Benefits and Harms of Mysimba® (Naltrexone + Bupropion) in the Management of Overweight and Obesity: A Systematic Review and Meta-Analysis of Unpublished Clinical Study Reports
41 Pages Posted: 31 Dec 2018More...
Background: Naltrexone-bupropion (Mysimba®) is approved for treatment of obesity. However, the benefit-harm profile is unclear and there is evidence of incomplete outcome reporting in journal publications of clinical trials.
Methods: For this systematic review and meta-analysis we obtained full unabridged clinical study reports (CSRs) from four pivotal phase III trials used to gain marketing authorization from the European Medicines Agency. The primary outcomes were body weight, adverse events, and discontinuations because of adverse events. We used the Cochrane criteria to assess the risk of bias and the GRADE guidelines to rate the quality of the evidence.
Findings: We included four trials with 4536 participants. Trial duration ranged from six to 12 months. Significantly more participants who took Mysimba® achieved ≥5% reduction in body weight (RR = 2∙1, 95% CI 2∙09 to 1∙35 P=0∙001, GRADE=low). The effect of Mysimba® on other cardiovascular risk profiles was unclear because of incomplete reporting of outcomes data. Mysimba® significantly increased the risk of adverse events (RR = 1∙11, 95% CI 1∙05 to 1∙18, P = 0∙0004, GRADE=low), serious adverse events (RR = 1∙70, 95% CI 1∙38 to 2∙1, P<0.00001, GRADE=moderate), and the risk of discontinuation because of adverse events (RR = 1∙92, 95% CI 1∙65 to 2∙24, P<0.00001, GRADE=moderate). We observed similar effect estimates for harms when we analysed adverse events classified by trial investigators as related or possibly related to interventions. Discontinuation rates were 42-47% across the four studies.
Interpretation: Mysimba® reduces body weight by small amounts and increases the risk of harms. Drop-out rates were high and the cardiovascular benefits of Mysimba® are unknown.
Funding Statement: This research was funded by the National Institute for Health Research School for Primary Care Research (NIHR-SPCR) (Project No: 390) as part of the Evidence Synthesis Working Group (ESWG) collaboration.
Declaration of Interests: IJO, JL, KRM and CJH report funding from the National Institute of Health Research, School for Primary Care Research (NIHR-SPCR) as part of the Evidence Synthesis Working Group (ESWG Project No: 390) to conduct independent research, including systematic reviews. CJH has received expenses from the WHO, FDA, and holds grant funding from the NIHR, the NIHR School of Primary Care Research, The Wellcome Trust and the WHO. He has received financial remuneration from an asbestos case. He has also received income from the publication of a series of toolkit books published by Blackwells. On occasion, he receives expenses for teaching EBM and is also paid for his GP work in NHS out of hours. CEBM jointly runs the EvidenceLive Conference with the BMJ and the Overdiagnosis Conference with some international partners which are based on a non-profit making model. JL and JKA have no interests to disclose.
Ethics Approval Statement: PROSPERO registration number: CRD42018086618.
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