Plecanatide

Plecanatide (Trulance) is linaclotide's close cousin — a related 16-amino-acid GC-C receptor agonist for the same constipation indications, but structurally modeled on the body's own uroguanylin rather than a bacterial toxin, and carrying the identical pediatric boxed warning.

A native-hormone-based design, not a bacterial one

Plecanatide is a 16-amino-acid peptide, structurally designed to mimic uroguanylin, an endogenous human hormone that activates the same guanylate cyclase-C (GC-C) receptor as linaclotide — a genuine, meaningful design difference, since linaclotide is instead based on a bacterial enterotoxin scaffold. Plecanatide is also pH-sensitive, preferentially activating in the mildly acidic environment of the proximal small intestine, which its developers argued more closely mimics how the body's own uroguanylin would normally act. The downstream mechanism — cGMP-driven chloride/bicarbonate secretion and faster transit — is the same as linaclotide's.

The approval and pivotal trials

The FDA approved plecanatide (as Trulance) on 19 January 2017 for chronic idiopathic constipation, based on Miner et al. (Am J Gastroenterol 2017, PMID 28169285): 1,394 patients, 12 weeks, a real placebo-controlled result supporting approval. An IBS-C indication followed in January 2018, based on two additional Phase 3 trials (Brenner et al., Am J Gastroenterol 2018, PMID 29545635).

The same pediatric boxed warning as linaclotide

Trulance carries the identical boxed warning as linaclotide: contraindicated in patients under 6, based on the same class of preclinical finding — single oral doses in young juvenile mice caused death from severe dehydration. The label also advises against use in patients 6 to under 18, since safety and efficacy haven't been established in that age range specifically.

Current status

Still marketed by Salix Pharmaceuticals (Bausch Health). No grey-market or wellness-adjacent presence.