2型糖尿病
医学
利拉鲁肽
非酒精性脂肪肝
胰高血糖素样肽1受体
脂肪性肝炎
肥胖
糖尿病
脂肪肝
胰高血糖素样肽-1
内科学
生物信息学
药理学
内分泌学
受体
疾病
兴奋剂
生物
作者
Ronald Goldenberg,Jeremy Gilbert,Priya Manjoo,Sue D. Pedersen,Vincent Woo,Julie A. Lovshin
摘要
Summary Type 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP‐1RAs and developing novel GLP‐1RA‐based co‐agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High‐dose GLP‐1RAs and multi‐hormonal strategies including GLP‐1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high‐dose GLP‐1RAs, unimolecular, and multimolecular GLP‐1R‐based co‐agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP‐1R‐based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide‐spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH.
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