The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus
A Shin, M Camilleri, I Busciglio, D Burton… - Clinical …, 2013 - Elsevier
A Shin, M Camilleri, I Busciglio, D Burton, SA Smith, A Vella, M Ryks, D Rhoten…
Clinical Gastroenterology and Hepatology, 2013•ElsevierBackground & Aims RM-131, a synthetic ghrelin agonist, greatly accelerates gastric
emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We
investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper
gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented
DGE. Methods In a double-blind cross-over study, 10 patients with type 1 diabetes (age,
45.7±4.4 y; body mass index, 24.1±1.1 kg/m 2) and previously documented DGE were …
emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We
investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper
gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented
DGE. Methods In a double-blind cross-over study, 10 patients with type 1 diabetes (age,
45.7±4.4 y; body mass index, 24.1±1.1 kg/m 2) and previously documented DGE were …
Background & Aims
RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE.
Methods
In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m2) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid–liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0−5 scale).
Results
At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, –49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects.
Conclusions
RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE. ClinicalTrials.gov: NCT01394055.
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