Domperidone. A review of its use in diabetic gastropathy.

Domperidone is a selective antagonist at peripheral dopamine D2 receptors, with gastroprokinetic and antiemetic properties. It increases the frequency and duration of antral and duodenal contractions, thus decreasing/improving transit time of food through the gastrointestinal tract. Gastric emptying of liquids and solids is significantly improved with oral domperidone 40 to 120 mg/day in patients with diabetic gastropathy. Oral domperidone 40 to 80 mg/day significantly decreased the severity of symptoms of gastropathy from baseline values in 66 to 88% of patients with type 1 (insulin-dependent) or insulin-requiring diabetes mellitus. Double-blind withdrawal of domperidone from patients who had responded previously led to greater deterioration of symptoms in patients with delayed gastric emptying than in those who continued receiving the drug. Quality of life was significantly improved in patients who showed a symptomatic response to domperidone. The administration of domperidone 40 to 120 mg/day significantly reduced hospitalisation rates in patients with gastropathy. The symptomatic improvement with domperidone 80 mg/day was similar to that seen with cisapride 40 mg/day or metoclopramide 40 mg/day, and therapeutic benefits seen in symptoms of gastropathy were maintained with domperidone for up to 12 years. Domperidone 40 to 80 mg/day may be effective in patients who are refractory to metoclopramide, and a combination of domperidone 80 mg/day with cisapride 80 mg/day may improve some symptoms in patients who do not respond to either agent alone. Domperidone 40 to 120 mg/day was well tolerated for periods up to 12 years in trials in patients with diabetic gastropathy. Adverse events with domperidone 80 mg/day were similar to those seen in placebo recipients and significantly fewer than in patients receiving metoclopramide 40 mg/day. Although significant elevation of plasma prolactin levels (unrelated to dosage and duration of treatment) occurred in all domperidone recipients, prolactin-related adverse events were observed in only 10 to 20% of patients.

CONCLUSIONS

The available data suggest that domperidone 40 to 80 mg/day is an effective agent for the management of symptoms of gastropathy in patients with type 1 diabetes mellitus. In addition, it may provide symptom improvement in patients with gastropathy refractory to other gastroprokinetic agents. Domperidone maintains efficacy in the long term (up to 12 years) and appears to have a better tolerability profile than metoclopramide 40 mg/day.