Differing professional viewpoints, a lack of diagnostic standards, and regulatory roadblocks to new medications are among the factors hindering progress in treating people with gastroparesis, but there are some signs of movement. 

Gastroparesis is currently defined by delayed gastric emptying of solid food without mechanical obstruction. Symptoms include post-meal fullness, early satiety, nausea, vomiting, and upper abdominal pain. Many cases are idiopathic, but a large number are drug associated or occur in people with diabetes or post-surgery. A majority of patients are female. 

Gastric emptying scintigraphy (GES) is the gold standard for diagnosing gastroparesis, but in practice the diagnosis is often made without patients undergoing a GES. And even when a GES is done, there is wide variation in the way it’s conducted, leading to heterogeneity in patient populations. 

Two sets of clinical management guidelines have been published: one in 2022 by the American College of Gastroenterology (ACG) and the other in October 2025 by the American Gastroenterological Association (AGA). The AGA held strictly to the data, while the ACG also supplemented with expert consensus when the evidence was deemed insufficient. There has been pushback in the field toward the AGA guideline, with some experts finding fault with its frequent reliance on “shared decision-making” in the absence of definitive data. 

However, both documents reflect the dearth of available treatments. Only one medication, the old antiemetic dopamine antagonist metoclopramide (Reglan oral, Gimoti nasal spray), is approved by the FDA for treating diabetic gastroparesis, and it carries a black box warning about tardive dyskinesia. Other drugs, including anti-emetics and neuromodulators, are used off-label. Surgical and biomechanical approaches are available for refractory cases, with varying efficacy. 

There has also been fundamental disagreement among gastric motility specialists about the condition itself: One view is that gastroparesis is a rare “orphan” disease characterized by a strictly conducted GES using standardized test meal, timing, and stomach content cutoffs. Another says that people with chronic symptoms of fullness, nausea, vomiting, and upper GI pain but in whom the GES is negative — so-called “functional dyspepsia” — actually have variants of the same condition, and that the speed of stomach content emptying is just one of several aspects of so-called “disorders of gut-brain interaction.” 

As currently defined, the prevalence of functional dyspepsia is about 15-fold higher than gastroparesis, which is estimated at about 21.5 per 100,000 when diagnosed with a GES, or about 0.0215% of the US population. But if the two are combined into one disease category based on symptoms, overall US prevalence likely tops 7%. There is currently no FDA-approved drug for functional dyspepsia. 

Linda Nguyen, MD, Chief of Gastroenterology of Hoag Healthcare System’s Digestive Health Institute, Orange County, California, told Medscape Medical News, “The gastric emptying test is only looking at one aspect of the stomach. The stomach is a complex organ, and there can be accommodation and sensory effects. I tend to think of gastroparesis and functional dyspepsia as ‘gastric neuromuscular dysfunction,’ sort of on a spectrum.”

Nguyen, who is also a member of the National Institutes of Health’s Gastroparesis Clinical Research Consortium (GpCRC) and a co-author of the ACG gastroparesis guidelines, said that as there are many causes of congestive heart failure, “the stomach is just as complicated, but we boil it down to just the emptying part, and I think that's why every drug we've studied in the last 30 years has failed to come to market. … When you have a drug that is dealing with just one aspect of gastric function, you're probably missing the mark.”

Kyle Staller, MD, Director, Gastrointestinal Motility Laboratory at Massachusetts Hospital, Boston, and lead author of the AGA guidelines, told Medscape Medical News, “I think the experience of treating patients with gastroparesis is universally frustrating for [clinicians]. … There are a couple of big issues that come up. One is how we define gastroparesis … it’s actually fairly controversial in and of itself … and because of that, there's a lot of heterogeneity in terms of which patients were included in various studies looking at treatments.” 

How Helpful Are the Guidelines? 

The AGA Clinical Practice Guidelines advise using a 4-hour GES to diagnose gastroparesis, rather than a 2-hour test. For first-line treatments, they “suggest” the use of erythromycin and metoclopramide, while advising against off-label use of a longer list of medications as first-line, including buspirone, cannabidiol, domperidone, nortriptyline, and prucalopride.

