Welling Mila S, van Rossum Elisabeth F C, van den Akker Erica L T
Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015 GD, The Netherlands.
Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015 GD, The Netherlands.
Endocr Rev. 2025 May 9;46(3):418-446. doi: 10.1210/endrev/bnaf004.
Lifestyle interventions are the cornerstone of obesity treatment. However, insufficient long-term effects are observed in patients with genetic obesity disorders, as their hyperphagia remains untreated. Hence, patients with genetic obesity often require additional pharmacotherapy to effectively manage and treat their hyperphagia and obesity. Recent advancements in antiobesity pharmacotherapy have expanded the range of available antiobesity medications (AOM). This includes the targeted AOM setmelanotide, approved for specific genetic obesity disorders, as well as nontargeted AOMs such as naltrexone-bupropion and glucagon-like peptide-1 analogues. Targeted AOMs have demonstrated significant weight loss, reduced obesity-related comorbidities, and improved hyperphagia and quality of life in patients with specific genetic obesity disorders. Small observational studies have shown that similar benefits from nontargeted AOMs or off-label pharmacotherapies can be achieved in patients with specific genetic obesity disorders, compared to common multifactorial obesity. In the future, novel and innovative pharmacotherapeutical options, including combination therapies and possibly gene therapy, will emerge, offering promising effects on body weight, hyperphagia, and, most importantly, quality of life for patients with a variety of genetic obesity disorders.
生活方式干预是肥胖症治疗的基石。然而，在患有遗传性肥胖症的患者中，观察到长期效果不足，因为他们的食欲亢进仍未得到治疗。因此，遗传性肥胖患者通常需要额外的药物治疗来有效控制和治疗他们的食欲亢进和肥胖症。抗肥胖药物治疗的最新进展扩大了可用抗肥胖药物（AOM）的范围。这包括已获批用于特定遗传性肥胖症的靶向AOM司美格鲁肽，以及非靶向AOM，如纳曲酮-安非他酮和胰高血糖素样肽-1类似物。靶向AOM已在患有特定遗传性肥胖症的患者中显示出显著的体重减轻、与肥胖相关的合并症减少，以及食欲亢进和生活质量改善。小型观察性研究表明，与常见的多因素肥胖症患者相比，患有特定遗传性肥胖症的患者使用非靶向AOM或超说明书药物治疗也能获得类似益处。未来，包括联合疗法以及可能的基因疗法在内的新型创新药物治疗选择将会出现，有望对各种遗传性肥胖症患者的体重、食欲亢进，以及最重要的生活质量产生积极影响。
