AGA releases updated gastroparesis guideline
The guideline panel "critically assessed the studies available for diagnosing gastroparesis and the treatments used for gastroparesis."
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09/22/2025
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by Amy Pfeiffer
AGA has issued a new guideline with 12 conditional recommendations on the diagnosis and management of gastroparesis.
"This AGA guideline critically assessed the studies available for diagnosing gastroparesis and the treatments used for gastroparesis," noted panel authors. "Overall, there is still considerable unmet need in the treatment of gastroparesis and the need for carefully performed randomized trials to evaluate efficacy of treatments."
New recommendations address diagnostic testing, pharmacologic treatments, and procedural interventions, to provide clarity on best practices.
Diagnosis
Kyle Staller, MD, of the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, and panel colleagues made a conditional recommendation to avoid the two-hour gastric emptying testing and to use four-hour testing to establish a diagnosis.
Data from over 4,000 patients showed that the two-hour test had a sensitivity of only 57%, resulting in a false-negative rate of approximately 12%. A shortened test risks both underdiagnosis and overdiagnosis, leading either to untreated symptoms or unnecessary treatment. The longer testing increases the number of identified cases by 25%.
Validated meal types for scintigraphy include a standardized egg-white meal (“EggBeaters”) that includes liquid egg whites, two slices of toast with jelly, and a glass of water. The second meal (real eggs protocol) consists of the consumption of two eggs with toast and skim milk. Breath testing with 13C-spirulina was also recognized as an alternative with high reproducibility and no radiation exposure, though limitations exist in patients with liver, lung, or malabsorption disease.
Pharmacologic Treatment
Metoclopramide remains the primary pharmacologic option for treating gastroparesis. The panel recommended short-term therapy of up to 12 weeks.
Seven trials demonstrated improvements in nausea, vomiting, and composite symptom scores, although most were small and decades old. More recent studies using intranasal formulations also showed benefit. The panel noted heterogeneity in trial quality but concluded that the totality of evidence supports use.
Adverse effects, including neurologic side effects (confusion and restlessness) and gastrointestinal (nausea and diarrhea) limit long-term use. The therapy contains an FDA black box warning for tardive dyskinesia. However, recent research has shown that the side effect occurs in less than 1% of patients, including those using the drug for a median of 490 days.
The panel issued a conditional recommendation for erythromycin based on evidence of improved gastric emptying and symptom relief.
Erythromycin reduced GCSI-DD by 0.81 points compared to placebo, exceeding the threshold for clinical relevance.
However, tachyphylaxis develops quickly with continuous use due to motilin receptor internalization. The panel noted that “these drugs are often administered for a limited period of time with drug holidays.” Safety concerns include QT prolongation, hepatotoxicity, and drug–drug interactions via CYP3A4 inhibition.
The panel issued conditional recommendations against routine first-line use of several pharmacologic agents:
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Domperidone – Small trials showed symptom reduction, but effects did not meet thresholds for clinical significance. Observational studies also linked use to a small but increased risk of sudden cardiac death. Domperidone is not available in the United States outside of investigational access.
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Prucalopride – Two crossover trials showed numerical symptom improvement, particularly in idiopathic gastroparesis, but results did not reach minimal important difference thresholds. Safety signals included adverse events and psychiatric side effects.
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Aprepitant (NK-1 receptor antagonist) – One randomized trial showed small improvements in nausea and abdominal pain, but benefits were not clinically meaningful, so use is not recommended.
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Nortriptyline – In a randomized trial, nortriptyline failed to improve nausea, vomiting, or overall severity scores. Risks included increased adverse events and treatment discontinuation.
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Buspirone – One trial showed no meaningful improvements in symptoms, though subgroup analysis suggested possible benefit for severe bloating.
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Cannabidiol (CBD) – A single small trial demonstrated reductions in vomiting and early satiety, but the panel withheld a positive recommendation due to concerns about variable formulations, hyperemesis risk, and lack of long-term safety data.
Procedural Interventions
G-POEM was evaluated in one sham-controlled trial and one comparative trial against botulinum toxin injection. Benefits included reduced nausea, vomiting, and postprandial fullness scores at three and six months.
The panel noted selective use in refractory patients may be beneficial; however, procedural risk must be weighed.
The “recommendation seemingly contrasts with the results of numerous observational studies, which suggest benefit of G-POEM,” noted guideline authors. However, they were excluded “due to the high risk of bias.”
Four crossover trials compared GES with the stimulator on versus off. While some reduction in vomiting frequency and nausea were observed, improvements did not reach clinical significance thresholds. Serious adverse events occurred in 7% of patients. The panel suggested against routine initial use.
“Gastric electric stimulation treatment for gastroparesis should be reserved for select patients with medically refractory gastroparesis, particularly those with nausea and vomiting,” they noted.
Two randomized sham-controlled trials and one comparative trial found no clinically important improvement in overall severity scores with pyloric botulinum toxin injection. The panel therefore suggested against routine use, though acknowledged ongoing off-label use in predicting G-POEM response.
Surgical Pyloric Interventions
Evidence for surgical pyloromyotomy and pyloroplasty was limited to observational studies with high risk of bias. The panel did not issue a recommendation, identifying this as an area of knowledge gap.
Practical Implementation
The panel emphasized a multidisciplinary approach for patients with refractory disease. Key considerations include:
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Optimizing glycemic control in diabetes-associated gastroparesis
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Reviewing and discontinuing medications that impair motility (e.g., opioids, GLP-1 receptor agonists)
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Utilizing dietary modification with low-fat, small-particle meals before or alongside pharmacologic interventions
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Using antiemetics (ondansetron, promethazine, prochlorperazine) for symptomatic relief, though they do not affect gastric emptying
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Assessing treatment efficacy at 4 to 8 weeks to guide continuation or adjustment
Health Equity and Access
The panels also highlighted disparities in care. A study cited within reported that “patients who were Black, uninsured, and/or hospitalized in rural setting were less likely to receive surgical treatments for gastroparesis.” The panel noted the need for equitable access to advanced interventions.
The guideline authors were vetted for conflicts of interest. None were disclosed.
Source: Gastroenterology
Summary content
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The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.