{"id":"linaclotide","name":"Linaclotide","aliases":["Linzess","Constella","MD-1100"],"url":"https://lyoresearch.com/compounds/linaclotide","class":{"id":"gut-peptides","name":"Gut and intestinal peptides","url":"https://lyoresearch.com/classes/gut-peptides"},"summary":"Linaclotide is a 14-amino-acid peptide with three disulfide bonds, approved since 2012 as Linzess and Constella for irritable bowel syndrome with constipation and for chronic idiopathic constipation. It is taken as a capsule and is minimally absorbed — it acts on guanylate cyclase-C receptors on the luminal surface of the intestine. In a 26-week phase 3 trial, 33.7% of treated patients met the FDA responder endpoint against 13.9% on placebo. Diarrhoea is the dose-limiting effect.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Phase 3 programme (n=804 in the trial quoted here)","regulatory_status":"Approved (Rx)","molecule":{"formula":"C59H79N15O21S6","molecular_weight":"1526.8","cas":"851199-59-2","pubchem_cid":16158208,"sequence":"CCEYCCNPACTGCY","sequence_note":"Three disulfide bridges.","note":null},"pharmacokinetics":{"basis":"label","route":"Oral capsule, once daily","half_life":"Cannot be calculated: the label describes linaclotide as minimally absorbed with negligible systemic availability","licensed_regimen":"One capsule once daily on an empty stomach, at a strength set by the indication","product":"Linzess","source":{"title":"Linzess prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09beda19-56d6-4a56-afdc-9a77b70b2ef3"}},"outcomes":[{"outcome":"Irritable bowel syndrome with constipation","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT (n=804, 26 wk)","evidence":"A 26-week randomised placebo-controlled trial in 804 patients with IBS-C: a third met the composite FDA responder endpoint for abdominal pain and bowel movements, against a seventh on placebo — a number needed to treat of about five.","references":[{"citation":"Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety.","where":"Am J Gastroenterol, 2012;107:1702–1712","url":"https://pubmed.ncbi.nlm.nih.gov/22986437/"}],"verbatim":{"text":"In all, 804 patients (mean age = 44 years, female = 90 % , white = 78 % ) were evaluated; 33.7 % of linaclotide-treated patients were FDA end point responders, vs. 13.9 % of placebo-treated patients ( P < 0.0001) (number needed to treat = 5.1, 95 % confidence interval (CI): 3.9, 7.1).","citation":"Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety.","url":"https://pubmed.ncbi.nlm.nih.gov/22986437/"}},{"outcome":"Chronic idiopathic constipation","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Approval programme","evidence":"A separate licensed indication with its own phase 3 trials at lower doses; the label carries both, and a paediatric functional-constipation indication was added later.","references":[{"citation":"Linzess (linaclotide) prescribing information.","where":"DailyMed, read 29 Oct 2026","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09beda19-56d6-4a56-afdc-9a77b70b2ef3"}]},{"outcome":"Diarrhoea","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"1 phase 3 RCT (n=804); approval programme","evidence":"The mechanism's own side effect and the reason people stop. Otherwise the adverse-event profile matched placebo. The label carries a contraindication in patients under 2 years of age on the basis of deaths in juvenile animal studies.","references":[{"citation":"Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety.","where":"Am J Gastroenterol, 2012;107:1702–1712","url":"https://pubmed.ncbi.nlm.nih.gov/22986437/"},{"citation":"Linzess (linaclotide) prescribing information.","where":"DailyMed, read 29 Oct 2026","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09beda19-56d6-4a56-afdc-9a77b70b2ef3"}],"verbatim":{"text":"AE incidence was similar between treatment groups, except for diarrhea, which caused discontinuation in 4.5 % of linaclotide patients vs. 0.2 % of placebo patients.","citation":"Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety.","url":"https://pubmed.ncbi.nlm.nih.gov/22986437/"}},{"outcome":"Systemic effects","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"Label pharmacokinetics","evidence":"The Linzess label describes the drug as minimally absorbed with negligible systemic availability, so no half-life can be calculated. A peptide drug with essentially no systemic exposure — the reason its safety profile is a gastrointestinal one.","references":[{"citation":"Linzess (linaclotide) prescribing information.","where":"DailyMed, read 29 Oct 2026","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09beda19-56d6-4a56-afdc-9a77b70b2ef3"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Constella authorised centrally in 2012 for moderate to severe IBS with constipation in adults."},{"region":"United States","status":"Approved, prescription-only","note":"Linzess approved in 2012 for IBS-C and chronic idiopathic constipation in adults, with a paediatric functional-constipation indication added in 2023. Contraindicated under 2 years of age."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Constella licensed by the MHRA."},{"region":"Australia","status":"Registered, Schedule 4","note":"Constella registered on the ARTG."},{"region":"Canada","status":"Authorised, prescription-only","note":"Constella authorised with a Drug Identification Number."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not named on the Prohibited List."}],"faq":[{"q":"How can a peptide be taken as a capsule?","a":"Because it does not have to be absorbed. Linaclotide's three disulfide bonds hold it together through the stomach, and its target sits on the luminal surface of the intestine. The label describes negligible systemic availability — no blood levels to speak of, so no half-life to quote."},{"q":"How well does linaclotide work for IBS-C?","a":"About a third of patients met the composite responder endpoint in a 26-week trial against a seventh on placebo — roughly one additional responder for every five treated."},{"q":"Why does it cause diarrhoea?","a":"Because that is the mechanism at a higher intensity. The receptor it activates is the one bacterial toxins use to cause secretory diarrhoea; about one in twenty patients stops the drug because of it."}],"references":[{"cite":"Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety.","where":"Am J Gastroenterol, 2012;107:1702–1712","url":"https://pubmed.ncbi.nlm.nih.gov/22986437/","note":"804 patients evaluated; 26 weeks; 290 µg once daily."},{"cite":"Linzess (linaclotide) prescribing information.","where":"DailyMed, read 29 Oct 2026","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09beda19-56d6-4a56-afdc-9a77b70b2ef3","note":"Oral route, negligible systemic availability, indications and the contraindication under 2 years of age."},{"cite":"PubChem compound record: linaclotide.","where":"PubChem, read 29 Oct 2026","url":"https://pubchem.ncbi.nlm.nih.gov/compound/16158208","note":"Formula, molecular weight, CAS and the 14-residue sequence used on this page."}],"last_reviewed":"2026-10-29","literature_searched_to":"2026-10-29","changelog":[{"date":"2026-10-29","note":"Initial publication. Grade A on the phase 3 programme."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}