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One review in 2017 that examined evidence from eight studies on the subject concluded that the wide variety of study designs, durations and small sample sizes made it difficult to reach a definitive conclusion

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Tirzepatide receptor pharmacology and predicted receptor occupancy GIPR-forward dual-incretin design, cAMP-biased GLP-1R with low beta-arrestin, GCGR negative control (EC50 329 nM)

These drugs have a lower systemic availability owing to extensive pre-systemic metabolism within the mucosa of the small intestine and the liver and are therefore known as topically acting even though they are taken orally[34]