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

doi:10.1136/gut.49.3.395

Gut 2001;49:395-401; doi:10.1136/gut.49.3.395

Gut 2001;49:395-401 ( September )

Article

Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial N J Talley^a, M Verlinden^b, D J Geenen^c, R B Hogan^d, D Riff^e, R W McCallum^f, R J Mack^b

^a Department of Medicine, University of Sydney, Nepean Hospital, Penrith NSW, Australia, ^b Abbott Laboratories, Abbott Park Illinois, USA, ^c Gastroenterology Consultants Ltd, Milwaukee, Wisconsin, USA, ^d Mississippi Center for Clinical Research, Jackson, Mississippi, USA, ^e Associated Gastroenterology Group, Anaheim, California, USA, ^f University of Kansas Medical Center, Kansas City, Kansas, USA

Correspondence to: Professor N J Talley, Department of Medicine, University of Sydney, Nepean Hospital, PO Box 63, Penrith NSW 2751, Australia.

Accepted for publication 5 December 2000

INTRODUCTION $---$ Erythromycin, a motilin agonist, is a potent prokinetic. ABT-229 is a specific motilin agonist that dose dependently acceleratesgastric emptying. Dyspepsia and gastroparesis are common problemsin type 1 diabetes mellitus. We aimed to evaluate the efficacyof ABT-229 in symptomatic diabetic patients with and without delayedgastricemptying.
METHODS $---$ Patients with type 1 diabetes and postprandial symptoms were randomised (n=270). Based on a validated C¹³ octanoic acid breath test, patients were assigned to either thedelayed or normal gastric emptying strata. Patients received oneof four doses of ABT-229 (1.25, 2.5, 5, or 10 mg twice daily beforebreakfast and dinner) or placebo for four weeks following a twoweek baseline. A self report questionnaire measured symptoms onvisual analogue scales; the primary outcome was assessment ofchange in the total upper abdominal symptom severity score (range0-800 mm) from baseline to the finalvisit.
RESULTS $---$ The treatment arms were similar regarding baseline characteristics. There was symptom improvement on placebo and a similarlevel of improvement on active therapy for the upper abdominaldiscomfort severity score (mean change from baseline $-$ 169, $-$ 101, $-$ 155, $-$ 143, and $-$ 138 mm for placebo, and 1.25, 2.5, 5, and 10mg ABT-229, respectively, at four weeks by intent to treat). Theresults were not significantly different in those with and withoutdelayed gastric emptying. The severity of bloating, postprandialnausea, epigastric discomfort, heartburn, and acid regurgitationworsened dose dependently in a greater number of patients receivingABT-229 than placebo. Overall, 63% of patients on placebo reporteda good or excellent global response, and this was not differentfrom the active treatmentarms.
CONCLUSIONS $---$ The motilin agonist ABT-229 was not efficacious in the relief of postprandial symptoms in diabetes mellitus in the presenceor absence of delayed gastricemptying.

Keywords: prokinetic; motilin; dyspepsia; gastric motility; type 1 diabetes; controlled trial; postprandial

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