommended an individual patient data meta-analysis to investigate safety concerns with rimonabant and to assess whether psychiatric adverse events are associated with the magnitude of weight loss.

Funding

University of Copenhagen, Center for Pharmacogenomics; Oak Foundation; H:S Research Foundation; Diabesity EC-FP6.

Bibliographic details

Christensen R, Kristensen P K, Bartels E M, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet 2007; 370: 1706-1713. [PubMed: 18022033]

Other publications of related interest

This additional published commentary may also be of interest.

Efficacy and safety of the weight-loss drug rimonabant [correspondence]. Lancet 2008;371:555-7.

Indexing Status

Subject indexing assigned by NLM

MeSH

Anti-Obesity Agents /adverse effects /therapeutic use; Anxiety Disorders /chemically induced; Depression /chemically induced; Double-Blind Method; Female; Humans; Male; Multicenter Studies as Topic; Obesity /drug therapy; Piperidines /adverse effects /therapeutic use; Pyrazoles /adverse effects /therapeutic use; Randomized Controlled Trials as Topic; Weight Loss /drug effects

AccessionNumber

12007008513

Database entry date

09/08/2008

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.