Which medications are known to slow gastric emptying?

Medications That Delay Gastric Emptying

GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide, tirzepatide) are the most clinically significant medications that delay gastric emptying, with documented associations to increased pulmonary aspiration risk during anesthesia and endoscopy. 1

Primary Medication Classes

GLP-1 Receptor Agonists and GIP Agonists

• Semaglutide (Ozempic/Wegovy), liraglutide, dulaglutide (Trulicity), and tirzepatide (Mounjaro) all delay gastric emptying through vagal nerve-mediated mechanisms 1
• These agents activate nitrergic and cyclic adenosine monophosphate pathways to inhibit vagal activity on the gut, resulting in reduced phasic gastric contractions, delayed gastric emptying, reduced gastric acid secretion, and increased fasting and postprandial gastric volumes 1
• The European Medicines Agency Pharmacovigilance Risk Assessment Committee has highlighted that gastric emptying is delayed in people taking GLP-1 RAs 1
• Scintigraphy studies (the gold standard for measuring gastric emptying) have demonstrated delayed gastric emptying in patients with diabetes and obesity on exenatide, liraglutide, and semaglutide 1
• Clinical significance: One study reported an odds ratio of 10.23 (95% CI: 2.94–35.82) for pulmonary aspiration in the elective surgical setting, and a hazard ratio of 1.33 (95% CI: 1.02–1.74) in the endoscopy setting 1

Opioid Analgesics

• All opioid medications can induce pyloric dysfunction and gastric stasis and represent a common, iatrogenic, and potentially reversible cause of gastroparesis 1
• Opioids directly impair gastrointestinal motility and should be withdrawn in gastroparesis patients, with alternative pain management options such as tricyclic antidepressants, SNRIs, or anticonvulsants used instead 2
• Opioid use is an absolute contraindication to gastric electrical stimulation therapy for gastroparesis 3

Anticholinergic Medications

• Anticholinergics delay gastric emptying by reducing gastric motility 1, 4
• Aerosolized atropine has been shown to prolong mean gastric half-emptying time (112 ± 59 minutes) compared with placebo (65 ± 34 minutes), with dry mouth and decreased salivation correlating with delayed gastric emptying 5
• Anticholinergic side effects of medications can include prolonged gastric emptying, suggested by the symptom of dry mouth 5

Pramlintide (Amylin Analog)

• Pramlintide (Symlin) slows gastric emptying and is contraindicated in patients with confirmed diagnosis of gastroparesis 6
• Pramlintide is not recommended for patients taking other medications that alter gastrointestinal motility 6
• Concomitantly administered oral medications should be given at least 1 hour prior to pramlintide injection or 2 hours after, particularly if rapid onset or threshold concentration is critical for effectiveness (such as analgesics, antibiotics, and oral contraceptives) 6

Other Medication Classes

• Tricyclic antidepressants can reduce gastric emptying, though they are sometimes used as symptom modulators in gastroparesis (they reduce symptoms but do not improve gastric emptying) 7
• Narcotic analgesics influence the rate of gastric emptying and can change the rate of absorption of other drugs 4
• Ganglion blocking drugs and alcohol also influence gastric emptying rates 4

Important Clinical Considerations

Tachyphylaxis and Duration of Exposure

• The effects of GLP-1 receptor agonists on gastric emptying vary according to frequency and duration of exposure 1
• Acute and intermittent infusions of GLP-1 receptor agonists have a more pronounced effect on delaying gastric emptying than continuous infusion, suggesting tachyphylaxis develops with prolonged exposure 1
• Two studies using short-acting liraglutide (6 weeks) reported delayed gastric emptying, whereas two studies using long-acting semaglutide (12–20 weeks) showed no delay, suggesting tachyphylaxis had developed 1
• However, patients still had significantly delayed gastric emptying after the second meal despite tachyphylaxis to vagal suppression 1
• There is less certainty regarding the risk of pulmonary aspiration in people using GLP-1 RAs long-term, particularly because the effect of tachyphylaxis on gastric emptying is unclear 1

Perioperative Management

• The American Society of Anesthesiologists recommended that GLP-1 RAs should be stopped either the day before the procedure (for once-daily doses) or the week before (for weekly injections) to minimize the risk of incomplete gastric emptying leading to pulmonary aspiration on induction of anesthesia 1
• Several factors must be considered, including drug characteristics, individual patient profile, the procedure, and the anaesthetic technique, as well as the adverse impact of drug cessation 1

Drug-Drug Interactions

• Many commonly prescribed combinations in gastroparesis patients are predicted to cause potential drug-drug interactions, as many co-administered drugs are metabolized via common drug metabolizing enzymes 8
• Medications that delay gastric emptying can alter the rate of absorption of other orally administered drugs, potentially resulting in therapeutic failure, especially if the drug has a short biological half-life 4