However, they add that these agents may be used in the context of “shared decision-making” based on patients’ values.

For refractory cases, AGA either “recommends” or “suggests” against botulinum toxin, gastric peroral endoscopic pyloromyotomy (G-POEM), and gastric electrical stimulation, while making no recommendation for or against surgical pyloric interventions (pyloromyotomy or pyloroplasty). But again, the guidance allows for using these in the context of shared decision-making. 

Of note, the AGA document states, “We do not intend for policy makers and insurance companies to use the recommendations in this document for determining treatment coverage.” 

Staller told Medscape, “The evidence right now isn’t very robust for many of the treatments that represent the backbone of what we offer patients. … Essentially, the guidelines tell us this is the state of the evidence. I think we were all disappointed when it was subjected to a rigorous guidelines process. At the same time, I hope it's a call to action to say that we need better definitions and more homogeneous populations enrolled in clinical trials.”

But Nguyen and other members of the NIH consortium believe that the AGA guideline isn’t helpful in its reliance on “shared decision making” in the absence of data for treatments not approved for gastroparesis and after having said that they’re not recommended. “When you say shared decision making, you’re assuming that the patient understands the risks and the benefits? … And if you’re not a gastroparesis expert, are you going to go against the guidelines?” 

For its part, the 2022 ACG Clinical Guideline advises a GES of at least 3 hours and recommends against use of radiopaque markers testing. Both wireless motility capsules and stable isotope breath tests are conditionally advised for evaluating upper gastrointestinal symptoms.

Like the AGA, the ACG also suggests metoclopramide for those in whom small particle diet management and optimal glycemic control in those with diabetes aren’t sufficient. But ACG is more permissive regarding other pharmacologic agents. They “suggest’ using domperidone (where approved), 5-HT4 agonists, and antiemetic agents even if they don’t improve gastric emptying. However, the ACG advises against using central neuromodulators, ghrelin agonists, and haloperidol. 

Unlike the AGA, the ACG says that gastric electrical stimulation, approved as a humanitarian use device, may be considered for gastroparesis symptom control. They endorse acupuncture for diabetic but not idiopathic gastroparesis. Like AGA, they advise against botulinum toxin, but in contrast, ACG “suggests” pyloromyotomy over no treatment for symptom control. 

Should the Condition Be Defined More Narrowly or More Broadly (and Renamed)? 

In a study published in 2022, investigators from Mayo Clinic’s Jacksonville, Florida, center analyzed records from 339 patients (82% female) referred for tertiary evaluation of gastroparesis. Most (89%) had nausea, abdominal pain (76%), and vomiting (66%), while some had bloating (37.5%) and early satiety (34.5%). Only 58% had undergone a GES, and of those, only 38% had 4-hour tests and only 7% ingested radiolabeled eggs as the test meal. 

Overall, only 19.5% of the patients were ultimately confirmed to have gastroparesis, while 80.5% received other diagnoses, most often functional dyspepsia (44.5%). The authors referred to these patients as having been misdiagnosed. 

However, even when a GES is performed, the wide variation in methodology also leads to misdiagnosis, said Michael Camilleri, MD, DSc, Professor of Medicine, Pharmacology, and Physiology at Mayo Clinic College of Medicine and Science, Rochester, Minnesota. 

Camilleri, who was a co-author on both the AGA and AGC gastroparesis management guidelines, believes stricter criteria for conducting the test would better characterize patients both clinically and for research.

In a review article, Camilleri and colleague Henry P. Parkman, MD, of Temple University, Philadelphia, recommend a higher-fat test meal than is typically used to better mimic Western diets, or, with the current test meal, a 20% cutoff at 4 hours for retained food rather than the current 10%. They also advise abandonment of the use of the wireless capsule to diagnose delayed gastric emptying. 

“The test that's used most commonly is fine, as long as we acknowledge it isn't like a stress test for the stomach and we need to start using a different cutoff to determine normal or delayed,” Camilleri told Medscape Medical News, adding “the capsule does not empty like solid food and many results are false positives.” 

