Plecanatide

Plecanatide is built as an analog of uroguanylin, a natural peptide your intestine already makes to manage fluid balance. It activates guanylate cyclase-C receptors on the gut lining, which raises cyclic GMP inside those cells. That triggers chloride and bicarbonate secretion into the intestine and blocks sodium reabsorption, so water is drawn into the bowel, softening stool and speeding transit. One proposed difference from linaclotide is that its activity is more strongly switched on in the slightly acidic environment of the upper small intestine, which the manufacturer argues may shape where it acts, though this is a positioning claim more than a proven clinical advantage. Like other GC-C agonists it is minimally absorbed and works locally.