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GLP-1 GIP NASH Trial NEJM 2024 View on PubMed 2023 Diabetes Care Mechanism Glucagon Co-Agonism Amplifies GLP-1-Mediated Weight Loss via Brown Adipose Thermogenesis Finding: In mouse models, adding glucagon receptor agonism to GLP-1R agonism increased brown adipose tissue thermogenic gene expression (UCP1 +62%, PGC-1 +44%) and significantly amplified fat oxidation (+38%)

What began primarily as a treatment for type 2 diabetes has rapidly evolved, showcasing remarkable efficacy in weight management and hinting at much broader therapeutic potential

Acute or tissue-restricted APJ activation may be appropriate for cardiometabolic indications, whereas chronic systemic exposure may be unsuitable without biased or targeted agonists

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