RARE DISEASE
Idiopathic gastroparesis
Idiopathic gastroparesis
Idiopathic gastroparesis
Drug discovery
0
drugs
With orphan designations
Overview
Idiopathic gastroparesis is a chronic gastric motility disorder characterized by delayed stomach emptying without mechanical obstruction, presenting with nausea, vomiting, postprandial fullness, and abdominal pain [6][15]. Diagnosis requires exclusion of secondary causes (e.g., diabetes, surgery) and confirmation via gastric emptying studies [1][18]. It is the most common gastroparesis subtype, though its pathophysiology remains unclear, often overlapping with functional dyspepsia [6][15].
Burden
High healthcare utilization: Average inpatient costs reach $7,000/month, with frequent ED visits/hospitalizations [2][4][14].
Significantly impacts quality of life due to chronic symptoms, malnutrition risk, and comorbid anxiety/depression [11][15][19]. Mortality rates exceed the general population, often linked to complications like malnutrition [14][15].
*Domperidone access restricted in the US via FDA IND protocol [3][18].
Therapies
First-line: Dietary modifications (small, low-fiber/low-fat meals), antiemetics (ondansetron), and prokinetics (metoclopramide, domperidone*) [1][3][18].
Refractory cases: Consider endoscopic interventions (G-POEM) or gastric electrical stimulation [1][3][12]. Avoid opioids and GLP-1 agonists due to motility impairment [1][16].
Categories: rare gastroenterological diseases
Research Papers
785 drug discovery papers about Idiopathic gastroparesis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
785 drug discovery papers about Idiopathic gastroparesis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-05 | Gastroparesis: A Comprehensive Overview of Pathophysiology, Etiology, Diagnosis, and Multidisciplinary Management
Gastroparesis is a chronic, often debilitating disorder of gastric motility defined by objectively delayed gastric emptying in the absence of mechanical obstruction, with symptoms persisting for at least three months. The clinical presentation—dominated by nausea, vomiting, early satiety, postprandial fullness, bloating, and abdominal pain—correlates only modestly with the degree of emptying delay, posing a persistent diagnostic challenge. The underlying pathophysiology is multifactorial, involving dysfunction at multiple levels: autonomic (vagal and sympathetic) dysregulation, impaired antral contractility, pyloric sphincter abnormalities, loss of interstitial cells of Cajal (the gastric pacemakers), and, increasingly recognized, localized inflammatory infiltration of the myenteric plexus. The most common etiologies are idiopathic (approximately 50% of cases), followed by diabetic, postsurgical, and postinfectious causes. Diabetic gastroparesis, more frequent and severe in type 1 diabetes, is closely linked to poor glycemic control and other autonomic neuropathies, while postsurgical gastroparesis often results from iatrogenic vagal injury. The incidence has risen markedly over recent decades, paralleling increases in diabetes, obesity, and use of causative medications such as GLP-1 agonists and opioids. Diagnostic evaluation centers on gastric emptying scintigraphy, the gold standard, with the wireless motility capsule and gastric emptying breath test serving as useful alternatives. Treatment requires a holistic, interprofessional approach: dietary modification (small, low-fat, low-fiber meals) forms the foundation; pharmacotherapy is limited, with metoclopramide as the only FDA-approved prokinetic, though its use is constrained by a black box warning for tardive dyskinesia. Off-label agents including domperidone, erythromycin, and antiemetics provide symptomatic relief. For refractory cases, gastric electrical stimulation offers a surgical option, particularly in diabetic patients. Prognosis varies widely by etiology: postinfectious gastroparesis often resolves within 12 months, while diabetic and idiopathic forms tend to be chronic, with significant impacts on quality of life, nutritional status, and healthcare utilization. An interprofessional team—integrating gastroenterologists, dietitians, pharmacists, diabetes educators, and mental health professionals—is essential to optimize outcomes in this challenging patient population.
