Diabetes Research Centre, Department of Life and Health Sciences, Ulster University, Coleraine, Northern Ireland.
Expert Opin Pharmacother. 2023 Apr;24(5):587-597. doi: 10.1080/14656566.2023.2192865. Epub 2023 Mar 28.
Obesity is recognized as a major healthcare challenge. Following years of slow progress in discovery of safe, effective therapies for weight management, recent approval of the glucagon-like peptide 1 receptor (GLP-1R) mimetics, liraglutide and semaglutide, for obesity has generated considerable excitement. It is anticipated these agents will pave the way for application of tirzepatide, a highly effective glucose-dependent insulinotropic polypeptide receptor (GIPR), GLP-1R co-agonist, recently approved for management of type 2 diabetes mellitus.
Following promising weight loss in obese individuals in Phase III clinical trials, liraglutide and semaglutide were approved for weight management without diabetes. Tirzepatide has attained Fast Track designation for obesity management by the US Food and Drug Association. This narrative review summarizes experimental, preclinical, and clinical data for these agents and related GLP-1R/GIPR co-agonists, prioritizing clinical research published within the last 10 years where possible.
GLP-1R mimetics are often discontinued within 24 months meaning long-term application of these agents in obesity is questioned. Combined GIPR/GLP-1R agonism appears to induce fewer side effects, indicating GLP-1R/GIPR co-agonists may be more suitable for enduring obesity management. After years of debate, this GIPR-biased GLP-1R/GIPR co-agonist highlights the therapeutic promise of including GIPR modulation for diabetes and obesity therapy.
肥胖已被公认为是一个主要的医疗保健挑战。经过多年来在发现安全、有效的体重管理疗法方面进展缓慢，最近批准了胰高血糖素样肽 1 受体 (GLP-1R) 激动剂利拉鲁肽和司美格鲁肽用于肥胖症，这引发了相当大的兴奋。预计这些药物将为替西帕肽的应用铺平道路，替西帕肽是一种高效的葡萄糖依赖性胰岛素促分泌多肽受体 (GIPR)、GLP-1R 共激动剂，最近被批准用于 2 型糖尿病的治疗。
在 III 期临床试验中，肥胖个体的体重减轻令人鼓舞，利拉鲁肽和司美格鲁肽被批准用于无糖尿病的体重管理。替西帕肽已被美国食品和药物管理局 (FDA) 指定为肥胖管理的快速通道药物。这篇叙述性综述总结了这些药物和相关 GLP-1R/GIPR 共激动剂的实验、临床前和临床数据，优先考虑了在过去 10 年内发表的临床研究。
GLP-1R 激动剂通常在 24 个月内停止使用，这意味着这些药物在肥胖症中的长期应用受到质疑。联合 GIPR/GLP-1R 激动作用似乎引起的副作用较少，表明 GLP-1R/GIPR 共激动剂可能更适合长期肥胖症管理。经过多年的争论，这种 GIPR 偏向的 GLP-1R/GIPR 共激动剂突出了包括 GIPR 调节用于糖尿病和肥胖症治疗的治疗潜力。
