Metoclopramide in the treatment of diabetic gastroparesis

Abstract

Gastroparesis is a chronic disorder that affects a significant subset of the population. Diabetes mellitus is a risk factor for the development of gastroparesis. Currently, metoclopramide is the only US FDA-approved medication for the treatment of gastroparesis. However, the FDA recently placed a black-box warning on metoclopramide because of the risk of related side effects, including tardive dyskinesia, the incidence of which has been cited to be as high as 15% in the literature. This review will investigate the mechanisms by which metoclopramide improves the symptoms of gastroparesis and will focus on the evidence of clinical efficacy supporting metoclopramide use in gastroparesis. Finally, we seek to document the true complication risk from metoclopramide, especially tardive dyskinesia, by reviewing the available evidence in the literature. Potential strategies to mitigate the risk of complications from metoclopramide will also be discussed.

Figures

Figure 1. Metoclopramide

Metoclopramide is a substituted benzamide derivative.

Figure 2. Mechanism of action of metoclopramide

(A) Metoclopramide promotes gut motility by inhibiting presynaptic and postsynaptic D2 receptors as well as presynaptic 5-HT4 receptors. (B) Metoclopramide also produces antiemetic effects by inhibition of D2 and 5-HT3 receptors in the CTZ. CTZ: Chemoreceptor trigger zone; GI: Gastrointestinal. Adapted from [30].