Metoclopramide for the treatment of diabetic gastroparesis

ABSTRACT

Introduction: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of gastroparesis. Management of diabetic gastroparesis involves lifestyle modifications, glycemic control, pharmacological drugs, and for refractory cases surgical treatments. Metoclopramide remains the only drug approved by the Food and Drug Administration for diabetic gastroparesis. The aim of this article is to provide a concise review of the pharmacology, clinical efficacy and tolerability of metoclopramide.

Areas covered: We searched PubMed using the key words ‘metoclopramide’, ‘diabetic gastroparesis’, and ‘gastric emptying’. The relevant articles and their bibliography were reviewed. Metoclopramide acts on several different receptors; primarily as a dopamine receptor antagonist, both peripherally improving gastric emptying, and centrally resulting in an anti-emetic effect. Metoclopramide side effects, mostly related to its ability to cross the blood-brain barrier, include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible.

Expert opinion: Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD. However, gastroparesis patients experience chronic symptoms often requiring prolonged treatments. Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profile.

KEYWORDS:

• Metoclopramide
• gastroparesis
• diabetic gastroparesis
• gastric emptying
• tardive dyskinesia

Article highlights

• Metoclopramide, available in the USA since 1979, acts on several receptors including the D2 receptors and 5HT4 receptors.

• Metoclopramide is the only FDA approved medication for diabetic gastroparesis treatment. FDA recommends limiting its use to less than 12 weeks, in comparison to the EMA which recommends using it for 5 days only and does not recommend using it for gastroparesis.

• Start metoclopramide use with the lower dose if possible, such as 5 mg po qac and titrate as tolerated. The maximum dose is 40 mg daily (divided as 10 mg QID).

• Most of the side effects of metoclopramide including akathisia, parkinsonism, and tardive dyskinesia are related to its central action. Any development of a movement disorder should prompt a physician to stop the medication

• Patients’ medication list review is important before prescribing metoclopramide as movement side effect is higher and more severe with patients on anti-psychotic medications.

• Newer pharmacological agents with better efficacy and safer side effect profile are needed to improve management of gastroparesis.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.