Linaclotide and plecanatide are closely related FDA-approved gut drugs — both are guanylate cyclase-C (GC-C) agonists that act locally in the intestine to increase fluid secretion and ease constipation. They're used for chronic idiopathic constipation and IBS-C. Plecanatide is the newer agent, designed to mimic the body's natural uroguanylin.
At a glance
| Linaclotide | Plecanatide | |
|---|---|---|
| Class | Guanylate cyclase-C agonist | Guanylate cyclase-C agonist |
| Brand name | Linzess | Trulance |
| FDA status | Approved | Approved |
| Used for | Chronic constipation, IBS-C | Chronic constipation, IBS-C |
| Action site | Local in the gut | Local in the gut |
| Design note | Heat-stable enterotoxin–based | Mimics natural uroguanylin (pH-sensitive) |
The bottom line
Bottom line: Very similar drugs with the same mechanism and indications. Both are approved, gut-local GC-C agonists for constipation and IBS-C. Plecanatide is designed to resemble the body's own uroguanylin and act in a pH-dependent way, which is sometimes associated with a different tolerability profile. The choice is clinical.
Frequently asked questions
What's the difference between linaclotide and plecanatide?
Both are FDA-approved guanylate cyclase-C agonists that act locally in the gut for constipation and IBS-C. Plecanatide is newer and designed to mimic the body's natural uroguanylin in a pH-dependent way; otherwise their mechanism is very similar.
Are Linzess and Trulance the same?
They are the same class of drug (GC-C agonists) for similar uses, but Linzess is linaclotide and Trulance is plecanatide — different molecules. Both are FDA-approved and act locally in the intestine.
Do these peptides get absorbed into the body?
They are designed to act locally in the gut with minimal systemic absorption, which is part of why they can be taken orally — unlike most peptides, they don't need to reach the bloodstream.
References
Combined peer-reviewed sources from both peptide guides. Inclusion is not endorsement.
- Rao S, Lembo AJ, Shiff SJ, et al. A 12-week randomized controlled trial of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012. Peer-reviewed study
- Lembo AJ, Schneier HA, Shiff SJ, et al. Two Randomized Trials of Linaclotide for Chronic Constipation. N Engl J Med. 2011. Peer-reviewed study
- Di Lorenzo C, Khlevner J, Rodriguez-Araujo G, et al. Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Gastroenterol Hepatol. 2024. Peer-reviewed study
- Rao SS, Manabe N, Karasawa Y, et al. Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm. BMC Gastroenterol. 2024. Peer-reviewed study
- Kalola UK, Patel P, Chowdhury YS. Linaclotide. 2026. Peer-reviewed study
- Taclob JA, Kalas MA, McCallum RW. Examining linaclotide for the treatment of chronic idiopathic constipation. Expert Opin Pharmacother. 2024. Peer-reviewed study
- Al-Salama ZT, Syed YY. Plecanatide: First Global Approval. Drugs. 2017. Peer-reviewed study
- Love BL. Plecanatide for Treatment of Chronic Constipation and Irritable Bowel Syndrome. Am J Med. 2019. Peer-reviewed study
- Bassotti G, Usai Satta P, Bellini M. Plecanatide for the treatment of chronic idiopathic constipation in adult patients. Expert Rev Clin Pharmacol. 2019. Peer-reviewed study
- Rao SSC. Plecanatide: a new guanylate cyclase agonist for the treatment of chronic idiopathic constipation. Ther Adv Gastroenterol. 2018. Peer-reviewed study
- Miner PB. Plecanatide for the treatment of constipation-predominant irritable bowel syndrome. Expert Rev Gastroenterol Hepatol. 2020. Peer-reviewed study
- Bai T, Xu Z, Zhen Y, et al. Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Drugs. 2025. Peer-reviewed study