What are the considerations for a patient with gastric paresis starting a Glucagon-like peptide-1 (GLP-1) receptor agonist, such as liraglutide (Victoza) or dulaglutide (Trulicity)?

Critical Contraindication: GLP-1 Receptor Agonists Should Be Avoided in Gastroparesis

GLP-1 receptor agonists are explicitly contraindicated in patients with gastroparesis and should not be initiated in your patient. 1

Primary Concern: Worsening Gastric Emptying

The fundamental mechanism of GLP-1 receptor agonists directly conflicts with gastroparesis:

• GLP-1 RAs slow gastric emptying as a core pharmacologic effect, which is therapeutic for diabetes and weight loss but harmful when gastric emptying is already impaired 1, 2
• The FDA label for dulaglutide explicitly states: "TRULICITY has not been studied in patients with preexisting gastroparesis. Use TRULICITY with caution in patients with gastroparesis" 2
• Current guidelines from the American College of Cardiology (2020) state: "Avoid in patients with diabetic gastroparesis" 1
• The 2024 Anaesthesia guideline explicitly lists "Avoid in gastroparesis" as the management recommendation for nausea and vomiting side effects 1

Clinical Evidence of Harm

Real-world case reports demonstrate the risk:

• Case reports document new-onset gastroparesis symptoms after initiating liraglutide, even at low doses (0.6 mg), with gastric dilatation on imaging and symptom resolution only after drug discontinuation 3, 4
• One study showed that GLP-1 RAs prolonged gastric half-emptying time in nearly all patients without pre-existing gastroparesis, though interestingly showed minimal worsening in those with established gastroparesis 5

Gastrointestinal Adverse Event Profile

The GI side effect burden is substantial and particularly problematic in gastroparesis:

• Nausea occurs in 40% of patients on liraglutide (vs 14.8% placebo), and vomiting in 16% (vs 4.3% placebo) 1
• Semaglutide carries the highest risk among GLP-1 RAs for nausea (ROR 7.41), vomiting (ROR 6.67), and constipation (ROR 6.17) 6
• Liraglutide has the highest severe adverse event rate for GI complications at 23.31% 6
• Most GI adverse events occur within the first month of treatment 6

Psychiatric Patient-Specific Considerations

For your psychiatric patient, additional concerns include:

• Nausea and vomiting can significantly impact medication adherence for psychiatric medications, potentially destabilizing mental health
• GI distress may be misattributed to psychiatric medications, leading to inappropriate medication adjustments
• The delayed gastric emptying effect persists even at physiological GLP-1 concentrations due to the long half-life of these agents 7
• If the patient requires procedural sedation or anesthesia (relevant for psychiatric procedures like ECT), retained gastric contents pose aspiration risk 7

Procedural and Anesthesia Risks

Should your patient require any procedures:

• Retained gastric contents at endoscopy or general anesthesia are more frequent with GLP-1 RAs, creating pulmonary aspiration risk 7
• The long half-lives of these medications (days to weeks) mean simply holding doses before procedures may be insufficient 7
• Point-of-care ultrasound for gastric content assessment and prokinetic agents like erythromycin may be needed 7

Alternative Management Strategy

Strongly recommend discontinuing the GLP-1 RA and pursuing alternative therapies:

• For diabetes management: Consider SGLT-2 inhibitors, DPP-4 inhibitors, or insulin regimens that don't impair gastric motility
• For weight management: Consider phentermine-topiramate ER or naltrexone-bupropion ER if weight loss is the primary indication 1
• Optimize gastroparesis management first with prokinetic agents (metoclopramide, domperidone where available) before considering any medications that slow gastric emptying
• Address the underlying cause of gastroparesis (diabetic neuropathy, medication-induced, etc.)

If Continuation Is Absolutely Necessary (Against Recommendation)

Should there be compelling reasons to continue despite the contraindication:

• Start at the absolute lowest dose and titrate extremely slowly over months, not weeks 1
• Monitor closely for worsening gastroparesis symptoms (early satiety, bloating, nausea, vomiting, abdominal pain)
• Consider gastric emptying studies before and after initiation to objectively assess impact
• Educate patient to report symptoms immediately and maintain low threshold for discontinuation
• Reduce meal sizes significantly and avoid high-fat foods 1
• Coordinate closely with gastroenterology for gastroparesis management

However, the evidence strongly supports avoiding GLP-1 RAs entirely in this clinical scenario. 1, 2