Management of Diabetes in Patients with Gastroparesis

Introduction

Gastroparesis affects approximately 30-50% of patients with longstanding type 1 or type 2 diabetes, according to the American Diabetes Association 1

The American Diabetes Association recommends administering rapid-acting insulin postprandially, with dose adjustment based on actual food consumed, to better align insulin action with delayed nutrient absorption in diabetic patients with gastroparesis 2
The use of continuous subcutaneous insulin infusion (insulin pump) therapy is recommended when possible, in combination with rapid-acting insulin, to improve glycemic control in diabetic patients with gastroparesis 2
Prioritizing abdominal sites for insulin injection is recommended, as the abdomen has the fastest and most consistent absorption rate, and rotating systematically within the abdomen rather than between different body areas can help prevent lipohypertrophy 3

A low-fiber, low-fat diet with small, frequent meals (5-6 per day) is recommended, with an increased proportion of liquid calories and foods with small particle size, to help manage gastroparesis and improve glycemic control 4, 5
Increase proportion of liquid calories and foods with small particle size to facilitate gastric emptying, according to the American Diabetes Association 6, 7
Implement a stepwise nutritional approach, including transition from solid food with modifications to blended/pureed foods, liquid diet with oral nutritional supplements, and consideration of enteral nutrition via jejunostomy tube for severe cases, can help manage symptoms and maintain adequate nutrition, as recommended by the American Gastroenterological Association 8

The American College of Clinical Endocrinologists recommends being aware that gastroparesis can affect the delivery and absorption of orally administered drugs, resulting in later or fluctuating maximal serum concentrations, and considering alternative medications such as DPP-4 inhibitors which have a neutral effect on gastric emptying 1

The following medications may be used for symptom control in patients with severe gastroparesis:

Medication	Dosing	Indication	Limitations
Metoclopramide	10 mg orally, 30 minutes before meals and at bedtime	First-line prokinetic agent	Tardive dyskinesia, limited to 12 weeks
Erythromycin	40-250 mg orally 3 times daily	Alternative first-line agent	Antibiotic resistance concerns, tachyphylaxis
Phenothiazines	As needed	Antiemetic agent
Trimethobenzamide	As needed	Antiemetic agent
Serotonin (5-HT3) receptor antagonists	As needed	Antiemetic agent
NK-1 receptor antagonists	As needed	Antiemetic agent
Tricyclic antidepressants	As needed	Antiemetic agent
SNRIs	As needed	Antiemetic agent
Anticonvulsants	As needed	Antiemetic agent

Domperidone, a dopamine D2-receptor antagonist, has fewer central nervous system side effects compared to metoclopramide, as it does not readily cross the blood-brain barrier, and may be considered if available, with a starting dose of 10 mg three times daily, and requires cardiac monitoring due to QT prolongation risk 8, 9

Maintaining near-normal glycemic control is crucial to prevent the progression of gastroparesis, and adjusting insulin therapy to match carbohydrate intake is recommended instead of reducing food/carbohydrate intake to manage hyperglycemia 4, 6, 1, 10
Optimal glycemic control is recommended for patients with diabetes and severe gastroparesis, with consideration of DPP-4 inhibitors which have a neutral effect on gastric emptying, as recommended by the American Diabetes Association 11, 12

Gastric electrical stimulation (GES) is an FDA-approved surgical intervention for treating refractory gastroparesis that significantly improves nausea and vomiting symptoms in patients who have failed standard medical therapy, though it does not accelerate gastric emptying, as recommended by the American Gastroenterological Association 8
GES is specifically indicated for patients with medically refractory gastroparesis who have failed standard therapy, with predominant symptoms of nausea and vomiting, and not dependent on opioid medications, primarily those with diabetic or idiopathic gastroparesis 8, 5
Contraindications for GES include predominant abdominal pain as the main symptom, current opioid use, and very prolonged, intractable symptoms 8
Gastric peroral endoscopic myotomy (G-POEM) may be considered for patients with severe delay in gastric emptying, with a strength of evidence level of low, as recommended by the American Gastroenterological Association and the American Society for Gastrointestinal Endoscopy 8, 13, 14
Enteral nutrition via jejunostomy tube may be considered when oral intake is inadequate in patients with severe gastroparesis, with a strength of evidence level of moderate, as recommended by the European Society for Clinical Nutrition and Metabolism 14

The National Institute of Diabetes and Digestive and Kidney Diseases is investigating ghrelin receptor agonists, serotonergic agents, and NK-1 receptor antagonists as potential future alternatives for patients with refractory gastroparesis symptoms, with a strength of evidence level of very low 14
Prucalopride is a highly selective 5-HT4 receptor agonist that promotes neurotransmission by enteric neurons, stimulates the peristaltic reflex, enhances intestinal secretions and GI motility, and induces and increases the amplitude of colonic high-amplitude propagated contractions, with a recommended dose of 1 mg daily in patients with severe renal impairment (creatinine clearance <30 mL/min) 15