Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial

Introduction-Erythromycin, a motilin agonist, is a potent prokinetic. ABT-2 29 is a specific motilin agonist that dose dependently accelerates gastric emptying. Dyspepsia and gastroparesis are common problems in type I diabete s mellitus. We aimed to evaluate the efficacy of ABT-229 in symptomatic dia betic patients with and without delayed gastric emptying. Methods-Patients with type 1 diabetes and postprandial symptoms were random ised (n=270). Based on a validated C-13 octanoic acid breath test, patients were assigned to either the delayed or normal gastric emptying strata. Pat ients received one of four doses of ABT-229 (1.25, 2.5, 5, or 10 mg twice d aily before breakfast and dinner) or placebo for four weeks following a two week baseline. A self report questionnaire measured symptoms on visual ana logue scales; the primary outcome was assessment of change in the total upp er abdominal symptom severity score (range 0-800 mm) from baseline to the f inal visit. Results-The treatment arms were similar regarding baseline characteristics. There was symptom improvement on placebo and a similar level of improvemen t on active therapy for the upper abdominal discomfort severity score (mean change from baseline -169, -101, -155, -143, and -138 mm for placebo, and 1.25, 2.5, 5, and 10 mg ABT-229, respectively, at four weeks by intent to t reat). The results were not significantly different in those with and witho ut delayed gastric emptying. The severity of bloating, postprandial nausea, epigastric discomfort, heartburn, and acid regurgitation worsened dose dep endently in a greater number of patients receiving ABT-229 than placebo. Ov erall, 63% of patients on placebo reported a good or excellent global respo nse, and this was not different from the active treatment arms. Conclusions-The motilin agonist ABT-229 was not efficacious in the relief o f postprandial symptoms in diabetes mellitus in the presence or absence of delayed gastric emptying.