Welling Mila S, de Groot Cornelis J, Mohseni Mostafa, Meeusen Renate E H, Boon Mariëtte R, van Haelst Mieke M, van den Akker Erica L T, van Rossum Elisabeth F C
Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
EClinicalMedicine. 2024 Jul 3;74:102709. doi: 10.1016/j.eclinm.2024.102709. eCollection 2024 Aug.
Rare genetic obesity commonly features early-onset obesity, hyperphagia, and therapy-resistance to lifestyle interventions. Pharmacotherapy is often required to treat hyperphagia and induce weight loss. We describe clinical outcomes of glucagon-like peptide-1 analogue liraglutide or naltrexone-bupropion treatment in adults with molecularly confirmed genetic obesity (MCGO) or highly suspected for genetic obesity without definite diagnosis (HSGO).
We conducted a real-world cohort study at the Obesity Center CGG at Erasmus University Center, Rotterdam, Netherlands, between March 19, 2019, and August 14, 2023. All patients with MCGO and HSGO who were treated with either liraglutide or naltrexone-bupropion were included. Liraglutide 3 mg and naltrexone-bupropion were administered according to the manufacturer's protocol. Treatment evaluation occurred short-term, after 12 weeks on maximum or highest-tolerated dose, preceded by the 4-5 week dose escalation phase. Differences in anthropometrics, body composition, metabolic markers, self-reported appetite, eating behaviour, and quality of life (QoL) were evaluated.
Ninety-eight adults were included in the analysis: 23 patients with MCGO and 75 patients with HSGO, with median BMI of 42.0 kg/m (IQR 38.7-48.2) and 43.7 kg/m (IQR 38.0-48.7), respectively. After liraglutide treatment, median weight at evaluation significantly decreased compared to baseline in both groups: -4.7% (IQR -6.0 to -1.5) in patients with MCGO and -5.2% (IQR -8.1 to -3.5) in patients with HSGO. Additionally, improvements were observed in appetite, fat mass, fasting glucose, and HbA1c in both patients with MCGO and with HSGO. Patients with HSGO also reported significant improvements in several domains of QoL and eating behaviour. In patients with MCGO and HSGO treated with naltrexone-bupropion, mean weight at evaluation significantly differed from baseline: -5.2% ± 5.8 in patients with MCGO and -4.4% ± 4.7 in patients with HSGO. Appetite, fat mass, and waist circumference significantly decreased in both groups. Obesity-related comorbidities improved in significant proportions of patients treated with liraglutide or naltrexone-bupropion.
In conclusion, our short-term findings show potential of liraglutide and naltrexone-bupropion as treatment options for adults with (a clinical phenotype of) genetic obesity.
MB, EvdA, and EvR are supported by the Elisabeth Foundation, a non-profit foundation supporting academic obesity research.
罕见遗传性肥胖通常表现为早发性肥胖、食欲亢进以及对生活方式干预治疗有抵抗性。常常需要药物治疗来控制食欲亢进并减轻体重。我们描述了胰高血糖素样肽-1类似物利拉鲁肽或纳曲酮-安非他酮治疗经分子确诊的遗传性肥胖（MCGO）成人患者或高度怀疑遗传性肥胖但未明确诊断（HSGO）成人患者的临床结局。
2019年3月19日至2023年8月14日期间，我们在荷兰鹿特丹伊拉斯姆斯大学医学中心肥胖中心CGG开展了一项真实世界队列研究。纳入所有接受利拉鲁肽或纳曲酮-安非他酮治疗的MCGO和HSGO患者。利拉鲁肽3mg和纳曲酮-安非他酮按照药品说明书给药。在最大或最高耐受剂量治疗12周后进行短期治疗评估，此前有4-5周的剂量递增期。评估人体测量学、身体成分、代谢指标、自我报告的食欲、饮食行为和生活质量（QoL）的差异。
98例成人纳入分析：23例MCGO患者和75例HSGO患者，BMI中位数分别为42.0kg/m（IQR 38.7-48.2）和43.7kg/m（IQR 38.0-48.7）。利拉鲁肽治疗后，两组评估时的体重中位数相较于基线均显著下降：MCGO患者下降-4.7%（IQR -6.0至-1.5），HSGO患者下降-5.2%（IQR -8.1至-3.5）。此外，MCGO和HSGO患者的食欲、脂肪量、空腹血糖和糖化血红蛋白均有改善。HSGO患者在生活质量和饮食行为的多个方面也有显著改善。接受纳曲酮-安非他酮治疗的MCGO和HSGO患者，评估时的平均体重与基线相比有显著差异：MCGO患者为-5.2%±5.8，HSGO患者为-4.4%±4.7。两组患者的食欲、脂肪量和腰围均显著下降。接受利拉鲁肽或纳曲酮-安非他酮治疗的患者中，相当比例的肥胖相关合并症得到改善。
总之，我们的短期研究结果表明，利拉鲁肽和纳曲酮-安非他酮对患有（具有临床表型的）遗传性肥胖的成人具有治疗潜力。
MB、EvdA和EvR得到了伊丽莎白基金会的支持，该基金会是一个支持肥胖学术研究的非营利性基金会。
