title: The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus.
abstract: OBJECTIVE
  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 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.
authors: Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota.
authors: Andrea
authors: A
authors: Shin
authors: Michael
authors: M
authors: Camilleri
authors: Irene
authors: I
authors: Busciglio
authors: Duane
authors: D
authors: Burton
authors: Steven A
authors: SA
authors: Smith
authors: Adrian
authors: A
authors: Vella
authors: Michael
authors: M
authors: Ryks
authors: Deborah
authors: D
authors: Rhoten
authors: Alan R
authors: AR
authors: Zinsmeister
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000502:physiology; D018589:Gastroparesis / Q000188:drug therapy*; D054439:Ghrelin / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D054439:Ghrelin
keywords: AE; CF6; CRU; Clinical Research Unit; Clinical Trial; DGE; Drug; GCSI-DD; GE; GI; Gastroparesis; IQR; NVFP; Prokinetic; T1DM; T2DM; adverse event; colonic filling at 6 hours; daily diary of gastroparesis cardinal symptom index; delayed gastric emptying; gastric emptying; gastrointestinal; interquartile range; nausea, vomiting fullness, pain; t(1/2); the calculated time point at which 50% of the radiolabeled meal has emptied from the stomach; type 1 diabetes mellitus; type 2 diabetes mellitus
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