Ulimorelin

Mechanism

Ulimorelin is a ghrelin receptor agonist developed to treat gastroparesis — a condition where the stomach empties too slowly. By activating the same receptor as the hunger hormone ghrelin, it stimulates stomach contractions and accelerates gastric emptying. It reached Phase 3 trials for postoperative ileus but did not gain approval.

Evidence

• A multicenter, randomized, double-blind study of ulimorelin and metoclopramide in the treatment of critically ill patients with enteral feeding intolerance: PROMOTE trial

  Heyland et al. (2019) — Intensive Care Medicine — PMID: 31062046

  In 120 ICU patients with enteral feeding intolerance, ulimorelin and metoclopramide achieved similar feeding success and safety outcomes over 5 days, without a clear efficacy advantage for ulimorelin.

  moderate

• 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

  Shaw et al. (2013) — Diseases of the Colon and Rectum — PMID: 23739196

  Across two placebo-controlled phase 3 trials in post-colectomy patients, intravenous ulimorelin was generally well tolerated but did not significantly reduce postoperative ileus endpoints versus placebo.

  moderate

• The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus.

  Shin A et al. (2013) — Clin Gastroenterol Hepatol — PMID: 23639598

  Double-blind crossover trial in 10 adults with type 1 diabetes and delayed gastric emptying found a single 100 microgram subcutaneous RM-131 dose shortened solid gastric emptying half-time from 118.7 to 84.9 minutes and improved gastroparesis symptom scores without significant adverse effects.

  strong

• Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting--randomised clinical study subset data.

  Wo JM, Ejskjaer N, Hellström PM, Malik RA, Pezzullo JC, Shaughnessy L, Charlton P, Kosutic G, McCallum RW. (2011) — Aliment Pharmacol Ther — PMID: 21214610

  TZP-101 (ulimorelin) significantly improved nausea and vomiting symptoms in diabetic gastroparesis patients at a dose of 80 μg/kg, reducing GCSI Nausea/Vomiting subscale scores by -3.82±0.76 (P=0.011) and total GCSI scores by -3.14±0.78 (P=0.016).

  moderate

• Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study.

  Ejskjaer N, Dimcevski G, Wo J, Hellström PM, Gormsen LC, Gormsen LC, Sarosiek I, Søfteland E, Nowak T, Pezzullo JC, Shaughnessy L, Kosutic G, McCallum R. (2010) — Neurogastroenterol Motil — PMID: 20524987

  TZP-101 (a ghrelin agonist) showed efficacy in relieving symptoms of diabetic gastroparesis at a dose of 80 μg/kg, with significant improvements in Loss of Appetite, Vomiting, and Postprandial fullness scores.

  moderate

• Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis.

  Ejskjaer N, Vestergaard ET, Hellström PM, Gormsen LC, Gormsen LC, Madsbad S, Madsen JL, Jensen TA, Pezzullo JC, Christiansen JS, Shaughnessy L, Kosutic G. (2009) — Aliment Pharmacol Ther — PMID: 19298585

  TZP-101, a ghrelin receptor agonist, significantly accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis at doses of 80, 160, 320, or 600 mcg/kg. The study found a 20% reduction in solid meal half-emptying time and a 34% reduction in latency time compared to placebo.

  moderate