Ghrelin Agonists for Gastroparesis: RM-131 Accelerated Stomach Emptying Where Earlier Drugs Failed

The ghrelin receptor agonist RM-131 (relamorelin) significantly accelerated gastric emptying in diabetic gastroparesis patients, while an earlier oral ghrelin agonist (TZP-102) failed to replicate promising IV results.

Shin, Andrea et al.·Current gastroenterology reports·2015·
RPEP-027922015RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Not classified
Evidence
Not graded
Sample
Not reported

What This Study Found

The ghrelin receptor agonist RM-131 significantly accelerated gastric emptying in patients with type 1 and type 2 diabetes and delayed gastric emptying. RM-131 also reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) scores among type 1 diabetic patients. Earlier intravenous administration of TZP-101 showed symptom improvement, but oral TZP-102 did not confirm these effects.

Key Numbers

How They Did This

The study reviewed clinical trials involving ghrelin receptor agonists in diabetic gastroparesis patients, comparing intravenous and oral administration effects on gastric emptying and symptom scores.

Why This Research Matters

Gastroparesis currently lacks effective treatments, so ghrelin agonists offer a potential new therapy to improve patient quality of life by enhancing stomach motility and reducing symptoms.

The Bigger Picture

Gastroparesis treatment options are extremely limited — metoclopramide (with serious neurological side effects) is essentially the only FDA-approved drug. Ghrelin agonists represent a mechanistically different approach by leveraging the body's natural prokinetic peptide system. RM-131 (relamorelin) continued in development after this review was published, though it ultimately didn't achieve FDA approval. The concept of using ghrelin-pathway drugs for GI motility remains active, especially relevant now as GLP-1 drugs (which slow gastric emptying) are creating more gastroparesis cases.

What This Study Doesn't Tell Us

The evidence strength and study types are not clearly defined, and some ghrelin agonists showed inconsistent results depending on administration route. Further large-scale, controlled trials are needed.

Questions This Raises

  • ?Could ghrelin agonists treat the GLP-1 drug-induced gastroparesis that's becoming more common with widespread semaglutide use?
  • ?Why did TZP-101 work intravenously but TZP-102 failed orally — is oral bioavailability the key barrier?
  • ?Would combining ghrelin agonists with other prokinetics produce synergistic effects on gastric emptying?

Trust & Context

Key Stat:
RM-131 accelerated gastric emptying Relamorelin significantly sped up stomach emptying and reduced symptom scores in diabetic gastroparesis patients in clinical trials
Evidence Grade:
This is a clinical review summarizing results from multiple clinical trials of ghrelin agonists. The reviewed evidence includes controlled human trials, but the overall picture is mixed — one drug succeeded (RM-131), one failed (TZP-102), limiting definitive conclusions about the drug class.
Study Age:
Published in 2015, this review captures an early stage of ghrelin agonist clinical development for gastroparesis. RM-131 (relamorelin) continued in clinical trials but ultimately did not achieve FDA approval. The unmet need in gastroparesis treatment remains substantial.
Original Title:
Therapeutic applications of ghrelin agonists in the treatment of gastroparesis.
Published In:
Current gastroenterology reports, 17(2), 430 (2015)
Database ID:
RPEP-02792

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

What is gastroparesis and why is it hard to treat?

Gastroparesis means the stomach empties food too slowly, causing nausea, vomiting, bloating, and malnutrition. It's particularly common in diabetes because nerve damage affects stomach muscle function. Treatment options are very limited — metoclopramide (the only approved drug) has serious neurological side effects, and many patients don't respond to it.

How does ghrelin help the stomach empty?

Ghrelin is a natural hormone that stimulates stomach contractions and speeds food through the digestive system — that's why you feel your stomach churning when you're hungry. Ghrelin receptor agonists mimic this effect pharmacologically, making the stomach contract more effectively. RM-131 (relamorelin) showed this works in clinical trials, significantly accelerating gastric emptying in diabetic patients.

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Cite This Study

RPEP-02792·https://rethinkpeptides.com/research/RPEP-02792

APA

Shin, Andrea; Wo, John M. (2015). Therapeutic applications of ghrelin agonists in the treatment of gastroparesis.. Current gastroenterology reports, 17(2), 430. https://doi.org/10.1007/s11894-015-0430-8

MLA

Shin, Andrea, et al. "Therapeutic applications of ghrelin agonists in the treatment of gastroparesis.." Current gastroenterology reports, 2015. https://doi.org/10.1007/s11894-015-0430-8

RethinkPeptides

RethinkPeptides Research Database. "Therapeutic applications of ghrelin agonists in the treatmen..." RPEP-02792. Retrieved from https://rethinkpeptides.com/research/shin-2015-therapeutic-applications-of-ghrelin

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Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.