Dexloxiglumide for the treatment of constipation predominant irritable bowel syndrome

ABSTRACT

Introduction: Irritable bowel syndrome (IBS) is a multifactorial functional gut disorder, where sensory/motor disturbances seem to play a major role, with no satisfactory treatment for a majority of patients. Cholecystokinin (CCK) is a hormone with several effects on gastrointestinal function, and IBS patients have been shown to produce altered sensory/motor responses to CCK.

Areas covered: Dexloxiglumide is a selective antagonist of the type 1 receptor of CCK, which has demonstrated to revert the CCK mediated effects on gastrointestinal motility and sensitivity. In humans, Dexloxiglumide has been shown to accelerate gastric emptying, slow down transit in the proximal colon, and increase the tolerance to intestinal gas. In phase 2 clinical trials Dexloxiglumide 200 mg tid has demonstrated to be superior to placebo in symptom relief in constipation predominant IBS (IBS-C). In a phase 3 withdrawal study Dexloxiglumide obtained a more sustained effect than placebo. However, these promising effects in IBS-C have not been confirmed in large phase 3 studies so far.

Expert opinion: Dexloxiglumide has demonstrated positive effects on important aspects of gastrointestinal function, like gastric emptying and gas tolerance, that deserves consideration in future studies. However, the available data is insufficient to recommend dexloxiglumide for treatment of IBS-C today.

KEYWORDS:

• Irritable bowel syndrome
• constipation
• dexloxiglumide
• cholecystokinin

Declaration of interest

J Serra is contracted as medical advisor and has got reimbursement for lectures by Norgine and Reckitt Benckiser. J Serra has participated in advisory boards organized by Almirall, Allergan and Shionogi, and has delivered reimbursed lectures in symposia promoted by Zespri. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The study was co-financed by a Grant from the Spanish Ministry of Health (Fondo de Investigaciones Sanitarias PI14/01703) and European Funds for Regional Development (FEDER). Dr Caballero had a Grant from The Catalan Society of Gastroenterology (Beca d’iniciació a la recerca).