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.
RM-131 accelerated gastric emptyingRelamorelin significantly sped up stomach emptying and reduced symptom scores in diabetic gastroparesis patients in clinical trials
What the researchers 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.
Why it 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.
How the study worked
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.
What this study cannot 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.
How to read the evidence
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.
When this study was published
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.
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.
Questions still open
- 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?
Common questions
What is gastroparesis and why is it hard to treat?
How does ghrelin help the stomach empty?
Read the original research
Therapeutic applications of ghrelin agonists in the treatment of gastroparesis.
Current gastroenterology reports, 17(2), 430
Citation
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