Lazarus Ethan
Clinical Nutrition Center, Greenwood Village, CO, 80111, USA.
Obes Pillars. 2025 Feb 26;14:100170. doi: 10.1016/j.obpill.2025.100170. eCollection 2025 Jun.
Obesity is considered a chronic disease and is influenced by biological, environmental, and behavioral factors that can contribute to its progression. Although lifestyle changes are integral to treating obesity and maintaining a healthful weight, weight reduction from behavioral intervention alone is often insufficient because neurophysiologic factors may work against such changes in lifestyle and behavior. Research suggests that the mechanisms underlying food cravings and obesity overlap with dopaminergic signaling in the brain and pathways involved in addiction. As a result, patients who are differentially impacted by food cravings may have better outcomes with treatments targeting neural systems implicated in both homeostatic and hedonic food consumption or addictive behaviors.
In this clinical review, we describe the safety and efficacy data for the fixed-dose, extended-release combination of naltrexone and bupropion (NB-ER) compared with its monotherapy constituents (naltrexone and bupropion), as well as discuss the appropriate use of NB-ER to treat patients with obesity.
NB-ER is approved for the treatment of patients with obesity, with studies showing that patients can achieve significant weight reduction compared with placebo when treatment is combined with a reduced-calorie diet and increased physical activity. Across NB-ER phase 3 trials, responders to treatment had a mean body weight reduction of 11.7 % at 56 weeks. Of note, the unique combination of naltrexone, an opioid receptor antagonist, and bupropion, a norepinephrine-dopamine reuptake inhibitor associated with stimulating pro-opiomelanocortin cells (POMC), in NB-ER may work together to target POMC cells to prevent endogenous negative feedback, thereby decreasing appetite and improving weight-related outcomes.
Unlike monotherapy with its component drugs, NB-ER is optimized for the treatment of obesity. The appropriate use of NB-ER should consider the specific characteristics and adiposity-related complications of an individual.
肥胖被视为一种慢性疾病，受生物、环境和行为因素影响，这些因素会促使其发展。尽管生活方式改变对于治疗肥胖和维持健康体重至关重要，但仅靠行为干预来减轻体重往往并不够，因为神经生理因素可能会阻碍这种生活方式和行为的改变。研究表明，食物渴望和肥胖背后的机制与大脑中的多巴胺能信号传导以及成瘾相关通路存在重叠。因此，受食物渴望影响程度不同的患者，采用针对参与稳态和享乐性食物摄入或成瘾行为的神经系统的治疗方法，可能会取得更好的疗效。
在本临床综述中，我们描述了纳曲酮和安非他酮固定剂量缓释复方制剂（NB-ER）与其单一疗法成分（纳曲酮和安非他酮）相比的安全性和有效性数据，并讨论了NB-ER在治疗肥胖患者中的合理应用。
NB-ER已被批准用于治疗肥胖患者，研究表明，当与低热量饮食和增加体育活动相结合时，与安慰剂相比，患者可实现显著体重减轻。在NB-ER的3期试验中，治疗有反应者在56周时平均体重减轻了11.7%。值得注意的是，NB-ER中阿片受体拮抗剂纳曲酮与去甲肾上腺素-多巴胺再摄取抑制剂安非他酮（与刺激阿片促黑皮质素原细胞（POMC）相关）的独特组合，可能共同作用于POMC细胞，以防止内源性负反馈，从而降低食欲并改善与体重相关的结果。
与单一使用其成分药物不同，NB-ER在治疗肥胖方面进行了优化。NB-ER的合理使用应考虑个体的具体特征和与肥胖相关的并发症。
