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Orforglipron is under assessment for the management of obesity and T2D and may provide a competitive alternative to oral semaglutide, with less burdensome administration, as it does not require to be taken at a fasting state [24]

GLP-1 Receptor Activation Metabolic Regulation GLP2 activates GLP-1 receptors with lower potency than endogenous GLP-1 but demonstrates biased signaling properties: Preferential cAMP pathway activation over beta-arrestin recruitment, which may enhance insulin secretory responses Suppression of inappropriately elevated glucagon secretion during hyperglycemia Reduced GLP-1 receptor internalization compared to native GLP-1, potentially extending signaling duration Contribution to glucose-dependent insulin secretion complementary to GIP receptor effects Research in isolated pancreatic islets demonstrated that GLP2s insulinotropic actions depend on GIP receptor presence, with the biased GLP-1 receptor signaling providing synergistic enhancement

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