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Peptide

Plecanatide (Trulance)

Plecanatide is a 16-amino acid synthetic uroguanylin analog and guanylate cyclase-C agonist. FDA-approved 2017 for CIC, 2018 for IBS-C. Phase 3: 21% durable CSBM responders vs 10.2% placebo in CIC (P<0.001). 30% overall responders vs 17.8% placebo in IBS-C. Lower diarrhea rate (5%) than linaclotide. Dose: 3 mg once daily.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
2
Outcomes
8
Graded outcomes
4112

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

2 conditions, plus general outcomes

Constipation

Constipation: outcomes studied for Plecanatide (Trulance)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Abdominal Bloating

Significant improvement in bloating, cramping, discomfort, and fullness vs placebo. Benefits observed by week 1 and sustained through 12 weeks. Similar efficacy to linaclotide with lower diarrhea rate.

Improves (the measure goes down)Large effect12 studies

Studies that measured abdominal bloating

and 2 more in the citations list

Durable CSBM Response CIC

Phase 3: 21.0% durable overall CSBM responders (3mg) vs 10.2% placebo (P<0.001). Responders had ≥3 CSBMs/week with ≥1 increase for ≥9 of 12 weeks. CSBM frequency increased 2.5/week vs 1.2/week placebo.

Improves (the measure goes up)Large effect11 studies

Studies that measured durable csbm response cic

and 1 more in the citations list

Constipation-Predominant Irritable Bowel Syndrome (IBS-C)

Constipation-Predominant Irritable Bowel Syndrome (IBS-C): outcomes studied for Plecanatide (Trulance)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Overall Response IBS-C

Phase 3: 30.2% overall responders (3mg) vs 17.8% placebo (P<0.001). Dual endpoint: ≥30% pain reduction + ≥1 CSBM increase for ≥6 of 12 weeks. Consistent across two identical trials (n=2,189).

Improves (the measure goes up)Large effect8 studies

Studies that measured overall response ibs-c

Abdominal Pain IBS-C

Significant reduction in worst abdominal pain vs placebo. ≥30% improvement in pain required for FDA responder endpoint. cGMP-mediated visceral analgesia mechanism.

Improves (the measure goes down)Large effect8 studies

Studies that measured abdominal pain ibs-c

General

General: outcomes studied for Plecanatide (Trulance)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Safety/Tolerability

13 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Moderate effect12 studies

Studies that measured safety/tolerability

and 2 more in the citations list

GI Protection

4 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect6 studies

Studies that measured gi protection

Anti-Inflammatory Activity

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies

Studies that measured anti-inflammatory activity

Anti-Cancer Activity

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies

Studies that measured anti-cancer activity

Key findings

  • Abdominal BloatingConstipationImproves (the measure goes down)
  • Durable CSBM Response CICConstipationImproves (the measure goes up)
  • Overall Response IBS-CConstipation-Predominant Irritable Bowel Syndrome (IBS-C)Improves (the measure goes up)

Studies cited

28 studies from PubMed

  1. Efficacy and tolerability of plecanatide for irritable bowel syndrome with constipation and chronic idiopathic constipation: a systematic review and meta-analysis.European journal of gastroenterology & hepatology, 2026 · PMID 41604554
  2. Post-marketing safety assessment of constipation drugs: a real-world pharmacovigilance study based on FAERS database.Expert opinion on drug safety, 2025 · PMID 39950440
  3. The Safety of Pharmacotherapy for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.The American journal of gastroenterology, 2025 · PMID 40471839
  4. Constipation-predominant irritable bowel syndrome treatment options Linaclotide, Lubiprostone, Plecanatide, and Tenapanor: analysis of the FDA Adverse Event Reporting System (FAERS) database.Expert opinion on drug safety, 2025 · PMID 40503810
  5. Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.Drugs, 2025 · PMID 40571893
  6. Plecanatide Is Efficacious in Women Aged 18 to 40 Years With IBS-C and Bloating: A Pooled Analysis of Two Phase 3, Randomized, Placebo-Controlled Trials.Gastroenterology & hepatology, 2025 · PMID 41625190
  7. Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with ConstipationAm J Gastroenterol, 2024 · PMID 38691604
  8. Assessing real-world safety of plecanatide: a pharmacovigilance study based on the FDA adverse event reporting system.Frontiers in pharmacology, 2024 · PMID 39654622
  9. Efficacy and Safety of Plecanatide in Treatment of Irritable Bowel Syndrome With Constipation and Chronic Idiopathic Constipation.Gastroenterology & hepatology, 2024 · PMID 39896924
  10. Plecanatide Improves Symptoms of Irritable Bowel Syndrome with Constipation: Results of an Integrated Efficacy and Safety Analysis of Two Phase 3 TrialsDig Dis Sci, 2023 · PMID 37507497
  11. Plecanatide Improves Symptoms of Irritable Bowel Syndrome with Constipation: Results of an Integrated Efficacy and Safety Analysis of Two Phase 3 Trials.International journal of general medicine, 2023 · PMID 37649852
  12. The Effect of Acid Suppression Therapy on the Safety and Efficacy of Plecanatide: Analysis of Randomized Phase III TrialsJ Clin Gastroenterol, 2022 · PMID 35086735
  13. Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer.Personalized medicine, 2022 · PMID 35920071
  14. Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential.Expert opinion on therapeutic targets, 2021 · PMID 34056991
  15. Evaluation of Plecanatide for the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation in Patients 65 Years or OlderClin Transl Gastroenterol, 2020 · PMID 32660770
  16. Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trialsAm J Gastroenterol, 2018 · PMID 29545635
  17. Plecanatide: a new guanylate cyclase agonist for the treatment of chronic idiopathic constipationTherap Adv Gastroenterol, 2018 · PMID 29782529
  18. Plecanatide (Trulance) for Chronic Idiopathic Constipation and Irritable Bowel Syndrome With ConstipationMed Lett Drugs Ther, 2018 · PMID 29521975
  19. Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders.Gut, 2018 · PMID 29563144
  20. Safety and tolerability of plecanatide in patients with chronic idiopathic constipation: long-term evidence from an open-label study.Current medical research and opinion, 2018 · PMID 29343131
  21. Efficacy and safety of plecanatide in treating constipation predominant irritable bowel syndrome.Expert opinion on pharmacotherapy, 2018 · PMID 29376436
  22. Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis.Gastroenterology, 2018 · PMID 30144426
  23. A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic ConstipationAm J Gastroenterol, 2017 · PMID 28169285
  24. Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipationTherap Adv Gastroenterol, 2017 · PMID 29147135
  25. Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc(+/Min-FCCC) mice.World journal of gastrointestinal pharmacology and therapeutics, 2017 · PMID 28217374
  26. Formulary Drug Reviews: Plecanatide.Hospital pharmacy, 2017 · PMID 29276262
  27. Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis.World journal of gastrointestinal pharmacology and therapeutics, 2015 · PMID 26558155
  28. Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well-tolerated in single doses.Digestive diseases and sciences, 2013 · PMID 23625291