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Abnormalities in the function of the stomach in patients with long-standing diabetes mellitus, usually insulin-dependent, may provide difficult management problems. There is a reduced frequency of peptic ulcer disease in diabetics. Gastric atrophy, often with parietal cell antibodies, is common and the frequency of pernicious anemia with its expected intrinsic factor antibodies is increased. Gastric analysis results have been conflicting but generally suggest that long-standing diabetics have lower acid levels than normals, possibly secondary to vagal neuropathy. Gastric atony occurring in a small but significant number of patients with longstanding insulin-dependent diabetes, usually with a clinically apparent peripheral neuropathy, has been associated with upper abdominal discomfort, vomiting, and a clinical picture of gastric outlet obstruction. Various degrees of subclinical delays in gastric emptying are probably present in many asymptomatic patients and, indeed, are underemphasized contributors to poor control of blood sugar levels. Studies utilizing radioactive-labeled physiological meals have demonstrated abnormalities in the gastric emptying of solids, in particular, and sometimes liquids in the latter stages of the disease. Metoclopramide, a dopamine antagonist, which stimulates upper gastrointestinal smooth musculature, results in accelerated gastric emptying; clinical trials have shown that it is capable of alleviating symptoms related to diabetic gastroparesis and with its recent approval and release in this country, it promises improved management of this entity. Another agent, domperidone, a selective peripheral dopamine antagonist with no appreciable side effects, is in this country an investigational drug which has shown clinical efficacy in Europe in improving gastric stasis syndromes.

The aims of our study were to: determine the effect of metoclopramide parenterally and orally on delayed gastric emptying of a radionuclide test meal in symptomatic patients with diabetic gastroparesis not explained by ulceration or other mechanical problems; and evaluate in a double-blind crossover fashion the efficacy of metoclopramide in relieving the symptoms of diabetic gastroparesis. Thirteen patients with subjective evidence of gastric stasis had delayed gastric emptying of an isotope-labeled semisolid meal which was significantly accelerated (p less than 0.05) after 10 mg of metoclopramide parenterally. Patients then received metoclopramide 10 mg and placebo before meals and prior to retiring for 3 weeks in a randomized double-blind crossover design. During metoclopramide therapy nausea, vomiting, anorexia, fullness, and bloating were significantly (p less than 0.05) ameliorated compared to placebo with an overall mean symptom reduction of 52.6%. Gastric emptying studies after completion of the trial is seven patients, subjectively improved and receiving open-labeled metoclopramide, showed significantly less gastric retention. Individual improvements in gastric emptying after parenteral or oral metoclopramide, however, could not be correlated with symptom change during the treatment trial. We conclude that metoclopramide is an important therapeutic adjunct in the management of diabetic gastroparesis and its therapeutic effects are mediated through its prokinetic properties as well as centrally mediated antiemetic actions.

Plasma levels and blood pressure responses to two dosage regimens of phenylpropanolamine (PPA)-25-mg, immediate-release tablets three times per day and a 75-mg, controlled-release capsule once per day--were compared in 14 normal subjects. To obtain steady-state conditions, subjects were given the test materials for four-day periods, and blood pressure and plasma PPA levels were measured on day 4. The dosage forms were equally bioavailable, based on a 95-percent confidence coefficient, and neither produced hypertensive effects. The highest diastolic pressure was 96 mm Hg three hours after a 25-mg dose. Mean PPA plasma levels showed no correlation with mean blood pressure readings at any point during a 12-hour test period. These data show that, in these subjects, a daily dosage of PPA 75 mg, either in divided doses of 25 mg each or in a dependable controlled-release formula, produces no indication of pressor effects.