Plecanatide (Trulance): Uses, Evidence, and Side Effects

Chronic constipation and IBS-C can be frustrating to manage, and many patients want to understand what their prescribed therapy actually does before they start it. Plecanatide is an FDA-approved prescription peptide built to address both conditions through a specific gut receptor pathway.

Key takeaways

• Plecanatide is the active ingredient in Trulance, approved for adults with chronic idiopathic constipation and IBS-C.
• It works as a guanylate cyclase-C agonist, mimicking a natural gut signaling molecule.
• The label carries a boxed warning.
• At least 15 trials have studied plecanatide, including completed phase 2 and phase 3 work.
• FAERS reports are led by gastrointestinal effects, most often diarrhoea.

What Plecanatide Is

Plecanatide belongs to a drug class called guanylate cyclase-C (GC-C) agonists. It is structurally similar to uroguanylin, a signaling molecule the body produces naturally in the gut. Plecanatide and its active metabolite bind to GC-C receptors on the lining of the intestine. This binding raises levels of a messenger called cyclic GMP inside and outside intestinal cells, a change linked to downstream effects on bowel function.

What Plecanatide Is Approved For

Plecanatide is approved under the brand name Trulance for use in adults. The label covers two indications: chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). The prescribing information includes a boxed warning, which prescribers and patients should review carefully before use.

What the Evidence Shows

Plecanatide has been studied across at least 15 registered clinical trials. A completed phase 2 study examined efficacy and safety in adolescents aged 12 to under 18 with chronic idiopathic constipation. A completed phase 3 trial compared plecanatide with placebo for functional constipation. A separate postmarketing study also looked at plecanatide levels in the breast milk of lactating women taking Trulance.

Reported Side Effects

Reports submitted to FAERS are dominated by gastrointestinal complaints. Diarrhoea is the most frequently reported term, followed by nausea, constipation, and abdominal distension and pain. Fatigue and reports of the drug being ineffective also appear among the more common terms. These figures reflect the number of reports submitted, not confirmed incidence or a causal link to plecanatide.