Abstract
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 per se, 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.
Highlights
Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
Long-acting glucagonlike peptide-1 (GLP-1) analogues are in routine use for diabetes and are being utilised for obesity per se, 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
Obesity is a leading cause of global morbidity and death. It is a driver of multiple co-morbidities such as type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), hypertension, hypercholesterolaemia, cardiovascular disease and cancer [1]
Summary
ICV injections of OXM over 7 days led to food intake reduction and increased weight loss compared with saline treated controls [29]. Significant progress was made in understanding the potential use of the endogenous GLP-1/glucagon co-agonist OXM as a weight loss therapeutic in the early 2000s, evidence from various pre-clinical and human studies prior to this demonstrated the distinct mechanisms of weight loss afforded by these hormones.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
