How does Ozempic (semaglutide) affect gastroparesis?

Ozempic (Semaglutide) and Gastroparesis: Clinical Implications

Semaglutide is contraindicated in patients with clinically meaningful gastroparesis as it may worsen symptoms by further delaying gastric emptying. 1

Mechanism of Action and Effects on Gastric Emptying

• GLP-1 receptor agonists like semaglutide delay gastric emptying through central and peripheral pathways that inhibit vagal activity on the gut 1
• This effect leads to reduced phasic gastric contractions, delayed gastric emptying, reduced gastric acid secretion, and increased fasting and postprandial gastric volumes 1
• The delay in gastric emptying occurs through activation of GLP-1 receptors in the hypothalamus and brainstem nuclei, which modulate appetite, satiety, and gut motility 1

Tachyphylaxis and Duration of Effect

• The effect on gastric emptying varies according to frequency and duration of exposure, with evidence of tachyphylaxis (diminishing response) with continuous exposure 1
• Short-acting GLP-1 receptor agonists tend to have more pronounced effects on gastric emptying than long-acting formulations 1
• Despite tachyphylaxis, studies using scintigraphy (gold standard for measuring gastric emptying) have shown that semaglutide still causes delayed gastric emptying 1
• Acute and intermittent administration has a more pronounced effect on delaying gastric emptying than continuous administration 1

Clinical Implications for Patients with Gastroparesis

• According to American College of Cardiology guidelines, shorter-acting GLP-1 receptor agonists are not recommended in patients with clinically meaningful gastroparesis 1
• While the effect on gastric emptying is usually transient with longer-acting GLP-1 receptor agonists like semaglutide, caution is still warranted in patients with gastroparesis 1
• Case reports have documented instances of semaglutide inducing or worsening gastroparesis symptoms in some patients 2, 3
• Patients with pre-existing bloating, nausea, abdominal pain, and discomfort may experience worsening of these symptoms with semaglutide 2

Perioperative Considerations

• Semaglutide use is associated with increased residual gastric content despite adequate preoperative fasting 4
• In a retrospective analysis, 24.2% of patients taking semaglutide had increased residual gastric content during upper endoscopy compared to 5.1% in non-semaglutide users 4
• There have been reported cases of pulmonary aspiration of gastric contents in patients taking semaglutide for weight loss 5
• Patients taking semaglutide may have a full stomach despite compliance with routine pre-operative fasting guidelines 5, 6

Monitoring and Management Recommendations

• Patients with gastroparesis who are prescribed semaglutide should be closely monitored for worsening of symptoms including nausea, vomiting, early satiety, and abdominal pain 1
• If gastroparesis symptoms worsen with semaglutide, discontinuation of the medication should be considered 2, 3
• For patients with severe or refractory gastroparesis, alternative diabetes or weight management therapies should be considered 1
• Care should also be taken in patients with prior gastric surgery when considering semaglutide therapy 1

Other Considerations

• Gradual dose titration of semaglutide is recommended to minimize gastrointestinal adverse effects 1
• Semaglutide may impact the absorption of some oral medications that require rapid onset of action due to its effect on gastric emptying 1
• Patients with gastroparesis should be evaluated for the dominant refractory symptom to guide management efforts, particularly when considering escalation of medical management 1

In summary, while semaglutide offers significant benefits for glycemic control and weight management, its use in patients with gastroparesis requires careful consideration due to its effects on gastric emptying, which could potentially worsen gastroparesis symptoms.