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By identifying biological mechanisms rather than isolated genes, the analysis helps explain why some patients experience strong, durable benefit while others do not, supports quantitative prediction of response magnitude and tolerability, and provides a mechanistic foundation for more precise prescribing and drug-specific stratification as the GLP-1 class continues to expand

However, the GLP-1 [736] amide accounts for 80% of circulating GLP-1 ( FIGURE 1 Notably, the insulinotropic actions of circulating GLP-1 are facilitated through a two-domain binding interaction with GLP-1R (Figure 2), a structurally well-characterized prototypical class B GPCR, which recruits the G s -subunit of the heterotrimeric G-protein for cAMP-mediated downstream signaling, involving protein kinase A (PKA) and exchange protein activated by cAMP (EPAC), leading to insulin exocytosis

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