Why are we still in need for novel anti-obesity medications?

IF 13.6 Q1 HEALTH CARE SCIENCES & SERVICES Lancet Regional Health-Europe Pub Date : 2024-11-07 eCollection Date: 2024-12-01 DOI:10.1016/j.lanepe.2024.101098
Aaron Novikoff, Gerald Grandl, Xue Liu, Timo D Müller
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Abstract

From the pioneering moment in 1987 when the insulinotropic effect of glucagon-like peptide 1 (GLP-1) was first demonstrated in humans, to today's pharmaceutical gold rush for GLP-1-based treatments of obesity, the journey of GLP-1 pharmacology has been nothing short of extraordinary. The sequential conceptual developments of long-acting GLP-1 receptor (GLP-1R) mono-agonists, GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonists, and GLP-1R/GIPR/glucagon receptor (GcgR) triple agonists, have led to profound body weight-lowering capacities, with benefits that extend past obesity and towards obesity-associated diseases. The GLP-1R/GIPR dual-agonist tirzepatide has demonstrated a remarkable 23% body weight reduction in individuals with obesity over 72 weeks, eclipsing the average result achieved by certain types of bariatric surgery. Meanwhile, the GLP-1R/GIPR/GcgR triple-agonist retatrutide achieves similar body weight loss (∼25%) in just two-thirds of the time, potentially surpassing the efficacy of Roux-en-Y gastric bypass. These remarkable achievements rightfully raise the question whether and why there is still need for novel anti-obesity medications (AOMs) in the future.

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为什么我们仍然需要新的抗肥胖药物?
从1987年胰高血糖素样肽1 (GLP-1)的胰岛素促胰岛素作用首次在人体中被证实的开创性时刻,到今天以GLP-1为基础的肥胖治疗的制药淘金热,GLP-1药理学的历程可谓非凡。长效GLP-1受体(GLP-1R)单激动剂、GLP-1R/葡萄糖依赖性胰岛素性多肽受体(GIPR)双激动剂和GLP-1R/GIPR/胰高血糖素受体(GcgR)三重激动剂的概念相继发展,已经导致了深刻的体重降低能力,其益处延伸到过去的肥胖和肥胖相关疾病。GLP-1R/GIPR双激动剂替西帕肽在72周内可显著减轻肥胖患者23%的体重,超过了某些减肥手术的平均效果。同时,GLP-1R/GIPR/GcgR三重激动剂利特鲁肽仅在三分之二的时间内达到类似的体重减轻(约25%),可能超过Roux-en-Y胃旁路治疗的疗效。这些显著的成就理所当然地提出了一个问题,即未来是否以及为什么仍然需要新型抗肥胖药物(AOMs)。
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来源期刊
CiteScore
19.90
自引率
1.40%
发文量
260
审稿时长
9 weeks
期刊介绍: The Lancet Regional Health – Europe, a gold open access journal, is part of The Lancet's global effort to promote healthcare quality and accessibility worldwide. It focuses on advancing clinical practice and health policy in the European region to enhance health outcomes. The journal publishes high-quality original research advocating changes in clinical practice and health policy. It also includes reviews, commentaries, and opinion pieces on regional health topics, such as infection and disease prevention, healthy aging, and reducing health disparities.
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