2026-06-01 | Achieving Symptom Control in the Treatment of Gastroparesis: From Pills to Pacing
Abstract Background Gastroparesis is a chronic disorder of the stomach characterized by delayed emptying without mechanical obstruction. Affected patients experience nausea, vomiting, and a feeling of fullness. Achieving sufficient symptom control remains challenging. Aims The aim of this retrospective study was to analyse the use and effectiveness of current treatment options employed in a step-up approach: 1.Dietary changes, 2.pharmacological treatment (prokinetic drugs including domperidone and prucalopride, and laxatives), 3.pyloric interventions (endoscopic balloon dilation, gastric per-oral endoscopic myotomy (G-POEM), laparoscopic surgical pyloromyotomy), and 4.gastric electrical stimulation (GES, EnterraTM). Methods All patients treated for gastroparesis at a tertiary hospital by a dedicated team between 01/2025 and 01/2026 were included. Diagnosis was confirmed by gastric emptying scintigraphy. Exclusion criteria were previous upper gastrointestinal tract surgery, concomitant hiatal hernia or gastroesophageal reflux disease (GERD), and intestinal failure. Main outcome was sufficient symptom control at the latest available follow-up defined as improved or contained symptoms without need for treatment escalation. Results Fifty patients were included. Median age was 39 years (IQR 25-57), 66% were female. Reasons for gastroparesis was idiopathic in 80%, diabetes in 8%, and rheumatologic or neurologic disease in 12%. Most frequent symptoms were feeling of fullness (82%) and nausea (74%). Sufficient symptom control following conservative treatment was achieved in 13 patients (26%). Eighteen patients (36%) underwent at least one pyloric intervention [G-POEM (n=5), dilatation (n=10), laparoscopic pyloromyotomy (n=5)], with five patients (10%) achieving sufficient symptom control. Fifteen patients (30%) received a GES device, of which two-thirds (n=10) achieved sufficient symptom control. Twenty patients (40%) had at least two interventions during their treatment course. Conclusion Adequate symptom control often requires escalation beyond conservative treatment. Many patients need multiple interventions, emphasizing the chronic nature of gastroparesis. These findings highlight the importance of an individualized, multimodal treatment approach and the need to further investigate predictors of treatment response.
2026-04-03 | Efficacy and Safety of Domperidone for Patients With Symptoms of Gastroparesis; Long-Term Results.
Domperidone is used to treat refractory symptoms of gastroparesis. There is awareness about the risks and benefits of using domperidone; however, studies have primarily been short-term. To review treatment results with domperidone with focus on long-term efficacy and side effects. Patients with gastroparesis symptoms who entered our FDA IND, IRB-approved domperidone protocol between 2005 and 2025 were treated with oral domperidone 10 mg 3-4 times daily and followed every 2 months for the first year, then every 6 months. Patients completed Patient Assessment of Upper GI Symptoms (PAGI-SYM) and Clinical Patient Grading Assessment Scale (CPGAS; +3 = great deal better, 0 = no change). 827 patients (64% idiopathic, 22% diabetic, 6% postsurgical, 5% atypical) participated; delayed gastric emptying in 86%, normal in 13%, and rapid in 1%. 298 patients have continued domperidone for 7.6 ± 6.4 years with a dose of 36 ± 20 mg per day. The CPGAS benefit score averaged 2.3 ± 0.9 (~"moderately better"). There were improvements in symptoms, particularly nausea, postprandial fullness, and loss of appetite. 529 patients stopped domperidone treatment; lack of efficacy (114 patients), side effects (100), switching to another treatment (42), cost (26), and the remainder lost to follow up. Most common side effects for stopping DOM were palpitations (20 patients), prolonged EKG QTc (13), chest pain (11), diarrhea (10), headache (9), dizziness (8), and lactation (8). In this study of patients treated with long term domperidone for symptoms of gastroparesis, 298 of 827 (36%) patients continued treatment for a mean of 7.6 years with patients reporting being moderately better. Thus, in select patients, domperidone treatment is an effective long-term treatment for symptoms of gastroparesis, able to be safely administered with careful patient monitoring.
2026-03-11 | Progress in Gastroparesis Management: From Pharmacotherapy to Interventional Treatments.
