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

Living with chronic constipation or IBS-C can mean daily discomfort and unpredictable bathroom habits. Plecanatide is an FDA-approved prescription medication designed to address both conditions by working directly in the gut.

Key takeaways

• Plecanatide is approved for chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) in adults.
• It works as a guanylate cyclase-C agonist, mimicking a natural gut hormone to promote fluid secretion.
• The drug carries a boxed warning on its label.
• At least 15 clinical trials have investigated plecanatide, including completed Phase 2 and Phase 3 studies.
• The most frequently reported side effect in postmarket safety data is diarrhoea, followed by nausea and constipation.

What Plecanatide Is

Plecanatide, sold under the brand name Trulance, belongs to a drug class called guanylate cyclase-C (GC-C) agonists. It is a structural analog of uroguanylin, a hormone the body produces naturally in the intestines. Plecanatide and its active metabolite bind to GC-C receptors on the surface of intestinal cells. This activation raises levels of a signaling molecule called cyclic GMP both inside and outside the cells, a change linked to increased fluid secretion into the intestine.

What Plecanatide Is Approved For

Trulance is approved for adults with chronic idiopathic constipation and for adults with irritable bowel syndrome with constipation (IBS-C). These are two of the most common functional gastrointestinal disorders that lead patients to seek prescription treatment. The label for this medication carries a boxed warning, meaning prescribers and patients should be aware of a serious risk noted prominently on the packaging.

What the Evidence Shows

Plecanatide has been studied in at least 15 registered clinical trials. Among the sample of studies, a Phase 3 trial evaluated plecanatide specifically for IBS-C and has been completed, as has a separate Phase 3 long-term safety study. An earlier Phase 2 trial also examined plecanatide for IBS-C and reached completed status, contributing early evidence before the drug advanced to larger studies.

Reported Side Effects

Postmarket safety reports for plecanatide are dominated by gastrointestinal complaints. Diarrhoea is by far the most reported reaction, followed by nausea, constipation, and abdominal distension. Other frequently reported terms include abdominal pain, upper abdominal pain, fatigue, and reports of the drug being ineffective. These figures reflect the number of reports submitted to a safety surveillance system, not confirmed rates of occurrence or proof that the drug caused each event.