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Tirzepatide adds an extra layer by also activating GIP receptors, giving it dual-hormone action

Around the same time, I think you remember that all of pharma was interested in obesity in the early 90s, everyone wanted to do diabetes as well as obesity, but they were separate teams and they all wanted to do small molecules, but it just happens to be so that the best idea we could find at that time was actually GLP-1, because we actually had clinical data relatively early that GLP-1 was a really good candidate as a treatment for diabetes because of the glucose sensitivity of the actions

Much of this evidence derives from animal models precisely because these integrated tissue-level responses cannot yet be recapitulated in vitro or in silico

Higher doses generally resulted in a higher rate of side effects