But Pankaj J. Pasricha, MBBS, MD, gastroenterologist and Chair of Internal Medicine at Mayo Clinic, Scottsdale, Arizona, has a more expansive view of the condition causing people to experience the classic symptoms of nausea, vomiting, bloating, excessive fullness, and abdominal pain. 

Pasricha and colleagues published results of a prospective study of 944 patients, including 720 (76%) with gastroparesis based on GES and 224 (24%) with functional dyspepsia based on the Rome III criteria (for which Camilleri was an author). Symptom type and severity were similar between the two groups. 

At 48 weeks among 249 patients who had a second GES, 42% who previously had a diagnosis of gastroparesis were reclassified as having functional dyspepsia based on GES results, while 37% who previously had been diagnosed with functional dyspepsia now had gastroparesis, again based on the emptying study. Changes in either direction were not associated with any symptom changes. 

“So we have relied for decades on a test that is not really accurate or robust enough to reliably distinguish these conditions,” Pasricha told Medscape Medical News. 

Moreover, full-thickness stomach biopsies conducted in nine individuals from each group (none with diabetes) showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with matched controls. “We found the pathology in the stomach was exactly the same. … We expected to see a difference, but there was no difference. … You cannot distinguish them clinically. The severity is the same. The demographics are the same, about 90% women,” Pasricha said. 

And, he pointed out, “There has not been a single drug that has worked based on simply improving gastric emptying.” 

Pasricha believes that the term “functional” is often interpreted by both clinicians and patients as being psychosomatic. “We have not yet as a profession gotten away from the hysteria terminology. If it's a young woman, you can't find anything just by some tests, then it must be all in the mind. And that is the most stigmatizing, dismissive thing that you can tell a person.”

In 2025, Pasricha, Nguyen, and another colleague authored a commentary arguing for cessation of the term “functional” but also noting that the term “disorders of gut-brain interaction” isn’t specific or understandable to patients. They called for the profession to come together to create a new name for the spectrum disorder. 

Camilleri and others disagree that the two diagnoses are interchangeable. In a 2025 commentary, he and Nicholas J. Talley, MD, of the University of Newcastle, Australia, faulted Pasricha’s study for not using the more stringent GES parameters they recommend and for the possible confounding effect of patients’ use of antidepressants, anxiolytics, and narcotics, all of which can slow gastric emptying. 

Why Aren’t There More Pharmacologic Treatments? 

Despite these differing viewpoints, there is consensus in the field that better treatments are needed for patients with gastroparesis and that FDA requirements for long studies and for multisymptom improvement including motility are part of the problem. In fact, the FDA’s Gastroparesis: Clinical Evaluation of Drugs for Treatment Guidance for Industry was posted as a draft in August 2019 and never finalized, but it’s the only FDA guidance available. 

The FDA advises manufacturers that the primary endpoint should measure change in signs and symptoms from baseline over a treatment period of at least 12 weeks’ duration and that idiopathic and diabetic gastroparesis patients should be studied in separate clinical trials. The FDA also advises that all five signs and symptoms — nausea, vomiting, postprandial fullness, early satiety, and abdominal pain — should be included as trial endpoints, and that all but vomiting should be rated by severity. 

In addition, the FDA document says, “Gastric emptying time should not be used as a primary efficacy endpoint because changes in gastric emptying time are not associated with the changes in the clinically important signs and symptoms in patients with gastroparesis.” 

In their review article, Camilleri and Parkman argue that 12 weeks is too long to observe treatment effects on nausea and vomiting and that trials should be limited to 4 weeks. In addition, they say that manufacturers should be able to investigate and seek approval for their drugs for individual gastroparesis symptoms, particularly nausea/vomiting, based on the drug’s mechanism of action. 

“Nobody has been able to get a drug approved based on that totality of the symptoms. … We can be much more precise and individualize treatment, and we can utilize the pharmacological effect to control that specific type of symptom,” Camilleri commented. 

Camilleri and Parkman also argued that if gastroparesis is strictly defined, its prevalence is low enough to qualify any effective drug for it under FDA’s Orphan Drug designation, typically for diseases that affect fewer than 200,000 people in the US. That would open up additional approval pathways, they said.

