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The three moieties of Orforglipron, 2,2-dimethyl-tetrahydropyran, 3,5-dimethyl-4-fluoro-phenyl ring, and 4H-1,2,4-oxadiazol-5-one, are involved in engaging different segments of the GLP-1R ( FIGURE 15 On the other hand, the further development of Danuglipron (PF-06882,961), another orally active and potent small-molecule GLP-1RA, was discontinued recently due to reported adverse effects in Phase II clinical trials (Figure 16)

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