Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
Front Endocrinol (Lausanne). 2021 Sep 8;12:735019. doi: 10.3389/fendo.2021.735019. eCollection 2021.
Obesity and Type 2 diabetes represent global health challenges, and there is an unmet need for long-lasting and effective pharmacotherapies. Although long-acting glucagon-like peptide-1 (GLP-1) analogues are now in routine use for diabetes and are now being utilised for obesity , the need for ever better treatments has driven the development of co-agonists, with the theoretical advantages of improved efficacy by targeting multiple pathways and reduced adverse effects. In this review, we highlight the past and present progress in our understanding and development of treatments based on GLP-1/glucagon co-agonism. We also reflect on the divergent effects of varying the GLP-1:glucagon activity and ratio in the context of pre-clinical and human clinical trial findings. In particular, the multiple metabolic actions of glucagon highlight the importance of understanding the contributions of individual hormone action to inform the safe, effective and tailored use of GLP-1/glucagon co-agonists to target weight loss and metabolic disease in the future.
肥胖症和 2 型糖尿病是全球性健康挑战，人们迫切需要长效且有效的药物疗法。尽管长效胰高血糖素样肽-1（GLP-1）类似物现已广泛用于治疗糖尿病，并开始用于肥胖症治疗，但为了寻求更好的治疗方法，人们开发了共激动剂，其理论优势在于通过靶向多种途径提高疗效和降低不良反应。在本文中，我们重点介绍了基于 GLP-1/胰高血糖素共激动作用的治疗方法的过去和现在的研究进展。我们还结合临床前和人体临床试验结果，反思了改变 GLP-1：胰高血糖素活性和比例的不同影响。特别是，胰高血糖素的多种代谢作用强调了了解单个激素作用的重要性，这有助于安全、有效地针对体重减轻和代谢疾病使用 GLP-1/胰高血糖素共激动剂，并为未来提供个体化治疗。
