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:

• 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.

• 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.

• 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.

• Nortriptyline – In a randomized trial, nortriptyline failed to improve nausea, vomiting, or overall severity scores. Risks included increased adverse events and treatment discontinuation.

• Buspirone – One trial showed no meaningful improvements in symptoms, though subgroup analysis suggested possible benefit for severe bloating.

• 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:

• Optimizing glycemic control in diabetes-associated gastroparesis

• Reviewing and discontinuing medications that impair motility (e.g., opioids, GLP-1 receptor agonists)

• Utilizing dietary modification with low-fat, small-particle meals before or alongside pharmacologic interventions

• Using antiemetics (ondansetron, promethazine, prochlorperazine) for symptomatic relief, though they do not affect gastric emptying

• 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