AIMS: To compare the benefits and harms of naltrexone-bupropion using evidence from clinical study reports (CSRs). METHODS: We searched FDA and EMA websites, PubMed, and (May 2016) to identify pivotal trials; we then sent a freedom of information request to the EMA (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 CSR documents containing over 65 000 pages of data from four pivotal trials (n=4536). Significantly more participants who took naltrexone-bupropion achieved ≥5% reduction in body weight: RR=2.1 (1.35 to 3.28, P=0.001, GRADE=low, NNTB =5 (3 to 17); this represents a 2.53 kg (1.85 to 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 to 1.18, P=0.0004, GRADE=low, NNTH =12 (7 to 27); serious adverse events: RR=1.70 (1.38 to 2.1), P<0.00001, GRADE=moderate, NNTH =21 (13 to 38); and discontinuation because of adverse events: RR=1.92 (1.65 to 2.24), P<0.00001, GRADE=moderate, NNTD =9 (8 to 13). CONCLUSIONS: Naltrexone-bupropion significantly reduces body weight by a small amount but significantly increases the risk of adverse events. A rigorous process of post-marketing surveillance is required.

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Journal article


Br J Clin Pharmacol

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Naltrexone-bupropion, clinical study report, meta-analysis, obesity, systematic review