N-B was licensed for obesity management by the European Medicines Agency (EMA Mysimba) and the US Food and Drug Administration (FDA Contrave) in September and December 2014 respectively. 5 The combined effects of naltrexone and bupropion are thought to reduce food craving. Naltrexone acts by autoinhibition of pro-opiomelanocortin neurons in the hypothalamus, while bupropion is thought to increase the actions of dopamine at specific sites in the brain. Naltrexone–bupropion (N-B) is a combination formulation used as treatment option for long-term management of overweight and obesity, in addition to exercise and a reduced-calorie diet. 4 More recently, combination therapies that act via central pathways have been developed these are now being licensed by drug regulatory authorities for clinical use. Most of them have central mechanisms of action and many have been withdrawn from the market because of unfavourable benefit–harm profiles. Several drugs have been licensed for the management of overweight and obesity over the last 70 years.
2 Cost-effective strategies to tackle this are urgently needed. 1 In 2016, there were over 1.9 billion overweight adults globally, of whom 650 million were obese. The prevalence of overweight and obesity continues to increase, and they have become major public health challenges. A rigorous process of postmarketing surveillance is required. Naltrexone–bupropion significantly reduces body weight by a small amount but significantly increases the risk of adverse events. 00001, GRADE = moderate, NNT to discontinue treatment = 9 8–13). 00001, GRADE = moderate, NNT to harm = 21 13–38) and discontinuation because of adverse events: RR = 1.92 (1.65–2.24, P <. Naltrexone–bupropion significantly increased the risk of adverse events: RR = 1.11 (1.05–1.18, P =. 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. 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. 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 =. 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). We used a random-effects model for meta-analyses.
We assessed the risks of bias using the Cochrane criteria, and the quality of the evidence using GRADE. We included pivotal, phase III placebo-controlled trials. We searched Food and Drug Administration and European Medicines Agency websites, PubMed, and (May 2016) to identify pivotal trials we then sent a freedom of information request to the European Medicines Agency (July 2016). To compare the benefits and harms of naltrexone–bupropion using evidence from clinical study reports.
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