Is plecanatide FDA-approved, and what does the research show?

What is plecanatide?

Plecanatide is a man-made peptide, a short chain of 16 amino acids, the building blocks of proteins ¹. The label calls it "a structural analog of human uroguanylin" ¹. Uroguanylin is a peptide the body makes itself ².

Its drug class is the guanylate cyclase-C agonists ¹. GC-C, short for guanylate cyclase-C, is a switch on the gut's lining cells, and an agonist is a drug that turns a switch on ¹. Salix Pharmaceuticals, a division of Bausch Health, sells it in the United States as Trulance, a tablet taken by mouth ¹. Linaclotide, sold as Linzess, is a different molecule in the same class and has its own page on this site.

Plecanatide is a prescription medicine for constipation, not a wellness, weight or performance peptide. The label's two uses are bowel disorders, and it names nothing for weight, muscle, aging or performance ¹.

Is plecanatide FDA-approved?

Yes. Plecanatide is approved by FDA as the prescription medicine Trulance, with initial U.S. approval in 2017 ¹. FDA's Drugs@FDA record, its public register of approved drugs, shows new drug application NDA 208745, approved January 19, 2017, with marketing status "Prescription" ³. The approval letter went to Synergy Pharmaceuticals, "for the treatment of chronic idiopathic constipation (CIC) in adults" ⁴. A supplement approved January 24, 2018 added "a new indication for irritable bowel syndrome with constipation (IBS-C)" ⁵.

Drugs@FDA lists no generic application for plecanatide as of November 9, 2026, the date of its data ³. The record now names Salix Pharmaceuticals as the sponsor ³. The current label, revised in March 2024, says Trulance "is indicated in adults for the treatment of: chronic idiopathic constipation (CIC)" and "irritable bowel syndrome with constipation (IBS-C)" ¹, ⁹.

The Medication Guide explains the first condition: "Idiopathic means the cause of the constipation is unknown" ¹. In the label's trials, chronic idiopathic constipation meant fewer than three bowel movements a week for at least three months ¹. It came with at least two of straining, hard or lumpy stools, a sense of incomplete emptying or of blockage ¹.

Irritable bowel syndrome is recurrent abdominal pain or discomfort tied to a change in bowel habit ¹. The IBS-C form is the one in which at least a quarter of stools are hard or lumpy ¹. Only a licensed clinician's prescription leads to it ³, ¹.

See the FDA status of every peptide, updated weekly.

How does plecanatide work?

Plecanatide "functions as a guanylate cyclase-C (GC-C) agonist," the label says, in the same way as uroguanylin ¹. Plecanatide, together with the active fragment the gut cuts it into, binds GC-C ¹. The label says both "act locally on the luminal surface of the intestinal epithelium," the gut's inner lining ¹. Once GC-C is activated, a messenger molecule called cyclic GMP builds up both within the lining cells and outside them ¹. The build-up within the cells drives secretion of chloride and bicarbonate into the bowel, "resulting in increased intestinal fluid and accelerated transit" ¹.

In animal models, the label adds, the rise in cyclic GMP outside the cells "has been associated with a decrease in the activity of pain-sensing nerves" ¹. In one such model, plecanatide reduced abdominal muscle contractions, a measure of intestinal pain ¹.

Very little of the drug reaches the bloodstream ¹. The label describes it as "minimally absorbed with negligible systemic availability," and in most plasma samples neither it nor its active form could be measured ¹. It is broken down in the gut into smaller peptides and amino acids ¹.

What does the research show?

FDA approved plecanatide on four randomized, double-blind, placebo-controlled trials in adults, so its evidence level is "Approved for a use" ¹, ³. In a double-blind trial, neither the patients nor their doctors know who is on the drug until it ends. In a placebo-controlled trial, one group takes a look-alike tablet with no drug in it, so any gap between the groups is the drug's doing. Each was a phase 3 trial, the large final stage before approval, and randomized patients to the approved dose, a higher dose or placebo for 12 weeks ⁶, ⁷, ². The label recommends only the approved dose, because the higher one "did not demonstrate additional treatment benefit" and, in the chronic idiopathic constipation trials, "had a greater incidence of adverse reactions" ¹.

Studied in people with chronic idiopathic constipation: a phase 3 trial published online in February 2017 randomized 1,394 adults ⁶. A CSBM, a complete spontaneous bowel movement, is the label's term for a bowel movement with no laxative behind it and "a sense of complete evacuation" ¹. The label defines the primary endpoint as "at least 3 CSBMs in a given week and an increase of at least 1 CSBM from baseline in the same week for at least 9 weeks out of the 12-week treatment period and at least 3 of the last 4 weeks" ¹. On the approved dose, 21.0 percent met it, against 10.2 percent on placebo ⁶.

The label's Study 1, with 453 patients on the approved dose against 452 on placebo, matches this trial's two arms ¹. The treatment difference was 11 percentage points, with a 95 percent confidence interval, the range the true difference most likely falls in, of 6.1 to 15.4 ¹.

A second phase 3 trial of the same design, published online in October 2017, randomized 1,410 adults ². Of them, 443 on the approved dose, 449 on the higher one and 445 on placebo were analyzed ². The responder rate was 20.1 percent on the approved dose against 12.8 percent on placebo ². The label's Study 2, close to it in size (430 and 440 patients) and result, gives the difference as 8 percentage points, with a confidence interval of 2.6 to 12.4 ¹.

In the second trial, the authors wrote, the gain in bowel movements began in week 1 and held through week 12 ². By the label's account, patients "generally returned to baseline" in the two weeks after treatment stopped ¹.

