An updated patent review of small molecule glucagon receptor antagonists (2020–2024)

In this observation period, innovation ownership shifted from pharmaceutical companies to academic institutions, which are emerging as key applicants for novel chemotypes. Such a significant shift reflects a broader divergence in innovation strategies, with academia increasingly exploring new chemotypes supported by deep learning and virtual screening, while companies focus on maintaining and optimizing established scaffolds. Furthermore, advances in structural and mechanistic studies have clarified ligand binding and biased signaling, informing the rational design of high-specificity, high-affinity GCGRAs. However, clinical investigations are warranted to assess whether these compounds can overcome current developmental bottlenecks, restore glucose homeostasis, and address safety concerns.