Department of Medicine, University of Padova Medical School, Via Giustiniani 2, 35128 Padova, Italy.
Center for the Study and the Integrated Management of Obesity, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy; Department of Medicine, Internal Medicine 3,University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Pharmacol Res. 2021 Jul;169:105649. doi: 10.1016/j.phrs.2021.105649. Epub 2021 May 4.
Several pharmacological approaches to controlling body weight have been developed over the last decades, albeit with limited success. Currently available agents include centrally acting appetite suppressants and peripherally acting compounds. Efficacy and safety of these agents in the clinical setting require a difficult balance. Further strategies including multiagonists able to simultaneously target multiple actors involved in obesity initiation and expansion such as the glucagon receptor family are under investigation. The results of recent clinical trials are encouraging and highlight emerging compounds as potential game changers. In view of the rising prevalence of obesity and the associated burden of comorbidities worldwide, and compared with other areas of pharmacological intervention, we feel that the field of obesity has been affected by therapeutic inertia. Of note, obesity may also affect the response to concomitant medications such as low-dose aspirin. Lessons from withdrawn agents such as the cannabinoid receptor antagonist rimonabant include developing compounds with a more targeted action profile (i.e., central vs peripheral, or antagonist versus inverse agonist) as well as careful selection of patients based on individual risk factors. We anticipate that the expanding knowledge base and clinical testing will result in improved outcomes for patients with obesity in the near future.
过去几十年来，人们已经开发出了几种控制体重的药理学方法，但效果有限。目前可用的药物包括中枢作用的食欲抑制剂和外周作用的化合物。这些药物在临床环境中的疗效和安全性需要艰难的平衡。进一步的策略包括多激动剂，能够同时针对肥胖起始和扩张涉及的多个因素，如胰高血糖素受体家族。最近临床试验的结果令人鼓舞，并强调了新兴化合物作为潜在的游戏规则改变者。鉴于肥胖的全球流行率不断上升以及相关的合并症负担，与其他药物干预领域相比，我们认为肥胖领域受到了治疗惰性的影响。值得注意的是，肥胖还可能影响伴随药物（如低剂量阿司匹林）的反应。从已撤回的药物（如大麻素受体拮抗剂利莫那班）中吸取的经验教训包括开发具有更靶向作用谱的化合物（即中枢作用与外周作用，或拮抗剂与反向激动剂），以及根据个体危险因素仔细选择患者。我们预计，不断扩大的知识库和临床测试将在不久的将来为肥胖患者带来更好的治疗效果。