Gastroparesis is a sensorimotor condition characterized by delayed gastric emptying without any obvious mechanical obstruction. Common symptoms include early satiety, nausea, vomiting, belching, and bloating. The most frequent causes of gastroparesis are diabetes, idiopathic factors, and post-surgical complications. Currently, the only FDA-approved medication for treating gastroparesis is metoclopramide; however, due to its potential side effects, particularly extrapyramidal symptoms, there is increasing interest in safer, more tolerable alternatives, such as prokinetics, antiemetics, and fundic relaxants. Recent advancements in pharmacological agents have demonstrated variable efficacy in improving gastric emptying and gastroparesis-related symptoms, although symptom improvement does not consistently correlate with changes in gastric emptying metrics. In addition to pharmacological treatments, non-pharmacological approaches like gastric peroral endoscopic myotomy (G-POEM) and neuromodulation techniques have demonstrated significant improvements in symptoms and gastric emptying. The current understanding of gastroparesis care is still limited, and the best practices in treatment remain uncertain. Future research should prioritize multicenter trials that involve large patient populations to explore emerging therapies and innovative techniques. In this review, we will discuss the existing standards of care, advancements in novel pharmacological, interventional, and neuromodulatory treatments for gastroparesis, as well as their clinical integration, limitations, and prospects.
2025-10-01 | S1149 A Wrinkle in the Plan: Pyloric Botox May Complicate Eventual G-POEM
Introduction: Pyloric directed therapies including pyloric Botox injection or gastric peroral endoscopic myotomy (G-POEM) can benefit some patients with refractory gastroparesis. With the increase in use of G-POEM among these patients, we aim to evaluate how prior pyloric Botox injections may impact G-POEM outcomes. Methods: We conducted a retrospective review of patients who underwent G-POEM at our institution between April 2019 and 2025. We collected demographic information and details of prior treatments including the number of prior Botox injections. G-POEM procedural details collected included total procedure time, time from incision start to closing end, and time spent on tunneling, myotomy, and closing. Patients were grouped based on how many prior Botox injections they had received. Welch’s t-tests were performed to evaluate differences in procedural times between groups. Results: A total of 50 patients underwent G-POEM during our study period. The majority (N = 42, 84.0%) of patients had prior pyloric Botox injections. Of these, most (73.8%) were women and had idiopathic gastroparesis (64.0%). All procedures were technically successful and there were no complications. Patients were divided into 2 groups, those with 0-1 prior pyloric injections and those with at least 2 prior injections. Patients with 2+ prior injections had a significantly longer average total procedure time compared to those with 0-1 (67.94 vs 56.11 minutes respectively, P = 0.040). A total of 35 patients had full procedural timing details available. When comparing groups in this subset, patients with 2+ prior injections had significantly longer procedure components compared to those that had 0-1 prior injections, including longer average closing time (16.16 vs 10.43 minutes, P = 0.01) and longer average time from incision start to closure end (52.60 vs 36.86 minutes, P = 0.001). There was a trend towards significance with the 2+ prior injection group having a longer average tunneling time compared to those with 0-1 injections (21.28 vs 16.14 minutes, P = 0.07). Conclusion: Our results identified a new consideration in the risk-benefit evaluation of pyloric Botox injections in patients with refractory gastroparesis. Among patients undergoing G-POEM, having repeated Botox injections to the pylorus is associated with longer procedural times. We hypothesize that this may be due to increased fibrosis from repeated instrumentation, which then complicates certain aspects of the procedure and overall procedure time.
2026-06-05 | Gastroparesis: A Comprehensive Overview of Pathophysiology, Etiology, Diagnosis, and Multidisciplinary Management
Gastroparesis is a chronic, often debilitating disorder of gastric motility defined by objectively delayed gastric emptying in the absence of mechanical obstruction, with symptoms persisting for at least three months. The clinical presentation—dominated by nausea, vomiting, early satiety, postprandial fullness, bloating, and abdominal pain—correlates only modestly with the degree of emptying delay, posing a persistent diagnostic challenge. The underlying pathophysiology is multifactorial, involving dysfunction at multiple levels: autonomic (vagal and sympathetic) dysregulation, impaired antral contractility, pyloric sphincter abnormalities, loss of interstitial cells of Cajal (the gastric pacemakers), and, increasingly recognized, localized inflammatory infiltration of the myenteric plexus. The most common etiologies are idiopathic (approximately 50% of cases), followed by diabetic, postsurgical, and postinfectious causes. Diabetic gastroparesis, more frequent and severe in type 1 diabetes, is closely linked to poor glycemic control and other autonomic neuropathies, while postsurgical gastroparesis often results from iatrogenic vagal injury. The incidence has risen markedly over recent decades, paralleling increases in diabetes, obesity, and use of causative medications such as GLP-1 agonists and opioids. Diagnostic evaluation centers on gastric emptying scintigraphy, the gold standard, with the wireless motility capsule and gastric emptying breath test serving as useful alternatives. Treatment requires a holistic, interprofessional approach: dietary modification (small, low-fat, low-fiber meals) forms the foundation; pharmacotherapy is limited, with metoclopramide as the only FDA-approved prokinetic, though its use is constrained by a black box warning for tardive dyskinesia. Off-label agents including domperidone, erythromycin, and antiemetics provide symptomatic relief. For refractory cases, gastric electrical stimulation offers a surgical option, particularly in diabetic patients. Prognosis varies widely by etiology: postinfectious gastroparesis often resolves within 12 months, while diabetic and idiopathic forms tend to be chronic, with significant impacts on quality of life, nutritional status, and healthcare utilization. An interprofessional team—integrating gastroenterologists, dietitians, pharmacists, diabetes educators, and mental health professionals—is essential to optimize outcomes in this challenging patient population.
