Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis
Article first published online: 27 FEB 2009
© 2009 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 29, Issue 11, pages 1179–1187, June 2009
How to Cite
EJSKJAER, N., VESTERGAARD, E. T., HELLSTRÖM, P. M., GORMSEN, L. C., MADSBAD, S., MADSEN, J. L., JENSEN, T. A., PEZZULLO, J. C., CHRISTIANSEN, J. S., SHAUGHNESSY, L. and KOSUTIC, G. (2009), Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Alimentary Pharmacology & Therapeutics, 29: 1179–1187. doi: 10.1111/j.1365-2036.2009.03986.x
- Issue published online: 21 MAY 2009
- Article first published online: 27 FEB 2009
- Publication data Submitted 22 December 2008 First decision 14 January 2009 Resubmitted 19 January 2009 Accepted 24 February 2009 Epub Accepted Article 24 February 2009
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 μg/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 ≥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.