Hormonal multireceptor agonism for treatment of metabolic and non-metabolic conditions - potential value of glucagon receptor agonism

Hormonal multireceptor agonism for treatment of metabolic and non-metabolic conditions - potential value of glucagon receptor agonism | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 10 December 2025 V1 Latest version Share on Hormonal multireceptor agonism for treatment of metabolic and non-metabolic conditions - potential value of glucagon receptor agonism Authors : Ines Bosnic Kovacic , Kristijan Lipovac , Zrinka Planinic 0000-0001-8664-3338 , Aleksandra Dugandzic , Edvard Galic , and Zvonko Milicevic 0009-0002-8641-023X [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176536999.91447281/v1 213 views 238 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract A successful translation of glucagon-like peptide 1 (GLP-1) physiology into multiple pharmaceutical solutions has greatly improved our ability to treat conditions like Type 2 diabetes mellitus (T2DM), obesity, and obesity-associated comorbidities, and to prevent poor long-term health outcomes. This success has triggered increased interest in exploiting gut and pancreatic hormone physiology for the development of improved therapeutics. To build on the success of GLP-1 receptor mono-agonists, many research groups have focused on developing multi-receptor agonists with improved efficacy profiles. A dual gastrointestinal inhibitory peptide (GIP) receptor/GLP-1 receptor agonist, tirzepatide, has already shown benefits in the treatment of T2DM and obesity compared to GLP-1 receptor mono-agonists. Multiple other development programs are investigating the value of combining glucagon (GCG) receptor agonism with GLP-1 receptor agonism. The rationale is based on the physiological role of GCG in energy metabolism, including appetite suppression and, presumably, increased energy expenditure. These mechanisms are considered to enhance the effect of mono-agonism on adipose tissue mass in people with obesity. More recently, new data regarding the physiological roles of GCG beyond energy metabolism have emerged, potentially broadening the opportunities for utilizing its physiology in drug development strategies. In this review, we summarise findings from ongoing clinical development programs investigating drugs that activate the GCG receptor in combination with other entero-pancreatic hormone pathways. As several of these programs approach potential marketing authorisation, it is essential for the scientific and clinical communities to remain informed about new evidence and to prepare for the integration of these therapies into clinical practice. Supplementary Material File (hormonal multireceptor agonism for treatment of metabolic and non-metabolic conditions - potential value of glucagon addition (1) (1).docx) Download 124.78 KB Information & Authors Information Version history V1 Version 1 10 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Ines Bosnic Kovacic Clinical Hospital Sveti Duh View all articles by this author Kristijan Lipovac Clinical Hospital Sveti Duh View all articles by this author Zrinka Planinic 0000-0001-8664-3338 Clinical Hospital Sveti Duh View all articles by this author Aleksandra Dugandzic View all articles by this author Edvard Galic Clinical Hospital Sveti Duh View all articles by this author Zvonko Milicevic 0009-0002-8641-023X [email protected] Clinical Hospital Sveti Duh View all articles by this author Metrics & Citations Metrics Article Usage 213 views 238 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ines Bosnic Kovacic, Kristijan Lipovac, Zrinka Planinic, et al. Hormonal multireceptor agonism for treatment of metabolic and non-metabolic conditions - potential value of glucagon receptor agonism. Authorea . 10 December 2025. 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