Naltrexone‐bupropion (Mysimba®) in management of obesity: A systematic review and meta‐analysis of unpublished clinical study reports

Aims: To compare the benefits and harms of naltrexone–bupropion using evidence from clinical study reports. Methods: We searched Food and Drug Administration and European Medicines Agency websites, PubMed, and Clinicaltrials.gov (May 2016) to identify pivotal trials; we then sent a freedom of information request to the European Medicines Agency (July 2016). We included pivotal, phase III placebo‐controlled trials. We assessed the risks of bias using the Cochrane criteria, and the quality of the evidence using GRADE. We used a random‐effects model for meta‐analyses. Results: Over a 27‐month period (July 2016 to August 2018), we received 31 batches of clinical study report documents containing over 65 000 pages of data from 4 pivotal trials (n = 4536). Significantly more participants who took naltrexone–bupropion achieved ≥5% reduction in body weight: risk ratio (RR) = 2.1 (95% confidence interval 1.35–3.28), P = .001, GRADE = low, number needed to treat (NNT) to benefit = 5 (3–17); this represents a 2.53 kg (1.85–3.21) reduction in baseline body weight compared with placebo. Naltrexone–bupropion had significantly beneficial effects on other cardiovascular risk factors; however, the true effect sizes for these are uncertain because of incomplete outcome data. Naltrexone–bupropion significantly increased the risk of adverse events: RR = 1.11 (1.05–1.18, P = .0004, GRADE = low, NNT to harm = 12 7–27); serious adverse events: RR = 1.70 (1.38–2.1, P Conclusions: Naltrexone–bupropion significantly reduces body weight by a small amount but significantly increases the risk of adverse events. A rigorous process of postmarketing surveillance is required.