What is the treatment for gastroparesis caused by Ozempic (semaglutide)?

Treatment of Gastroparesis Due to Ozempic (Semaglutide)

The first and most critical step is to discontinue or reduce the dose of Ozempic (semaglutide), as GLP-1 receptor agonists directly cause delayed gastric emptying and withdrawing these medications can improve intestinal motility. 1, 2

Immediate Medication Management

Discontinue the Causative Agent

• Stop or significantly reduce semaglutide, as GLP-1 receptor agonists are known to delay gastric emptying—semaglutide specifically delays first-hour gastric emptying and this mechanism directly contributes to gastroparesis symptoms 1, 2, 3
• Balance this decision against glycemic control needs, but prioritize symptom resolution since medication-induced gastroparesis may be reversible 2, 4
• Review and discontinue other medications that worsen gastric motility, including opioids, anticholinergics, tricyclic antidepressants, and possibly DPP-4 inhibitors 1, 2

Dietary Modifications (First-Line Therapy)

• Implement a low-fat (<30% of total calories), low-fiber eating plan with 5-6 small frequent meals daily instead of 3 large meals 1, 2
• Replace solid foods with liquids such as soups and prioritize liquid calories to minimize gastric distension 1, 2
• Choose foods with small particle size, which can improve key symptoms 1, 2
• Focus on complex carbohydrates and energy-dense liquids in small volumes 2

Pharmacologic Management for Persistent Symptoms

Antiemetic Therapy

• Use 5-HT3 receptor antagonists as the primary pharmacologic approach: ondansetron 4-8 mg twice or three times daily, or granisetron 1 mg twice daily 1, 4
• Phenothiazines (prochlorperazine, promethazine) can be used for nausea and vomiting on an as-needed basis 1

Prokinetic Agents (Use With Extreme Caution)

• Metoclopramide 10 mg three times daily before meals is the only FDA-approved medication for gastroparesis, but should be limited to ≤12 weeks due to FDA black box warning for tardive dyskinesia 1, 2, 5
• Reserve metoclopramide only for severe cases unresponsive to other therapies, given the risk of extrapyramidal signs including acute dystonic reactions, drug-induced parkinsonism, akathisia, and tardive dyskinesia 1
• Erythromycin may be considered but is only effective short-term due to tachyphylaxis 1

Management of Refractory Cases

Neuromodulators for Visceral Pain

• Consider tricyclic antidepressants (nortriptyline 25-100 mg/day preferred over amitriptyline due to fewer side effects) or duloxetine 60-120 mg/day for visceral pain management 4
• Gabapentin (>1200 mg/day in divided doses) or pregabalin (100-300 mg/day) are anticonvulsant options for pain control 4

Nutritional Support

• For patients unable to maintain adequate oral intake (below 50-60% of energy requirements for more than 10 days), jejunostomy tube feeding is the preferred route 2, 4
• Target 25-30 kcal/kg/day and protein intake 1.2-1.5 g/kg/day for severe gastroparesis with malnutrition 2
• Never place gastrostomy (PEG) tubes in gastroparesis patients, as they deliver nutrition into the dysfunctional stomach and worsen the problem 2

Advanced Interventions

• Consider endoscopic injection of botulinum toxin A into the pyloric sphincter, gastric per-oral endoscopic myotomy (G-POEM), or gastric electrical stimulation for refractory symptoms 1, 4

Critical Pitfalls to Avoid

• Do not continue metoclopramide beyond 12 weeks without careful reassessment due to cumulative tardive dyskinesia risk 1, 2
• Do not overlook that semaglutide-induced gastroparesis may be reversible upon discontinuation—this is fundamentally different from diabetic gastroparesis 2, 6
• Avoid synthetic cannabinoids (dronabinol, nabilone) and scopolamine, which can paradoxically worsen symptoms through anticholinergic effects and delayed gastric emptying 4
• Delaying jejunal tube feeding beyond 10 days of inadequate intake can significantly worsen outcomes 2