Ulimorelin
A ghrelin agonist that moved the stomach but not the colon
Ulimorelin is an investigational macrocyclic drug that activates the ghrelin receptor, which stimulates gut movement. Developed to shorten the gut shutdown that follows bowel surgery, it looked promising in a phase 2 trial, but two phase 3 trials found no benefit. A later study showed why: it speeds stomach emptying but has no measurable effect on the colon.
What is it?
Ghrelin, the hunger hormone, also stimulates the gut. Ulimorelin came from a screening programme of macrocyclic compounds against the human ghrelin receptor, optimised for potency and pharmacokinetics. It was developed for postoperative ileus, the temporary paralysis of the bowel after abdominal surgery that keeps patients in hospital.
In phase 2, the most effective dose (480 µg/kg) shortened time to gastrointestinal recovery after colectomy, an effect that remained significant after adjusting for surgery type and opioid use (hazard ratio 1.81). But in two phase 3 trials, of 332 and 330 patients, neither dose differed from placebo on the primary endpoint or on time to first bowel movement, tolerating solid food or discharge eligibility. Serious adverse events were similar across groups.
A 2020 human study offered an explanation. Ulimorelin sped liquid gastric emptying by 23% to 46%, but had no effect on colonic transit, and the authors suggested the free drug levels and dosing frequency in the ileus trials may have been too low. In rats, it drives colorectal propulsion through the lumbosacral spinal cord, and in rodents and humans it lowers blood pressure and dilates vessels through actions independent of the ghrelin receptor.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Published Research
Studies of ulimorelin, from their PubMed abstracts.
Two phase 3 trials in postoperative ileus
In studies 007 (332 patients) and 008 (330), neither dose of ulimorelin differed from placebo on the primary endpoint or on time to first bowel movement, tolerance of solid food or discharge eligibility; serious adverse events were comparable.
Phase 2 after colectomy
At 480 µg/kg, the most effective dose, ulimorelin shortened time to gastrointestinal recovery after adjustment for surgery type and opioid use (hazard ratio 1.81, P = 0.014).
Stomach yes, colon no
Doses of 150-600 µg/kg every 8 hours sped liquid gastric emptying by 23% to 46% through day 6 but did not change colonic transit; the authors suggested drug levels in the ileus trials may have been inadequate.
How it drives defecation in rats
Intravenous ulimorelin caused about an hour of increased colorectal propulsion, prevented by cutting lumbosacral nerves, by hexamethonium or by ghrelin receptor antagonists, and mimicked by applying it to the lumbosacral spinal cord.
Effects on blood vessels
Ulimorelin, which lowers blood pressure in rodents and humans, dilated rodent arteries through mechanisms independent of the ghrelin receptor.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
No label; it is investigational.
Legal Status
Ulimorelin is investigational.
Frequently Asked Questions
?What was ulimorelin for?
Shortening postoperative ileus, the temporary shutdown of the bowel after abdominal surgery, by activating the ghrelin receptor.
?Why did it fail?
Two phase 3 trials found no benefit over placebo. A later study showed it speeds stomach emptying but not colonic transit, and the authors suggested the doses in the ileus trials may have been too low.
?Is ulimorelin a peptide?
It is a macrocyclic peptidomimetic: a ring-shaped molecule designed to act on the ghrelin receptor rather than a natural peptide.
?Does it affect blood pressure?
Yes: it lowers blood pressure in rodents and humans, and rodent studies show it dilates arteries through mechanisms that do not depend on the ghrelin receptor.
References
- [clinical-trial] Shaw M, et al. "Safety and efficacy of ulimorelin administered postoperatively to accelerate recovery of gastrointestinal motility following partial bowel resection: results of two randomized, placebo-controlled phase 3 trials." Dis Colon Rectum, 2013;56(7):888-97. PMID: 23739196.
- [clinical-trial] Bochicchio G, et al. "Ghrelin agonist TZP-101/ulimorelin accelerates gastrointestinal recovery independently of opioid use and surgery type: covariate analysis of phase 2 data." World J Surg, 2012;36(1):39-45. PMID: 22072430.
- [clinical-trial] James J, et al. "The effects of ulimorelin, a ghrelin agonist, on liquid gastric emptying and colonic transit in humans." Neurogastroenterol Motil, 2020;32(3):e13784. PMID: 32017341.
- [pubmed] Pustovit RV, et al. "The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin." Neurogastroenterol Motil, 2014;26(2):264-71. PMID: 24304447.
- [pubmed] Broad J, et al. "Analysis of the ghrelin receptor-independent vascular actions of ulimorelin." Eur J Pharmacol, 2015;752:34-9. PMID: 25687251.
Sources & Citations
Studies were read from their PubMed records, October 3, 2026.
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