The Ghrelin Agonist RM-131 Accelerates Gastric Emptying of Solids and Reduces Symptoms in Patients With Type 1 Diabetes Mellitus

• Published in: Clinical gastroenterology and hepatology Vol. 11; no. 11; pp. 1453 - 1459.e4
• Main Authors: Shin, Andrea, Camilleri, Michael, Busciglio, Irene, Burton, Duane, Smith, Steven A., Vella, Adrian, Ryks, Michael, Rhoten, Deborah, Zinsmeister, Alan R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Adult; Aged; Animals; Clinical Trial; Cross-Over Studies; Diabetes Mellitus, Type 1 - complications; Double-Blind Method; Drug; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Gastric Emptying - drug effects; Gastroenterology and Hepatology; Gastrointestinal Agents - administration & dosage; Gastrointestinal Agents - adverse effects; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - physiology; Gastroparesis; Gastroparesis - drug therapy; Ghrelin - agonists; Humans; Male; Middle Aged; Prokinetic; Radionuclide Imaging; Treatment Outcome; Young Adult; Drug; T1DM; T2DM; GI; DGE; Clinical Trial; AE; CRU; IQR; CF6; t1/2; NVFP; Prokinetic; GCSI-DD; Gastroparesis; GE; daily diary of gastroparesis cardinal symptom index; delayed gastric emptying; colonic filling at 6 hours; interquartile range; gastric emptying; type 2 diabetes mellitus; t 1/2; type 1 diabetes mellitus; Clinical Research Unit; nausea, vomiting fullness, pain; adverse event; gastrointestinal; the calculated time point at which 50% of the radiolabeled meal has emptied from the stomach; t(1/2)
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2013.04.019

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. 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). 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. 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.