The American Gastroenterological Association (AGA) last fall released new clinical guidance on managing gastroparesis, a complex motility disorder with many unmet therapeutic needs.

The overall standardized prevalence of gastroparesis has been estimated at 267.7 per 100,000 US adults, whereas the prevalence of definitive gastroparesis is just 21.5 per 100,000. Gastroparesis symptoms of pharmacologic origin are becoming more prevalent because of the widespread use of GLP-1 receptor agonists for diabetes and weight loss. These agents can delay gastric emptying, which may pose risks for surgical patients.

The clinical practice guideline, published in Gastroenterology, aims to ensure accurate diagnosis and evidence-based treatments for patients with idiopathic gastroparesis or gastroparesis related to diabetes.

The AGA guideline panel agreed on 12 conditional recommendations.

Salient among these:

• A 4-hour gastric emptying test is needed for accurate diagnosis. A conditional recommendation was issued against the commonly used 2-hour test.
• The dopamine receptor agonist metoclopramide and the macrolide antibiotic erythromycin are appropriate for first-line pharmacologic treatment. Other treatments require shared patient-physician decision-making.
• Conditional recommendations were issued against the use of domperidone, prucalopride, aprepitant, nortriptyline, buspirone, and cannabidiol as first-line therapies.
• Conditional recommendations were issued against routine initial use of gastric per-oral endoscopic pyloromyotomy (G-POEM) or gastric electrical stimulation, reserving these for select patients with symptoms refractory to medical therapies.
• No recommendation was issued regarding the use of surgical pyloromyotomy and surgical pyloroplasty, procedures with knowledge gaps in their use for treatment for gastroparesis.

“There are currently two big drivers for this guidance: the need to standardize diagnosis — shorter gastric emptying tests remain common despite better sensitivity with 4-hour protocols — and a clearer read on which pharmacologic and procedural options actually help versus those we should de-emphasize,” first author Kyle D. Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital in Boston, told Medscape Medical News. “The guideline synthesizes the last decade of trials and pragmatic experience into 12 conditional recommendations, with an explicit push toward 4-hour gastric emptying scintigraphy and more disciplined first-line drug choices.”

Staller identified three gaps that the guideline will have most impact on filling, the first being diagnostic inconsistency. “The 2-hour test misses a meaningful fraction of delayed emptying, so the panel favors 4 hours to reduce false negatives and over-labeling idiopathic dyspepsia as normal emptying.”

Second, the guideline critically appraises pharmacotherapy evidence for better shared decision-making conversations between providers and patients given the variety of options with still limited evidence on benefits and harms.

Third, it assesses procedural options “while making sure that enthusiasm for treatment for a sometimes disabling condition is balanced by a standardized and rigorous approach to what we know and what we still need to learn,” Staller said. “In everyday practice, we still see shortened gastric emptying protocols, liberal off-label use of pharmacologic agents with limited evidence, and rapid escalation to procedural therapies in refractory patients. The AGA guideline departs from that variability.”

In terms of medication options, he added, “What’s different here is the strength of the negative guidance.” Despite their common use, the panel suggests against domperidone and prucalopride as first-line treatments and also against the up-front use of several symptom-modulating agents such as nortriptyline and buspirone. “That’s a shift from earlier practice patterns and older guidance that were more permissive, particularly regarding domperidone, where available.”

On the feedback front, the AGA panel received an unprecedented number of public comments on the initial draft, particularly on its suggestion against domperidone as a first-line agent. “The panel took these comments seriously,” Staller said. “Many providers and patients were worried that our recommendations were too negative and therefore left few options for treatment.”

He noted that there will likely be controversy about the more conservative approach to procedures such as G-POEM and electrical stimulation.

“Our messaging is not that these are without merit in some patients, but that the level of evidence and the potential harms are such that they are not universally beneficial for all gastroparesis patients,” he said. Overall, the recommendations should improve the outlook for patients with better diagnostic sensitivity and a focus on evidence-based initial medications to simplify regimens and patient expectations.

“Curbing premature procedures will spare patients low-yield interventions with significant potential harms while concentrating referrals for those most likely to benefit,” Staller added.

Offering a non-panelist’s perspective on the guidance, Allen A. Lee, MD, MS, assistant professor of internal medicine at the University of Michigan in Ann Arbor, Michigan, agreed the recommendations should benefit patients and physicians by providing clearer advice on diagnosis and treatment. “They outline a step-by-step approach to treatment and highlight certain medications such as metoclopramide and erythromycin as possible first-line options, while also emphasizing that many recommendations are conditional and should be tailored through shared decision making between patients and doctors and providers.”

On the controversy side, Lee added, although the guideline supports short-term use of metoclopramide, this drug carries a black box warning for risk for tardive dyskinesia, and many clinicians are cautious about using it. “Moreover, the use of metoclopramide is recommended for no more than 12 weeks, while gastroparesis is a chronic condition that typically requires ongoing therapy.”

In addition, the recommendations against routine use of G-POEM, gastric electrical stimulation, and botulinum injection for most patients may be contested by some in the gastroenterology community who have adopted these as effective therapies. “And the recommendation against routine use of such procedures may limit access to them and may be used as justification to limit coverage for them,” Lee said.

Looking ahead, Staller identified several priorities. “We need head-to-head and placebo-controlled trials of new prokinetics and antiemetics with patient-centered endpoints, more well-phenotyped populations, and clearer links between symptom change and gastric emptying metrics,” he said.

Also needed are larger, longer randomized trials of G-POEM vs sham or surgical comparators to provide high-quality data on durability and safety outcomes. Current guidance is cautious because high-quality data remain limited.

Phenotyping and biomarkers require study as well. “We need to identify subgroups based on physiology that truly benefit from pyloric therapies and to refine which patients respond to various mechanisms of action for our available pharmacotherapies,” Staller said, adding that the guideline explicitly underscores substantial unmet treatment needs and the importance of individualized care.

This guideline was sponsored by the AGA. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant for Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Other panelists disclosed having financial relationships with various private sector companies. Lee reported consulting for GSK and Atmo Biosciences.