Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis.

Abstract

BACKGROUND:

TZP-101 is a synthetic, selective ghrelin agonist in development for gastroparesis.

AIM:

To assess safety and effects of TZP-101 in diabetes patients with symptomatic gastroparesis.

METHODS:

Adults with type 1 or type 2 diabetes mellitus received placebo and TZP-101 (80, 160, 320 or 600 microg/kg) infusions in a cross-over manner following a radiolabelled meal. Blood glucose levels were stabilized using a hyperinsulinemic-euglycemic clamp. Primary endpoints were gastric half emptying and latency times. Secondary measures included assessment of gastroparesis symptoms and endocrine responses.

RESULTS:

Ten patients with type 1 (n = 7) or 2 (n = 3) diabetes, moderate-to-severe gastroparesis symptoms and > or =29% retention 4 h after a radiolabelled solid meal were enrolled. TZP-101 produced significant reductions in solid meal half-emptying (20%, P = 0.043) and latency (34%, P = 0.037) times vs. placebo. Reductions in overall postmeal symptom intensity (24%) and postprandial fullness (37%) following TZP-101 infusion were not statistically significant. Most adverse events were mild and self-limiting and there were no identifiable differences in numbers or types of adverse events between TZP-101 and placebo.

CONCLUSIONS:

This proof-of-concept study demonstrates that the ghrelin agonist TZP-101 is well-tolerated in diabetes patients with moderate-to-severe chronic gastroparesis and shows statistically significant improvements in gastric emptying.

• Authors: N Ejskjaer, E T Vestergaard, P M Hellström, L C Gormsen, S Madsbad, J L Madsen, T A Jensen, J C Pezzullo, J S Christiansen, L Shaughnessy, G Kosutic
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 29 Issue 11 Pg. 1179-87 (Jun 01 2009) ISSN: 1365-2036 [Electronic] England
• PMID: 19298585 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Ghrelin
• Macrocyclic Compounds
• ulimorelin

Topics

• Adolescent
• Adult
• Aged
• Blood Glucose
• Cross-Over Studies
• Diabetes Complications (complications, drug therapy)
• Double-Blind Method
• Female
• Gastric Emptying (drug effects)
• Gastroparesis (drug therapy, etiology)
• Ghrelin (agonists, therapeutic use)
• Glucose Clamp Technique
• Humans
• Macrocyclic Compounds (therapeutic use)
• Male
• Middle Aged
• Treatment Outcome
• Young Adult