Studied in people with irritable bowel syndrome with constipation: two identical phase 3 trials, published together online in March 2018, randomized 2,189 adults between them ⁷. A responder met two criteria in the same week "for at least 6 of the 12 treatment weeks" ¹. The label's pain criterion is "a decrease in the weekly average of worst abdominal pain" of "at least 30%," and its stool criterion "an increase of at least 1 CSBM per week from baseline" ¹. In the first trial, 30.2 percent on the approved dose met the endpoint against 17.8 percent on placebo; in the second, 21.5 percent against 14.2 ⁷. The label reports them as Studies 3 and 4, with differences of 12 points (confidence interval 6 to 18) and 7 points (2 to 13) ¹.

Studied in a third population: a phase 3 trial at 40 hospitals in China, published online in June 2025, randomized 648 adults with functional constipation ⁸. They took the approved dose or placebo for 12 weeks ⁸. On the drug, 23.5 percent met the trial's durable response endpoint, a sustained rise in complete spontaneous bowel movements, against 10.2 percent on placebo ⁸. Plasma levels of plecanatide and its metabolite stayed below the limit of quantification at every time point ⁸. The trial's diagnosis was functional constipation, a term the U.S. label does not use ⁸, ¹.

Two open-label extension studies, in which every patient knew they were taking the drug, followed tolerability for longer. In chronic idiopathic constipation, 2,370 patients took it for up to 72 weeks, most on the higher dose ¹⁰. In IBS-C, 2,272 patients took the higher dose for up to 53 weeks, and 81.1 percent completed ¹¹. Both studies measured safety and tolerability, not efficacy against placebo ¹⁰, ¹¹. Synergy Pharmaceuticals, which developed the drug, funded both studies ¹⁰, ¹¹.

No published trial of plecanatide for weight, muscle, performance, aging or any condition other than constipation was found as of November 10, 2026 ⁶, ⁷, ², ⁸. None ran a blinded comparison beyond 12 weeks ⁶, ⁷, ², ⁸. FDA's approval letter required studies in children aged 2 to 17 ⁴. The 2024 label still says safety and effectiveness "have not been established in patients less than 18 years of age" ¹.

What are the side effects?

Diarrhea is the main side effect, and the label gives its rate in both patient groups. In the two pooled constipation trials, 863 patients took the approved dose and 870 took placebo ¹. Diarrhea was reported by 5 percent against 1 percent, the only adverse reaction at or above 2 percent ¹. Most cases began within four weeks, and severe diarrhea occurred in 0.6 percent against 0.3, within the first three days ¹. In all, 4 percent on the drug and 2 percent on placebo stopped for adverse reactions, and 2 percent against 0.5 stopped for diarrhea ¹.

Less common reactions in those trials were sinusitis, upper respiratory infection, abdominal distension, flatulence and abdominal tenderness ¹. Two patients on the drug had the liver enzyme ALT rise to between 5 and 15 times the upper limit of normal ¹. Three had AST, another liver enzyme, above 5 times ¹.

In the two pooled IBS-C trials, 723 patients took the drug and 726 took placebo ¹. Diarrhea was reported by 4.3 percent against 1 percent, and severe diarrhea by 1 percent against 0.1, within the first day ¹. Discontinuations for adverse reactions were 2.5 percent against 0.4, and 1.2 percent stopped for diarrhea against none on placebo ¹. Nausea, nasopharyngitis (the common cold), upper respiratory infection, urinary tract infection and dizziness were each reported by 1 to 2 percent, more than on placebo ¹.

In the long-term open-label studies, diarrhea was reported by 7.1 percent over up to 72 weeks in chronic constipation and 6.7 percent over up to 53 weeks in IBS-C ¹⁰, ¹¹. It led 3.1 and 2.7 percent to stop ¹⁰, ¹¹. Since approval, the label says, reports have included "hypersensitivity reactions: skin itching, hives, rash" and vomiting ¹. Should diarrhea turn severe, the label directs prescribers to "suspend dosing and rehydrate the patient" ¹.

At the head of the label sits a boxed warning, "WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS" ¹. It reads: "TRULANCE is contraindicated in patients less than 6 years of age; in nonclinical studies in young juvenile mice, administration of a single oral dose of plecanatide caused deaths due to dehydration" ¹. It adds: "Avoid use of TRULANCE in patients 6 years to less than 18 years of age" ¹. The mice that died were at an age the label equates to human infants of about one month to under two years ¹. Children under 6, it explains, have more GC-C in the gut and so "may be more likely" to develop severe diarrhea and its consequences ¹.

The label names two contraindications, the cases in which it must not be given ¹. They are children under 6 and "known or suspected mechanical gastrointestinal obstruction," meaning a bowel blocked by something physical ¹. Accidental swallowing by a child, "especially in children less than 6 years of age, may result in severe diarrhea and dehydration," the label warns ¹. It asks patients to keep the tablets where children cannot reach them ¹.

In pregnancy, the label expects no exposure of the fetus, because the drug is "negligibly absorbed" ¹. It calls the human pregnancy data "not sufficient to inform any drug-associated risks for major birth defects and miscarriage" ¹. It was not measurable in breast milk after two weeks of use ¹. In two-year animal studies it did not cause tumors in mice or rats ¹.

In sport

WADA, the World Anti-Doping Agency, does not name plecanatide or Trulance in its 2026 Prohibited List ¹². Its sections for peptide hormones (S2) and hormone and metabolic modulators (S4) list neither the drug nor its class ¹².

What JumpstartMD offers

JumpstartMD does not prescribe plecanatide. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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Compounded medications are not FDA-approved, and FDA does not review their safety, effectiveness, or quality before they are marketed. A licensed clinician decides after an evaluation whether a peptide is appropriate for you, and not every patient will qualify.