Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis.
BACKGROUND
TZP-101 is a synthetic, selective ghrelin agonist in development for gastroparesis.


OBJECTIVE
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.
Ejskjaer
N
N
Aarhus University Hospital, Aarhus, Denmark.
Vestergaard
E T
ET
Hellström
P M
PM
Gormsen
L C
LC
Madsbad
S
S
Madsen
J L
JL
Jensen
T A
TA
Pezzullo
J C
JC
Christiansen
J S
JS
Shaughnessy
L
L
Kosutic
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D018592:Cross-Over Studies; D048909:Diabetes Complications / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D018589:Gastroparesis / Q000188:drug therapy* / Q000209:etiology; D054439:Ghrelin / Q000819:agonists* / Q000627:therapeutic use; D015309:Glucose Clamp Technique; D006801:Humans; D047028:Macrocyclic Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D001786:Blood Glucose; D054439:Ghrelin; D047028:Macrocyclic Compounds; C528884:ulimorelin