Gastroparesis, a complex motility disorder, poses significant challenges for patients and healthcare providers alike. Characterized by delayed gastric emptying, this condition often leads to misdiagnosis and a lack of effective treatment options. As a result, both patients and clinicians are urgently seeking better solutions.
According to Brian Lacy, MD, PhD, of the Mayo Clinic, the field of gastroparesis can be described with three key terms: challenging, complicated, and controversial. The intricacies of diagnosis and treatment arise from frequent misdiagnoses and inadequately performed diagnostic tests. In 2022, the American Gastroenterological Association (AGA) released clinical guidelines that outlined appropriate diagnostic tests for gastroparesis. Among these, the AGA recommended scintigraphic gastric emptying of a solid meal lasting at least three hours, emphasizing that shorter studies may yield false negative results.
The limitations of current diagnostic methods are highlighted by Douglas Weinstein, MD, who notes that various factors—such as meal size, composition, and patient position—can affect test outcomes. “Even if everything’s done right, sometimes [the test] will still be normal,” he explained. Furthermore, Adeling Hung, MD, pointed out that key tests like gastric emptying scintigraphy are not widely available outside specialized centers, complicating the identification of the primary cause of gastroparesis.
The 2022 AGA guidelines focus on treatments that lack sufficient support, including neuromodulators and ghrelin agonists. While metoclopramide remains the only FDA-approved treatment specifically for gastroparesis, concerns persist. Originally approved in 1979 for diabetic gastroparesis, this dopamine receptor antagonist has a Black Box warning due to potential side effects, including tardive dyskinesia. “Metoclopramide is not a good medicine because it can’t be used long-term,” Weinstein cautioned.
In 2020, Evoke Pharma introduced a nasal spray formulation of metoclopramide, branded as Gimoti, which marked the first new pharmaceutical treatment for gastroparesis in decades. Despite this advancement, the risks associated with metoclopramide remain a significant concern.
For additional treatment options, some physicians use erythromycin, an antibiotic known for its prokinetic effects. Like metoclopramide, however, its efficacy is limited, and it carries its own risks. “The few approved prokinetics have modest efficacy, short durability, and significant side effects,” noted Hung.
Acknowledging the pressing need for new therapies, Vanda Pharmaceuticals sought to introduce a novel treatment, tradipitant, a neurokinin receptor 1 antagonist. Yet, in September 2024, the FDA issued a Complete Response Letter regarding its New Drug Application, indicating that further studies were necessary to align with scientific understanding of gastroparesis.
As a result, metoclopramide remains the only FDA-approved treatment specifically for this condition, raising questions about the future of effective therapies. “Due to the heterogeneity of the disease and its multiple mechanisms, it is hard to find one treatment that can show appropriate efficacy for all patients,” said Hung. She emphasized the need for better classification of patients and the incorporation of patient-reported outcomes in clinical trials.
Another aspect of the gastroparesis treatment landscape that warrants attention is the evolving understanding of the disorder itself. Lacy advocates for a rethinking of gastroparesis, suggesting it may represent a sensory disorder for many patients rather than solely a motility issue. He stated, “If the field is to move ahead, we need to reframe how we think about the underlying physiology of gastroparesis.”
Despite not being included in the 2022 AGA guidelines, advances in neuromodulation and device-based therapies are gaining traction. Techniques such as gastric electrical stimulation and vagal nerve stimulation show promise in managing symptoms like nausea and vomiting for selected patients. Weinstein described a temporary stimulation trial that helps predict which patients might benefit from these interventions.
“While recognizing the benefit of such approaches, there is a need for more standardization in how to integrate the latest procedures and devices with pharmacological therapy,” said Hung. She believes that aligning these treatment modalities could significantly improve patient outcomes.
As the field navigates the complexities of gastroparesis diagnosis and treatment, collaborative efforts will be essential. Redefining disease mechanisms, enhancing trial designs, and integrating innovative therapies may bridge longstanding treatment gaps. While progress has been slow, the growing recognition of gastroparesis’ heterogeneity and a focus on targeted, patient-centered strategies promise a brighter future for patients who have long awaited better solutions.
Editors’ note: Hung and Weinstein report no relevant disclosures. Lacy reports relevant disclosures with several pharmaceutical companies.
