Controversies in Care and the Seek for Higher Answers

Gastroparesis, an unusual and sometimes misunderstood motility dysfunction, sits on the crossroads of advanced physiology and restricted therapy choices. Unlike different motility situations, gastroparesis presents distinctive challenges, from misdiagnosis to a shortage of efficient therapies. Its heterogeneity and overlapping signs not solely complicate prognosis but in addition gradual progress in analysis, leaving sufferers with few dependable choices and clinicians trying to find higher solutions.^1,2

“When I think about the field of gastroparesis, the 3 C’s come to mind: challenging, complicated, and controversial,” Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, informed HCPLive, citing challenges associated to each prognosis and therapy, the primary typically attributable to frequent misdiagnoses and incorrectly carried out diagnostic exams.

In 2022, the American Gastroenterological Association (AGA) launched a medical guideline detailing acceptable exams for diagnosing gastroparesis and each pharmacologic and non-pharmacologic therapies for bettering gastroparesis signs and gastric emptying. In this doc, the AGA strongly beneficial scintigraphic gastric emptying of a strong meal with a length of ≥ 3 hours for prognosis of gastroparesis, advising in opposition to shorter research like gastric emptying research, that are solely 90 minutes lengthy, because of the potential for false damaging outcomes.³

“A lot of patients have a normal gastric emptying study, or the gastric emptying study may not have been done correctly,” Douglas Weinstein, MD, a gastroenterologist and director of GI Motility at Hackensack Meridian Jersey Shore University Medical Center, informed HCPLive, describing how the scale and composition of the meal eaten, drugs taken, and affected person place could affect check outcomes. “Even if everything’s done right, sometimes [the test] will still be normal.”

Adeling Hung, MD, a medical assistant professor at Rosalind Franklin University Chicago Medical School and director of the IBD program at Sinai Health System Chicago, added that along with these potential variations in check protocols and subsequent outcomes, beneficial exams like gastric emptying scintigraphy are usually not broadly obtainable outdoors of specialised facilities and don’t pinpoint the first reason behind gastroparesis to find out which therapy could also be most acceptable.

Of notice, the one sturdy therapy suggestions within the 2022 AGA gastroparesis guideline centered on therapies not supported to be used, together with neuromodulators, ghrelin agonists, and intrapyloric botox injections. Conversely, small-particle diets, metoclopramide, domperidone, antiemetic brokers, and 5HT4 agonists are steered for symptom management or enchancment in gastric emptying.³

Currently, the one FDA-approved gastroparesis therapy is metoclopramide, a dopamine receptor antagonist first accredited for diabetic gastroparesis in 1979. In 2020, the FDA accredited Evoke Pharma’s metoclopramide (Gimoti) nasal spray as the primary and solely nasally-administered product indicated for the aid of signs in adults with acute and recurrent diabetic gastroparesis. The approval additionally represented the primary novel pharmaceutical therapy for gastroparesis in a number of a long time.^4,5

However, a number of considerations exist concerning using metoclopramide for gastroparesis. It shouldn’t be beneficial for use for durations longer than 12 weeks, and in 2009, the FDA positioned a Black Box warning on metoclopramide due to the chance of associated unwanted side effects, together with tardive dyskinesia, with persistent or high-dose use.⁶

“Metoclopramide is not a good medicine because it can’t be used long-term,” Weinstein defined. “There is a nose spray that was recently approved, but it has the same side effects as metoclopramide, or even more because it gets absorbed. It could cause neurological side effects that can be permanent if people are on it long term, so we try not to use it.”

Beyond metoclopramide, erythromycin, a macrolide antibiotic used to deal with or forestall a variety of bacterial infections, can also be used off-label to deal with gastroparesis due to its prokinetic results on gastrointestinal motility to stimulate gastric emptying. However, like metoclopramide, erythromycin shouldn’t be an ideal therapy.⁷

“The few approved prokinetics, including metoclopramide and erythromycin, have modest efficacy, short durability, and significant side effects, which are both neurologic and cardiac in nature,” Hung informed HCPLive.

With a extreme unmet want for brand spanking new and efficient pharmacologic therapy choices, Vanda Pharmaceuticals sought so as to add one other novel remedy to the restricted gastroparesis therapeutic panorama with the Company’s New Drug Application (NDA) for tradipitant, a neurokinin receptor 1 antagonist licensed by Vanda from Eli Lilly and Company. However, in September 2024, the FDA issued a Complete Response Letter (CRL) to the NDA, suggesting Vanda conduct extra research with a design and length Vanda described as being inconsistent with the recommendation of key consultants within the discipline and never acceptable based mostly on the scientific understanding and pure course of gastroparesis.⁸

With the CRL, metoclopramide stays the one FDA-approved agent indicated particularly for the therapy of gastroparesis, elevating questions as to how significant progress in bringing efficient gastroparesis therapies to market could be achieved.

“Due to [the heterogeneity of the disease and its] multiple mechanisms, it is hard to find one treatment or therapy that can show appropriate efficacy for all patients… In most trials, you need both improvement of symptoms and of gastric emptying times to demonstrate benefit, but in some cases, a treatment may help clinical symptoms while not meeting gastric emptying endpoints,” Hung defined, citing the necessity for higher classification of sufferers based mostly on mechanism of illness with exams past gastric emptying scintigraphy to extra appropriately examine focused remedy in trials, which she says ought to have extra versatile endpoints and think about patient-reported outcomes.

