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Careful titration plays an important role in tolerability

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Cloning of rat and human pancreatic GLP-1R cDNA documented that ligand-induced activation of a single unique GLP-1R increases intracellular levels of cAMP and also that GLP-1, but not glucagon, GIP, VIP, or secretin, activates GLP-1R [[360], [361], [362], [363], [364]]

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The 78-week PIONEER-3 study compared 1864 adults with diagnosed type-2 diabetes who received either metformin (with or without sulfonylurea), oral semaglutide in three different dosages, or sitagliptin (100 mg/d)