A ghrelin agonist fails to show benefit in patients with diabetic gastroparesis: Let's not throw the baby out with the bath water

摘要

Ghrelin is the endogenous ligand for the growth hormone secretagogue-1a receptor and is a potential target for treatment of gastroparesis. This viewpoint assesses the potential role of ghrelin agonists in the treatment of gastroparesis through a review of the early phase, randomized, controlled trials of ghrelin agonists in patients with diabetes and, either, delayed gastric emptying at the time of the trial or symptoms at the time of the trial, and prior documentation of delayed gastric emptying of solids. Whereas recent experience with ghrelin agonists that have a macrocycle structure (TZP-101, TZP-102) has not confirmed earlier promising results, there is little evidence that ghrelin receptors downregulate with repeated treatment, in contrast to motilin receptors. Phase IIa clinical trials performed with a different agent (RM-131, which is a small molecule ghrelin agonist) suggest that, as a class, ghrelin agonists may be efficacious in stimulating gastric emptying. It is premature to dismiss ghrelin agonists as potential therapies for gastroparesis.