Metoclopramide in the Treatment of Diabetic Gastroparesis

Allen Lee; Braden Kuo

Expert Rev Endocrinol Metab. 2010;5(5):653-662.

Chemistry

Metoclopramide (4-amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide) is a substituted benzamide derivative (Figure 1) with a chemical structure similar to procainamide but without anti-arrhythmic effects.

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Figure 1.

Metoclopramide. Metoclopramide is a substituted benzamide derivative.

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Cite this: Metoclopramide in the Treatment of Diabetic Gastroparesis - Medscape - Sep 01, 2010.

Table 1. Risk of tardive dyskinesia with metoclopramide.
Study (year)	Study design	Number studied	Result	Estimated prevalence	Ref.
Wilholm et al. (1984)	Scandinavian prescription database, 1977–1981	11 million Rx of metoclopramide	37 reports of EPS with 11 TD casesAll females, mean age of 76 years	One in 2000–28,000 patient-years, one in 17,800 perscriptions	^[71]
Bateman et al. (1985)	UK prescription database, 1967–1982	15.9 million Rx of metoclopramide	479 reports of EPS, four with TD	One in ~35,000 prescriptions, significantly higher risk in females, especially those 12–19 years old	^[64]
Sewell et al.(1992)	Analysis of 67 case reports of metaclopramide-induced TD	52 patients on at least 30 days of metoclopramide	Mean age of 70 ± 19 years, 3:1 female predominance and Rx duration of 20 ± 15 months; 47% TD cases persisted at 6 months despite discontinuation of metoclopramide	Not estimable	^[74]
Ganzini et al. (1993)	VA study using exposed/unexposed design, matched for age, gender, diabetes and comorbidities	51 chronic Rx of metoclopramide; 51 unexposed	Mean age of 63.9 ± 10.8 years, male predominant, duration of treatment 2.6 ± 2.0 years	29% TD in metoclopramide Rx vs 17.6% in nonusers (p = 0.08)	^[65]
Sewell et al. (1994)	VA cross-sectional study	51 patients with metoclopramide-associated TD; 35 controls matched for age, race, gender and diabetes	Duration of metoclopramide treatment of at least 30 days	27% TD in metoclopramide Rx vs 12% nonusers (p = 0.08) Patients on metoclopramide and diabetic more likely to develop TD (p = 0.05)	^[73]
Shafter et al. (2004)	International metoclopramide adverse event reports and US drug-use data	87 case reports	Mean duration of Rx of 753 ± 951 days; 37% used concomitant drugs, 18% had comorbid diseases with TD risk	Not estimableIncreased use of metoclopramide afer cisapride withdrawal	^[16]
Kenney et al. (2008)	Observational study in a tertiary-care movement-disorder clinic	434 patients referred for TD	Metoclopramide accounted for 39.4% of TD, the second-leading cause of TD after haloperidol	Not estimable	^[72]

EPS: Extrapyramidal side effects; TD: Tardive dyskinesia; VA: Veterans administration.
Adapted from ^{[14,16,64,65,71–74]}.

Box 1. Effects of metoclopramide.
Gastric motility D₂receptor antagonist Stimulation 5-HT₄receptors Muscarinic receptor antagonist Symptoms of gastroparesis Promotes gastric emptying Anti-emetic effects via central pathways Normalization of gastric slow wave dysrhythmias Modulates visceral hypersensitivity

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Metoclopramide in the Treatment of Diabetic Gastroparesis

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