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The bulky A350 6.39b W and K351 6.40b A mutants almost abolished the maximal response (Emax) of GLP-1R-mediated cAMP accumulation in presence of compound 2, while V332 5.62b A, K346 6.35b A and L349 6.38b A mutants greatly elevated basal cAMP activities but significantly diminished the efficacy of the response upon stimulation by either compound 2 or GLP-1, suggesting these mutations affect the kink of TM6 required for receptor activation
Other therapeutic indications, including colitis, pediatric gastrointestinal disorders and inflammation of the intestinal mucosa, are currently under development
In practice, it seems better to tailor the choice to different patients, depending on the preference of the route of administration (oral vs injectable), the presence of intolerance or side-effects, and contraindications