With the current FDA requirements, several drugs that had previously been in development for gastroparesis were either denied approval or were withdrawn by their manufacturers. For example, the ghrelin receptor agonist relamorelin both significantly accelerated gastric emptying and reduced vomiting compared to placebo in a phase 2 trial, but Allergan terminated its development “solely based on a business decision.” 

And Neurogastrx, maker of metopimazine/NG101, is no longer developing the drug for gastroparesis after a negative phase 2 trial, although the company is still pursuing it for GLP-1 induced nausea and vomiting. 

Takeda Pharmaceuticals was developing several different candidate drugs for gastroparesis, but a company spokesperson told Medscape Medical News that “at this time, Takeda is not actively pursuing clinical development programs specifically in gastroparesis.” However, one of their drugs, the selective serotonin-4 (5-HT4) receptor agonist prucalopride (Motegrity) had shown promise in treating gastroparesis and is approved in the US for treating chronic idiopathic constipation. 

Similarly, in 2024 FDA declined to approve Vanda Pharmaceuticals’ neurokinin 1 receptor antagonist tradipitant for gastroparesis, but in December 2025 the FDA did approve it under the brand name Nereus for preventing motion sickness-induced vomiting. The company is also studying tradipitant for GLP-1-associated nausea and vomiting. 

In gastroparesis, one trial of tradipitant showed statistically significant reductions in nausea and vomiting, while another didn’t, although there were positive trends. 

Vanda co-founder Mihael H. Polymeropoulos, MD, who serves as company President, Chief Executive Officer, and Chairman of the Board, told Medscape Medical News, “It’s a difficult disorder to run clinical studies on. It had taken us years to be able to recruit patients for the studies. … We showed that tradipitant benefited everything except actual emptying, which is probably the least important thing in terms of patient experience.”

Polymeropoulos has been pushing back on the FDA’s decision not to approve tradipitant for gastroparesis. “I believe that FDA policies have gotten in the way. … This idea that we have to have a 12-week study for every chronic indication is not informed by science,” he said, noting that Vanda has established an expanded access protocol for obtaining tradipitant for some individuals with gastroparesis. 

Despite the barriers, some companies are pushing ahead with candidate gastroparesis drugs. One, CinRx portfolio company CinDome Pharma, is developing deudomperidone (CIN-102) for treating both idiopathic and diabetic gastroparesis. It’s a novel version of the dopamine antagonist domperidone, which is available in some countries for treating gastroparesis but was never approved in the US due to safety concerns about prolonged QT elevation. 

A company representative told Medscape Medical News, “CinDome developed deudomperidone to improve safety without sacrificing domperidone's effectiveness, which offers both prokinetic and antiemetic benefits without anticholinergic activity. Deudomperidone is currently in phase 2 clinical trials, with data readouts expected in 2026.” 

Another company, Renexxion, is developing a dual acting serotonin 5-HT4 receptor agonist and dopamine D2 receptor antagonist pill called naronapride for a variety of gastrointestinal disorders including gastroparesis phase 2b results of the MOVE-IT trial in gastroparesis are expected later in March, a company spokesperson told Medscape Medical News. 

In response to a request for comment, FDA said it “bases approval decisions on whether an application submitted to FDA for approval of the drug shows that it is safe and effective for use under the conditions in its proposed labeling” and that its guidance to industry represents “recommendations” and “not requirements.” In addition, FDA is “open to considering alternative approaches when appropriately supported.”

The bottom line, Staller said: “We need that pipeline to keep flowing so that these patients who are suffering are offered something to help them feel better.”

Staller has consulted for Focus Medical Communications, Retalsis, Anji, and Ardlix. Camilleri has consulted for Sunovion, SKYE Bioscience, Vanda, Takeda; Ad Boards: Phenomix, Enterin, and Phenomix. Linda Nguyen is a consultant for Ardelyx, Phathom, Enterra Medical, AnX Robotic, Novo Nordisk, CinDome, Eli Lilly, Laborie, Alimetry and is on the board of directors of EBMed. Pasricha was the founder and inventor of metopimazine (NG-101) under development by Neurogastrx, is founder of ON Therapeutics, and is a consultant for Vanda Pharmaceuticals. Polymeropoulos is a Vanda employee. 

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social