Beyond considerations about trial design, the elemental definition of what gastroparesis entails is one other space of controversy doubtlessly impacting therapy growth.

“I believe that one of the biggest challenges is that we need to rethink what gastroparesis really is,” Lacy informed HCPLive, describing inherent points with the present mindset that gastroparesis is solely a motor (muscle) dysfunction of the abdomen that may be handled by accelerating gastric emptying. “That may work in some patients, but the data is very clear that it does not work in most patients… If the field is to move ahead, we need to reframe how we think about the underlying physiology of gastroparesis.”

Rather, Lacy factors to the seemingly principle that gastroparesis represents a sensory dysfunction in lots of sufferers, an idea supported by the info displaying that accelerating gastric emptying doesn’t enhance signs in addition to information suggesting a robust overlap between gastroparesis and practical dyspepsia, a dysfunction of intestine mind interplay.

Hung adopts an identical perspective, noting signs don’t all the time correlate with gastric emptying occasions and describing how some sufferers with extreme delays could also be minimally symptomatic whereas others with solely delicate delay are very symptomatic. Because of this, she says bettering gastric emptying occasions doesn’t all the time relieve signs.

Despite not being beneficial within the 2022 AGA steering, within the absence of notable progress concerning pharmacologic therapy choices for gastroparesis, advances in neuromodulation and device-based approaches to care have gained traction, with Hung describing them as “shaping the future of gastroparesis care.”

Among these advances are gastric electrical stimulation and vagal nerve stimulation, each of which have proven promising outcomes for nausea/vomiting and neural management of motility for chosen sufferers. Of notice, the most recent gastric electrical stimulation is programmable to patient-specific parameters and customizable to affected person’s wants, which helps personalize remedy.

For neurostimulation, Weinstein describes how he tries to foretell which sufferers are going to reply effectively by doing a short lived stimulation trial the place the affected person carries a simulator externally for per week or 2 to find out if their signs get higher.

“If their symptoms don’t improve, then we don’t implant the stimulator, and that helps us reduce unnecessary surgery… but it does help a lot of patients by improving electrical activity in the stomach, by improving the vagus nerve function, and by improving brain sensations,” Weinstein stated, describing its utility throughout a number of nausea/vomiting situations past gastroparesis.

However, whereas recognizing the advantage of such approaches, particularly for sufferers that haven’t responded to pharmacological or pyloric therapies, Hung was cautious to name consideration to the necessity for extra standardization on methods to greatest combine the most recent procedures/gadgets together with pharmacological remedy in order that sufferers can obtain the precise remedy on the proper time.

“This could be an exciting area of research in the future. If we begin to view gastroparesis as a sensory disorder for many, but not all, patients, then new treatment pathways will emerge,” Lacy added. “For example, we know that a small subset of patients with gastroparesis respond well to gastric electrical stimulation. Could more selective devices be employed to better improve symptoms? Or, if we consider this a sensory disorder in some, can we employ new medications to help tamp down these overly sensitive nerves which may be the underlying cause of persistent symptoms of nausea and vomiting?”

As the sector continues to grapple with diagnostic complexities, restricted pharmacologic choices, and the evolving understanding of gastroparesis as greater than only a motility dysfunction, the trail ahead would require each innovation and collaboration. Redefining illness mechanisms, incorporating patient-reported outcomes into trial design, and integrating novel device-based approaches alongside pharmacotherapy could assist bridge long-standing therapy gaps.

While progress has been incremental, rising recognition of gastroparesis’ heterogeneity and the push for extra focused, patient-centered methods recommend the following chapter in care might carry significant advances for sufferers who’ve waited a long time for higher options.

Editors’ notice: Hung and Weinstein report no related disclosures. Lacy reviews related disclosures with AbbVie, Bausch, Gemelli, Ironwood, Salix, and Sanofi.

References

1. Mount Sinai. Mount Sinai Center for Gastrointestinal Physiology & Motility. Accessed August 27, 2025. https://www.mountsinai.org/care/gastroenterology/services/motility

2. International Foundation for Gastrointestinal Disorders. Motility Disorders. Accessed August 27, 2025. https://iffgd.org/gi-disorders/motility-disorders/

3. Camilleri M, Kuo B, Nguyen L, et al. ACG Clinical Guideline: Gastroparesis. The American Journal of Gastroenterology. doi:10.14309/ajg.0000000000001874

4. Lee A, Kuo B. Metoclopramide within the therapy of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. doi:10.1586/eem.10.41

5. Evoke Pharma. FDA Approves Evoke’s GIMOTI™. June 19, 2020. Accessed August 27, 2025. https://investor.evokepharma.com/news-releases/news-release-details/fda-approves-evokes-gimotitm

6. Kanto WP. An FDA Warning About Metoclopramide. NEJM Journal Watch. March 18, 2009. Accessed August 27, 2025. https://www.jwatch.org/pa200903180000001/2009/03/18/fda-warning-about-metoclopramide

7. Johns Hopkins Medicine. Gastroparesis Treatment. Accessed August 27, 2025. https://www.hopkinsmedicine.org/health/conditions-and-diseases/gastroparesis/gastroparesis-treatment

8. Brooks A. FDA Issues CRL to Vanda Pharmaceuticals’ Tradipitant for Gastroparesis Symptoms. HCPLive. September 19, 2024. Accessed August 27, 2025.