Gastrointestinal Peptides

Plecanatide

Commonly used for

Constipation ReliefIBS-CMetabolic Health

What is it?

Plecanatide is a synthetic 16-amino acid peptide that is structurally similar to uroguanylin, a naturally occurring intestinal peptide involved in regulating fluid secretion. It activates guanylate cyclase-C (GC-C) receptors on the intestinal epithelium, increasing chloride and bicarbonate secretion into the intestinal lumen to improve bowel movements. Unlike many GI medications, plecanatide acts locally within the gastrointestinal tract with minimal systemic absorption.

Brand names: Trulance®

Mechanism of action: Guanylate cyclase-C (GC-C) receptor agonist; Increases intracellular cyclic GMP (cGMP); Stimulates chloride and bicarbonate secretion via CFTR; Increases intestinal fluid secretion; Accelerates intestinal transit; May reduce visceral pain signaling

What do people use it for?

Approved indications: Chronic Idiopathic Constipation (CIC); Irritable Bowel Syndrome with Constipation (IBS-C)

Proposed indications: Opioid-induced constipation; Functional constipation; Visceral hypersensitivity; Inflammatory bowel disease symptom management; Post-surgical constipation

How is it used? / Dosing

Administration: Oral tablet, can be taken with or without food — Once daily

How does it compare?

Compare with:

How well does it work? / Evidence

✓ Well-established

Evidence rating: Grade A — Multiple Phase III randomized controlled trials support efficacy and safety in chronic constipation and IBS-C.

Landmark trials: Phase III trials — Demonstrated significant improvement in complete spontaneous bowel movements, improvement in abdominal discomfort, and a good long-term safety profile.

Safety & side effects

Common side effects: Diarrhea, Abdominal distension, Flatulence, Nausea, Mild abdominal discomfort

Serious risks: Severe diarrhea leading to dehydration (rare); Contraindicated in young pediatric patients due to dehydration risk

Drug interactions: No clinically significant systemic drug interactions have been identified due to minimal absorption.

Monitoring: Improvement in bowel frequency, Stool consistency, Hydration status, Persistent diarrhea

Legal & regulatory status

Legal status: Prescription required. This is an FDA-approved medication available only through a licensed prescriber — dosing is determined by your prescriber based on your medical history and is not provided here.

Regulatory status: FDA Approved • EMA: Not currently approved

Who should avoid it?

Contraindications: Mechanical gastrointestinal obstruction; Children under 6 years of age (risk of severe dehydration); Hypersensitivity to plecanatide or formulation components

Pregnancy & breastfeeding: Limited human data. Use only if clinically indicated. Systemic exposure is minimal, suggesting low theoretical fetal exposure.

Research & references

Miner PB et al. (2017). A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation. Am J Gastroenterol. Brenner DM et al. (2018). Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials. Am J Gastroenterol.