2026-06-01 | Achieving Symptom Control in the Treatment of Gastroparesis: From Pills to Pacing
Abstract Background Gastroparesis is a chronic disorder of the stomach characterized by delayed emptying without mechanical obstruction. Affected patients experience nausea, vomiting, and a feeling of fullness. Achieving sufficient symptom control remains challenging. Aims The aim of this retrospective study was to analyse the use and effectiveness of current treatment options employed in a step-up approach: 1.Dietary changes, 2.pharmacological treatment (prokinetic drugs including domperidone and prucalopride, and laxatives), 3.pyloric interventions (endoscopic balloon dilation, gastric per-oral endoscopic myotomy (G-POEM), laparoscopic surgical pyloromyotomy), and 4.gastric electrical stimulation (GES, EnterraTM). Methods All patients treated for gastroparesis at a tertiary hospital by a dedicated team between 01/2025 and 01/2026 were included. Diagnosis was confirmed by gastric emptying scintigraphy. Exclusion criteria were previous upper gastrointestinal tract surgery, concomitant hiatal hernia or gastroesophageal reflux disease (GERD), and intestinal failure. Main outcome was sufficient symptom control at the latest available follow-up defined as improved or contained symptoms without need for treatment escalation. Results Fifty patients were included. Median age was 39 years (IQR 25-57), 66% were female. Reasons for gastroparesis was idiopathic in 80%, diabetes in 8%, and rheumatologic or neurologic disease in 12%. Most frequent symptoms were feeling of fullness (82%) and nausea (74%). Sufficient symptom control following conservative treatment was achieved in 13 patients (26%). Eighteen patients (36%) underwent at least one pyloric intervention [G-POEM (n=5), dilatation (n=10), laparoscopic pyloromyotomy (n=5)], with five patients (10%) achieving sufficient symptom control. Fifteen patients (30%) received a GES device, of which two-thirds (n=10) achieved sufficient symptom control. Twenty patients (40%) had at least two interventions during their treatment course. Conclusion Adequate symptom control often requires escalation beyond conservative treatment. Many patients need multiple interventions, emphasizing the chronic nature of gastroparesis. These findings highlight the importance of an individualized, multimodal treatment approach and the need to further investigate predictors of treatment response.
2026-04-03 | Efficacy and Safety of Domperidone for Patients With Symptoms of Gastroparesis; Long-Term Results.
