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This multi-receptor activation enables: GLP-1R activation enhances glucose-dependent insulin secretion and reduces appetite through hypothalamic signaling GIPR activation (highest potency: EC50 0.0643 nM) promotes insulin secretion and modulates lipid metabolism GCGR activation (EC50 5.79 nM) increases energy expenditure and promotes hepatic fat oxidation Combined receptor engagement produces dose-dependent reductions in body weight and improvements in glycemic control Research demonstrates that GLP3s balanced activation across three receptors produces superior metabolic effects compared to single or dual agonists, with phase 2 trials showing up to 24.2% weight reduction in 48 weeks[2]

Metformin (N,N-dimethylbiguanide), a standard clinical drug for type 2 diabetes mellitus (T2DM) for over 60 years (Foretz et al., 2023), has been shown to have multiple biological effects beyond its hypoglycemic properties, such as antioxidant, anti-inflammatory, anti-tumor, anti-fibrotic, and antiviral activities (Petrasca et al., 2023