Relamorelin
GI Motility / RecoveryAlso known as: RM-131, Allergan Relamorelin
Mechanism
Relamorelin is a synthetic ghrelin analog developed for diabetic gastroparesis. It activates the ghrelin receptor to speed up stomach emptying and reduce nausea and vomiting in patients whose diabetes has damaged their stomach nerves. Phase 2 trials showed meaningful improvements in gastric emptying time and symptoms.
Technical detail
Relamorelin (RM-131) is a synthetic pentapeptide ghrelin analog and selective GHS-R1a agonist. It accelerates gastric emptying by activating ghrelin receptors on gastric smooth muscle and vagal afferent neurons, enhancing antral contractility and antropyloroduodenal coordination. Subcutaneous administration demonstrated significantly accelerated gastric emptying and symptom improvement in Phase 2 trials in diabetic gastroparesis patients. Growth hormone release occurs but is not the primary therapeutic target.
Evidence
- moderate
Relamorelin in Gastroparesis and Diabetic Gastroparesis: A Meta-Analysis on Its Efficacy and Safety
(2023) — Springer Science and Business Media LLC — PMID: 10.7759/cureus.48303
Relamorelin significantly improves gastric emptying time in gastroparesis and diabetic gastroparesis patients. The mean difference in gastric emptying time was -11.40 minutes compared to the placebo group, with a -8.43 minutes difference specifically in diabetic gastroparesis patients. Adverse effects include headaches, dizziness, and gastrointestinal symptoms.
- moderate
Camilleri et al. (2020) — Alimentary Pharmacology & Therapeutics — PMID: 32301137
Pooled safety analysis of 204 phase 2a and 393 phase 2b diabetic gastroparesis participants found similar serious adverse event rates across groups, but relamorelin arms had more treatment-emergent discontinuations and post hoc analyses supported monitoring for worsening glycemic control.
- moderate
Michael Camilleri et al. (2020) — Aliment Pharmacol Ther — PMID: 10.1111/apt.15711
Across phase 2 diabetic gastroparesis trials, relamorelin showed acceptable tolerability and similar serious adverse-event rates to placebo, but produced dose-related rises in HbA1c and fasting glucose that warrant proactive monitoring.
- moderate
Relamorelin for the treatment of gastrointestinal motility disorders.
Chedid V, Camilleri M (2017) — Expert opinion on investigational drugs — PMID: 28847163
Narrative review summarizes human relamorelin data showing accelerated gastric emptying, symptom improvement in diabetic gastroparesis and chronic idiopathic constipation studies, and a generally favorable neurologic and cardiovascular safety profile in trials to date.
- strong
Camilleri et al. (2017) — Gastroenterology — PMID: 28760384
In 393 adults with diabetic gastroparesis, relamorelin significantly reduced composite symptom scores over 12 weeks and accelerated gastric emptying versus placebo; vomiting frequency fell about 75% from baseline but was not significantly different from placebo, and dose-related worsening of glycemic control occurred in some patients.
- moderate
(2017) — Elsevier BV — PMID: 10.1053/j.gastro.2017.07.035
Relamorelin significantly reduced symptoms of diabetic gastroparesis and accelerated gastric emptying compared to placebo; 75% reduction in vomiting frequency but not significant vs placebo; dose-related worsening of glycemic control noted
- emerging
(2017) — Elsevier BV — PMID: 10.1016/j.parkreldis.2017.02.003
The study investigated relamorelin for constipation in Parkinson's disease patients. Due to recruitment challenges and a high rate of partially complete bowel movements, the trial did not demonstrate a beneficial effect of relamorelin. However, it provided insights into the complex nature of constipation in PD patients.
- emerging
Parkinson Study Group (2017) — Parkinsonism & related disorders — PMID: 28237854
Randomized placebo-controlled Parkinson disease constipation study was underpowered because recruitment and eligibility assumptions failed, so efficacy could not be demonstrated, but it highlighted that constipation in PD is more complex than stool frequency alone.
- strong
(2016) — Elsevier BV — PMID: 10.1053/j.gastro.2016.03.038
Relamorelin, administered subcutaneously at a dose of 10 μg twice daily, significantly accelerated gastric emptying and reduced vomiting frequency and severity by approximately 60% in patients with diabetic gastroparesis, with notable improvements in patients with baseline vomiting.
- strong
Lembo et al. (2016) — Gastroenterology — PMID: 27055601
In 204 adults with diabetic gastroparesis, relamorelin 10 micrograms twice daily significantly accelerated gastric emptying and reduced vomiting frequency and severity versus placebo; among participants with baseline vomiting it also improved nausea, pain, bloating, and early satiety without major overall safety concerns.
- strong
Acosta A, Camilleri M, Kolar G, Iturrino J, Szarka LA, Boldingh A, Burton D, Ryks M, Rhoten D, Zinsmeister AR, Spence SC, Gottesdiener K, Bouras EP, Vazquez-Roque MI. (2015) — Clin Gastroenterol Hepatol — PMID: 26001337
Phase 2 placebo-controlled randomized trial in chronic constipation found relamorelin accelerated gastric emptying and colonic transit and improved bowel movement endpoints over 14 days.
- strong
Acosta A, Camilleri M, Kolar G, Iturrino J, Szarka LA, Boldingh A (2015) — Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association — PMID: 26001337
Phase 2 placebo-controlled randomized trial in chronic constipation found subcutaneous relamorelin improved bowel function endpoints and accelerated colonic transit, supporting prokinetic activity beyond gastric emptying.
- moderate
(2015) — Springer Science and Business Media LLC — PMID: 10.1007/s10620-015-3876-5
Relamorelin, 100 μg, significantly induced more pre-meal and post-meal propagated contractions compared to placebo in patients with chronic constipation.