Rodriguez Natalie, Hartmann Phillipp
Department of Pediatrics, University of California San Diego, La Jolla, California.
Department of Pediatrics, University of California San Diego, La Jolla, California; Division of Gastroenterology, Hepatology and Nutrition, Rady Children's Hospital San Diego, San Diego, California.
Pharmacol Rev. 2025 Jul;77(4):100058. doi: 10.1016/j.pharmr.2025.100058. Epub 2025 Apr 16.
Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are estimated to affect 13% and one-third of adults worldwide, respectively. The novel antiobesity medications achieve marked bodyweight loss and improve associated metabolic conditions, including MASLD. This review summarizes the development and mode of action and available published data on the effectiveness of approved and potential (off-label) antiobesity products in the management of adult and pediatric obesity and MASLD. Additionally, their safety is highlighted. The most effective antiobesity drugs evaluated in double-blind, randomized controlled trials include semaglutide, tirzepatide, and retatrutide with up to 10.8%, 17.8%, and 22.1% placebo-subtracted bodyweight loss, respectively, in adults after 48-72 weeks. Semaglutide also reduces placebo-subtracted body mass index mean by up to 16.7% in adolescents with obesity after 68 weeks. Moreover, these novel drugs are highly effective in treating adults with MASLD. Semaglutide and tirzepatide resolve metabolic dysfunction-associated steatohepatitis (MASH) without worsening of fibrosis placebo-subtracted in 41% and 53% of patients, respectively, after 52-72 weeks. Semaglutide, tirzepatide, and retatrutide reduce hepatic fat on magnetic resonance imaging-proton density fat fraction placebo-subtracted by 41%, 47%, and 81%, respectively, after 48-72 weeks. Tirzepatide also decreases fibrosis without worsening of MASH placebo-subtracted in up to 25% of patients. However, no pediatric trials have been conducted to study these novel drugs in biopsy-proven MASLD. In conclusion, the novel antiobesity drugs are highly effective in obesity and MASLD. However, more biopsy-based clinical trials are required to determine the effectiveness of these medications in adult metabolic dysfunction-associated steatohepatitis-associated fibrosis and pediatric MASLD. SIGNIFICANCE STATEMENT: This work reviews the current antiobesity medications, their structure, mode of action, and effectiveness. These medications are revolutionizing the management of metabolic dysfunction-associated steatotic liver disease by significantly reducing hepatic steatosis, disease activity, and even liver fibrosis.
据估计，肥胖和代谢功能障碍相关脂肪性肝病（MASLD）分别影响全球13%的成年人和三分之一的成年人。新型抗肥胖药物可显著减轻体重，并改善包括MASLD在内的相关代谢状况。本综述总结了已批准和潜在（未获批准）的抗肥胖产品在治疗成人和儿童肥胖及MASLD方面的研发、作用方式和现有已发表的有效性数据。此外，还强调了它们的安全性。在双盲随机对照试验中评估的最有效的抗肥胖药物包括司美格鲁肽、替尔泊肽和瑞他鲁肽，在48 - 72周后，成人减去安慰剂后的体重减轻分别高达10.8%、17.8%和22.1%。司美格鲁肽在68周后还使肥胖青少年减去安慰剂后的体重指数平均降低了16.7%。此外，这些新型药物在治疗成人MASLD方面非常有效。司美格鲁肽和替尔泊肽分别在52 - 72周后使41%和53%的患者减去安慰剂后代谢功能障碍相关脂肪性肝炎（MASH）得到缓解且纤维化未加重。司美格鲁肽、替尔泊肽和瑞他鲁肽在48 - 72周后使磁共振成像 - 质子密度脂肪分数减去安慰剂后的肝脏脂肪分别减少了41%、47%和81%。替尔泊肽还使高达25%的患者减去安慰剂后纤维化减轻且MASH未加重。然而，尚未进行儿科试验来研究这些新型药物在经活检证实的MASLD中的疗效。总之，新型抗肥胖药物在肥胖和MASLD治疗中非常有效。然而，需要更多基于活检的临床试验来确定这些药物在成人代谢功能障碍相关脂肪性肝炎相关纤维化和儿童MASLD中的疗效。重要声明：本研究回顾了当前的抗肥胖药物、它们的结构、作用方式和有效性。这些药物正在彻底改变代谢功能障碍相关脂肪性肝病的治疗方式，通过显著减少肝脏脂肪变性、疾病活动甚至肝纤维化。
