Metoclopramide in the Treatment of Diabetic Gastroparesis

Allen Lee; Braden Kuo


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

In This Article

Clinical Efficacy

Metoclopramide is approved for short-term use in diabetic gastroparesis. Five controlled trials and four open-label series[13,40–47] have evaluated the efficacy of metoclopramide in the treatment of diabetic gastroparesis. Symptoms improved in seven studies and gastric emptying was accelerated in five studies. The largest study to date was by Patterson et al., who performed a randomized, double-blind multicenter trial on 45 patients with diabetic gastroparesis to compare the efficacy and safety of domperidone versus metoclopramide. Gastroparesis symptom scores as well as adverse CNS effects were evaluated after 2 and 4 weeks. Metoclopramide improved symptoms by 39% but this was not statistically different from domperidone. However, CNS side effects were more pronounced with metoclopramide.[47]

Perkel et al. performed the second-largest trial to date. This was a randomized, double-blind, placebo-controlled study on 28 subjects with gastroparesis secondary to diabetes (n = 5), owing to post-surgical causes (n = 4) and idiopathic causes (n = 19). Symptom scores, including meal tolerance, epigastric pain, postprandial bloating, heartburn, belching and regurgitation, nausea, vomiting, anorexia, and early satiety were evaluated pre-study at weekly intervals and at 4 weeks. Metoclopramide significantly improved the symptoms scores of patients with idiopathic and postsurgical causes of gastroparesis. Overall, symptom scores improved by 29% with metoclopramide, and there was a significantly greater improvement of symptoms scores with metoclopramide compared with placebo (p < 0.05).[42]

Metoclopramide has been demonstrated to be effective for the short-term treatment of gastroparesis for up to several weeks,[13,42] but long-term efficacy has not been proven.[48] Longstreth et al. showed prolonged improvement in symptoms, as well as gastric emptying, in one subject over 6 months.[41] Lata et al. reviewed studies from 1965 to 2002 to investigate the efficacy of chronic metoclopramide therapy. No consistent benefit was observed from the use of metoclopramide for more than 1 month. The longest trial was 6 months in duration and showed improvement in only three patients for 1 month or more. However, these were small, uncontrolled, open-label studies that do not provide sufficient data to determine whether chronic metoclopramide improves symptoms.[48] Gastric emptying has also been demonstrated to improve with short-term administration of metoclopramide, but returned to baseline with long-term dosing for more than 1 month.[49] There was also poor correlation between the acceleration of gastric emptying and symptomatic improvement (coefficient of correlation [r] = 0.09 and 0.29 for parenteral and oral metoclopramide, respectively).[45] However, some patients reported continued symptomatic relief without a prolonged effect on gastric emptying.[48] Thus, symptomatic improvement from metoclopramide may not result entirely from promotility effects, but also from antiemetic effects and potentially from normalization of gastric slow-wave dysrhythmias.[50] Finally, there is some evidence that antidopaminergic agents, specifically domperidone, may modulate visceral hypersensitivity by acting along the brain–gut axis and thus improving pain.[51] Metoclopramide has been demonstrated to improve visceral hypersensitivity in rats, but it is still unclear whether metoclopramide has similar effects in humans.[52]

Metoclopramide has been compared in studies with other promotility agents, including cisapride and domperidone. Cisapride showed significantly improved gastric emptying compared with metoclopramide.[53] However, in a double-blind crossover study between metoclopramide and cisapride, there was no significant difference in symptomatic control. There was a trend towards reduced nausea and vomiting with metoclopramide while cisapride showed a trend towards reduced epigastric fullness.[54] Both metoclopramide and cisapride were most effective in reversing the morphine-induced delay in gastric emptying and small intestinal transit in mice compared with domperidone, erythromycin and mosapride.[55] As mentioned previously, metoclopramide was also compared directly with domperidone in a randomized, double-blind multicenter trial. Metoclopramide and domperidone were found to be equally effective in controlling symptoms from diabetic gastroparesis, but CNS side effects were significantly more pronounced with metoclopramide.[47]


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