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For drugs that are highly extracted by the liver, bypassing hepatic sites of elimination (eg, in hepatic cirrhosis with portosystemic shunting) will result in substantial increases in drug availability, whereas for drugs that are poorly extracted by the liver (for which the difference between entering and exiting drug concentration is small), shunting of blood past the liver will cause little change in availability

By activating these receptors, semaglutide may reduce the perceived reward value of alcohol and other substances

In the context of triple agonism, the insulin-stimulating effects of GLP-1R and GIPR activation counterbalance the glucagon receptors glucose-raising action

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Koutoulogenis et al