Drug Class of Trulance (Plecanatide)
Trulance (plecanatide) is a guanylate cyclase-C (GC-C) agonist, a class of intestinal secretagogues that work by activating ion channels on enterocytes to increase fluid secretion into the intestinal lumen. 1
Mechanism of Action
Plecanatide is a 16-amino acid synthetic peptide analog of human uroguanylin that functions through a specific pH-dependent mechanism 2, 3:
- Binds to guanylate cyclase-C receptors on the luminal surface of intestinal epithelial cells 2
- Increases cyclic guanosine monophosphate (cGMP) concentrations, which triggers chloride and bicarbonate secretion into the intestinal lumen 2, 4
- Prevents sodium absorption, further enhancing water secretion 3
- Unique pH-dependent binding confines most activity to the proximal small bowel, distinguishing it from linaclotide which acts throughout the intestine 2, 3
Classification Within Secretagogues
The secretagogue class for constipation includes several distinct subclasses 2:
- Guanylate cyclase-C agonists: Plecanatide and linaclotide 2
- Chloride channel activators: Lubiprostone 2
- Sodium-hydrogen exchange inhibitors: Tenapanor 2
Plecanatide belongs specifically to the guanylate cyclase-C agonist subclass, sharing this mechanism with linaclotide but differing in its pH-dependent binding characteristics 2.
FDA-Approved Indications
Plecanatide is approved for two specific conditions in adults 1:
- Chronic idiopathic constipation (CIC) at 3 mg once daily 1
- Irritable bowel syndrome with constipation (IBS-C) at 3 mg once daily 1
Clinical Context and Positioning
The 2023 AGA-ACG guidelines provide a strong recommendation for plecanatide as a second-line agent when over-the-counter treatments fail for chronic idiopathic constipation, with moderate certainty of evidence 2. The British Society of Gastroenterology similarly recommends plecanatide as an efficacious second-line drug for IBS-C, though with weak recommendation strength and very low quality evidence 2.
The most common adverse effect is diarrhea, occurring in approximately 4.3% of patients, with treatment discontinuation due to diarrhea in only 1.2% 4. This diarrhea rate is comparable to linaclotide and tenapanor but higher than lubiprostone, which has a more favorable bowel side effect profile 5.