Relamorelin: Physiology and What Research Reports

What relamorelin is

Relamorelin (also written in the literature as RM-131) is a synthetic pentapeptide analogue of ghrelin that acts as an agonist at the growth hormone secretagogue receptor type 1a (GHS-R1a), the receptor through which endogenous ghrelin signals. A 2015 review in Neurogastroenterology and Motility described relamorelin as a novel gastrocolokinetic synthetic ghrelin agonist developed for neurogastroenterology indications, meaning researchers were interested in effects on both stomach and colon motility (PMID 25545036). A later review of the compound in Expert Opinion on Investigational Drugs framed relamorelin as an investigational agent for gastrointestinal motility disorders, administered by subcutaneous injection in the trial programme (PMID 28847163).

An important distinction: relamorelin is not produced in the human body. It is a laboratory-designed analogue. What is produced in the body is ghrelin, the hormone whose receptor relamorelin engages — and that endogenous system is what gives the peptide its physiological rationale.

The ghrelin pathway: where it comes from and what it does

Ghrelin is a stomach-derived peptide hormone released largely from specialised endocrine cells of the gastric mucosa. Reviews of ghrelin receptor agonists have summarised its physiological roles as including stimulation of growth hormone secretion, appetite signalling, and promotion of gastric and colonic motility, which is why agonists were investigated for gastroparesis, functional dyspepsia and proton pump inhibitor–resistant non-erosive reflux disease (PMID 29550791). A companion review in the Journal of Neurogastroenterology and Motility discussed the same receptor family in the context of constipation-associated disorders, where the motility-stimulating arm of ghrelin signalling is the property of interest (PMID 28238253).

In short: the physiology being borrowed is a gut-to-brain and gut-to-muscle signalling loop that normally helps coordinate hunger and the movement of contents through the digestive tract. Relamorelin was built to engage that loop selectively and with a longer duration of action than native ghrelin, which is rapidly degraded.

How relamorelin has been studied

Because the target physiology is motility, the research methods are largely functional measurements rather than blood levels of the peptide itself. Across the published programme, researchers used approaches such as:

• Gastric emptying measurement of solids and liquids, used as the primary physiological readout in gastroparesis work (PMID 27055601).
• Colonic transit measurement in chronic constipation, where the study assessed whether transit accelerated relative to placebo (PMID 26001337).
• Direct colonic motility recording, used in a randomised controlled trial of short-term effects on descending colon motility in chronic constipation (PMID 26467700).
• Gastric motor function and satiation testing in healthy volunteers, where researchers examined gastric functions and satiation together rather than symptoms alone (PMID 27283792).
• Patient-reported symptom diaries, including vomiting frequency and composite gastroparesis symptom scores, used as clinical endpoints in the diabetic gastroparesis trials (PMID 28760384).

What the literature reports

Diabetic gastroparesis

A 2016 phase 2 report in Gastroenterology stated in its title and findings that relamorelin reduced vomiting frequency and severity and accelerated gastric emptying in adults with diabetic gastroparesis (PMID 27055601). A subsequent randomised, placebo-controlled study in diabetics with symptoms of gastroparesis evaluated multiple twice-daily subcutaneous dose levels of relamorelin against placebo over a 12-week treatment period and reported effects on gastroparesis symptoms and gastric emptying (PMID 28760384). A 2023 meta-analysis pooled gastroparesis and diabetic gastroparesis data and reported on both efficacy signals and safety across the included trials (PMID 38058346).

Chronic constipation

A phase 2, placebo-controlled randomised trial reported that relamorelin relieved constipation and accelerated colonic transit (PMID 26001337). A separate randomised controlled trial examined short-term effects on descending colon motility in chronic constipation, providing a mechanistic counterpart to the transit and symptom findings (PMID 26467700).

Constipation in Parkinson's disease

The MOVE-PD randomised trial tested relamorelin for constipation in Parkinson's disease, and researchers published the trial results together with an explicit discussion of methodological lessons learned for designing future constipation trials in this population (PMID 28237854).

Healthy volunteers

In healthy participants, the study of the ghrelin receptor agonist examined gastric motor functions and satiation, addressing whether motility effects seen in patients also appeared in non-diseased physiology (PMID 27283792).

Relamorelin Adverse Events: What Studies Report

A pooled analysis in Alimentary Pharmacology & Therapeutics examined the overall safety of relamorelin in adults with diabetic gastroparesis using phase 2a and 2b trial data, and researchers focused particularly on glycaemic measures in participants with diabetes alongside general tolerability (PMID 32301137). The 2023 meta-analysis also addressed safety as a formal outcome domain across gastroparesis and diabetic gastroparesis trials rather than efficacy alone (PMID 38058346). Review articles covering the compound likewise discussed tolerability alongside the motility findings when weighing the place of ghrelin receptor agonists in gastrointestinal disease (PMID 28847163). Readers who encounter relamorelin in a clinical context should note that adverse-event profiles reported in supervised trials cannot be generalised to other settings. This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about symptoms, medications or investigational compounds.

Why the term matters to readers

Relamorelin appears in peptide discussions for three reasons. First, it is one of the clearest examples of a peptide designed to exploit a single receptor pathway — GHS-R1a — for a specific organ function rather than a broad hormonal effect. Second, its development programme is unusually well documented in peer-reviewed journals, including phase 2 trials, mechanistic motility studies, a pooled safety analysis and a meta-analysis, which makes it a useful case study in how peptide claims are tested (PMID 38058346). Third, it is frequently confused with growth-hormone-directed ghrelin mimetics; the reviews positioned relamorelin specifically within motility disorders such as gastroparesis, functional dyspepsia and reflux research rather than as a growth-hormone agent (PMID 29550791).

Limitations of the current evidence

The published work is dominated by phase 2 trials with relatively short treatment periods, and the MOVE-PD experience illustrated how placebo response and endpoint selection can complicate constipation research in a neurological population (PMID 28237854). Reviews of constipation-associated disorders noted that the broader class of ghrelin receptor agonists remained under investigation rather than established practice (PMID 28238253). Relamorelin has been described throughout this literature as an investigational compound; nothing on this page describes an approved therapy or a protocol.

References

• Relamorelin in Gastroparesis and Diabetic Gastroparesis: A Meta-Analysis on Its Efficacy and Safety (Cureus, 2023)
• Relamorelin and other ghrelin receptor agonists - future options for gastroparesis, functional dyspepsia and proton pump inhibitors-resistant non-erosive reflux disease (Journal of Physiology and Pharmacology, 2017)
• Emerging treatments in Neurogastroenterology: relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist (Neurogastroenterology and Motility, 2015)
• Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults With Diabetic Gastroparesis (Gastroenterology, 2016)
• Relamorelin for the treatment of gastrointestinal motility disorders (Expert Opinion on Investigational Drugs, 2017)
• Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists (Journal of Neurogastroenterology and Motility, 2017)
• Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study (Gastroenterology, 2017)
• Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial (Clinical Gastroenterology and Hepatology, 2015)
• Short-Term Effects of Relamorelin on Descending Colon Motility in Chronic Constipation: A Randomized, Controlled Trial (Digestive Diseases and Sciences, 2016)
• Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data (Alimentary Pharmacology & Therapeutics, 2020)
• A randomized trial of relamorelin for constipation in Parkinson's disease (MOVE-PD): Trial results and lessons learned (Parkinsonism & Related Disorders, 2017)
• Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers (Neurogastroenterology and Motility, 2016)