Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

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Abstract

There remains an unmet need for effective pharmacologic treatments for gastroparesis. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and has been shown to regulate energy homeostasis and exert prokinetic effects on gastrointestinal motility. In recent years, several ghrelin receptor agonists have been studied in clinical trials of patients with diabetic gastroparesis. The intravenous macrocyclic peptidomimetic, TZP-101, initially suggested improvement in gastroparesis symptoms with intravenous administration when compared to placebo. However, in subsequent studies of oral preparations, TZP-102 failed to confirm these results. Another ghrelin receptor agonist, RM-131, was recently shown to significantly accelerate gastric emptying (GE) in patients with type 1 and type 2 diabetes and delayed GE. RM-131 reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) and composite scores among type 1 diabetics. Continued development of ghrelin agonists should be explored in attempts to expand therapeutic options for the treatment of gastroparesis.

Original languageEnglish
JournalCurrent Gastroenterology Reports
Volume17
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Gastroparesis
Ghrelin
Ghrelin Receptor
Gastric Emptying
Peptidomimetics
Therapeutics
Gastrointestinal Motility
Type 1 Diabetes Mellitus
Intravenous Administration
Type 2 Diabetes Mellitus
Homeostasis
Placebos
Clinical Trials
Ligands

Keywords

  • Diabetes
  • Gastric emptying
  • Gastroparesis
  • Ghrelin
  • Growth hormone
  • Motilin
  • Orexigenic hormone
  • RM-131
  • TZP 102
  • TZP-101
  • Ulimorelin
  • Vagus

ASJC Scopus subject areas

  • Gastroenterology

Cite this

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title = "Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis",
abstract = "There remains an unmet need for effective pharmacologic treatments for gastroparesis. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and has been shown to regulate energy homeostasis and exert prokinetic effects on gastrointestinal motility. In recent years, several ghrelin receptor agonists have been studied in clinical trials of patients with diabetic gastroparesis. The intravenous macrocyclic peptidomimetic, TZP-101, initially suggested improvement in gastroparesis symptoms with intravenous administration when compared to placebo. However, in subsequent studies of oral preparations, TZP-102 failed to confirm these results. Another ghrelin receptor agonist, RM-131, was recently shown to significantly accelerate gastric emptying (GE) in patients with type 1 and type 2 diabetes and delayed GE. RM-131 reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) and composite scores among type 1 diabetics. Continued development of ghrelin agonists should be explored in attempts to expand therapeutic options for the treatment of gastroparesis.",
keywords = "Diabetes, Gastric emptying, Gastroparesis, Ghrelin, Growth hormone, Motilin, Orexigenic hormone, RM-131, TZP 102, TZP-101, Ulimorelin, Vagus",
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AB - There remains an unmet need for effective pharmacologic treatments for gastroparesis. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and has been shown to regulate energy homeostasis and exert prokinetic effects on gastrointestinal motility. In recent years, several ghrelin receptor agonists have been studied in clinical trials of patients with diabetic gastroparesis. The intravenous macrocyclic peptidomimetic, TZP-101, initially suggested improvement in gastroparesis symptoms with intravenous administration when compared to placebo. However, in subsequent studies of oral preparations, TZP-102 failed to confirm these results. Another ghrelin receptor agonist, RM-131, was recently shown to significantly accelerate gastric emptying (GE) in patients with type 1 and type 2 diabetes and delayed GE. RM-131 reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) and composite scores among type 1 diabetics. Continued development of ghrelin agonists should be explored in attempts to expand therapeutic options for the treatment of gastroparesis.

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