Domperidone is used to treat refractory symptoms of gastroparesis. There is awareness about the risks and benefits of using domperidone; however, studies have primarily been short-term. To review treatment results with domperidone with focus on long-term efficacy and side effects. Patients with gastroparesis symptoms who entered our FDA IND, IRB-approved domperidone protocol between 2005 and 2025 were treated with oral domperidone 10 mg 3-4 times daily and followed every 2 months for the first year, then every 6 months. Patients completed Patient Assessment of Upper GI Symptoms (PAGI-SYM) and Clinical Patient Grading Assessment Scale (CPGAS; +3 = great deal better, 0 = no change). 827 patients (64% idiopathic, 22% diabetic, 6% postsurgical, 5% atypical) participated; delayed gastric emptying in 86%, normal in 13%, and rapid in 1%. 298 patients have continued domperidone for 7.6 ± 6.4 years with a dose of 36 ± 20 mg per day. The CPGAS benefit score averaged 2.3 ± 0.9 (~"moderately better"). There were improvements in symptoms, particularly nausea, postprandial fullness, and loss of appetite. 529 patients stopped domperidone treatment; lack of efficacy (114 patients), side effects (100), switching to another treatment (42), cost (26), and the remainder lost to follow up. Most common side effects for stopping DOM were palpitations (20 patients), prolonged EKG QTc (13), chest pain (11), diarrhea (10), headache (9), dizziness (8), and lactation (8). In this study of patients treated with long term domperidone for symptoms of gastroparesis, 298 of 827 (36%) patients continued treatment for a mean of 7.6 years with patients reporting being moderately better. Thus, in select patients, domperidone treatment is an effective long-term treatment for symptoms of gastroparesis, able to be safely administered with careful patient monitoring.
2026-03-11 | Progress in Gastroparesis Management: From Pharmacotherapy to Interventional Treatments.
Gastroparesis is a sensorimotor condition characterized by delayed gastric emptying without any obvious mechanical obstruction. Common symptoms include early satiety, nausea, vomiting, belching, and bloating. The most frequent causes of gastroparesis are diabetes, idiopathic factors, and post-surgical complications. Currently, the only FDA-approved medication for treating gastroparesis is metoclopramide; however, due to its potential side effects, particularly extrapyramidal symptoms, there is increasing interest in safer, more tolerable alternatives, such as prokinetics, antiemetics, and fundic relaxants. Recent advancements in pharmacological agents have demonstrated variable efficacy in improving gastric emptying and gastroparesis-related symptoms, although symptom improvement does not consistently correlate with changes in gastric emptying metrics. In addition to pharmacological treatments, non-pharmacological approaches like gastric peroral endoscopic myotomy (G-POEM) and neuromodulation techniques have demonstrated significant improvements in symptoms and gastric emptying. The current understanding of gastroparesis care is still limited, and the best practices in treatment remain uncertain. Future research should prioritize multicenter trials that involve large patient populations to explore emerging therapies and innovative techniques. In this review, we will discuss the existing standards of care, advancements in novel pharmacological, interventional, and neuromodulatory treatments for gastroparesis, as well as their clinical integration, limitations, and prospects.
2025-10-01 | S1149 A Wrinkle in the Plan: Pyloric Botox May Complicate Eventual G-POEM
Introduction: Pyloric directed therapies including pyloric Botox injection or gastric peroral endoscopic myotomy (G-POEM) can benefit some patients with refractory gastroparesis. With the increase in use of G-POEM among these patients, we aim to evaluate how prior pyloric Botox injections may impact G-POEM outcomes. Methods: We conducted a retrospective review of patients who underwent G-POEM at our institution between April 2019 and 2025. We collected demographic information and details of prior treatments including the number of prior Botox injections. G-POEM procedural details collected included total procedure time, time from incision start to closing end, and time spent on tunneling, myotomy, and closing. Patients were grouped based on how many prior Botox injections they had received. Welch’s t-tests were performed to evaluate differences in procedural times between groups. Results: A total of 50 patients underwent G-POEM during our study period. The majority (N = 42, 84.0%) of patients had prior pyloric Botox injections. Of these, most (73.8%) were women and had idiopathic gastroparesis (64.0%). All procedures were technically successful and there were no complications. Patients were divided into 2 groups, those with 0-1 prior pyloric injections and those with at least 2 prior injections. Patients with 2+ prior injections had a significantly longer average total procedure time compared to those with 0-1 (67.94 vs 56.11 minutes respectively, P = 0.040). A total of 35 patients had full procedural timing details available. When comparing groups in this subset, patients with 2+ prior injections had significantly longer procedure components compared to those that had 0-1 prior injections, including longer average closing time (16.16 vs 10.43 minutes, P = 0.01) and longer average time from incision start to closure end (52.60 vs 36.86 minutes, P = 0.001). There was a trend towards significance with the 2+ prior injection group having a longer average tunneling time compared to those with 0-1 injections (21.28 vs 16.14 minutes, P = 0.07). Conclusion: Our results identified a new consideration in the risk-benefit evaluation of pyloric Botox injections in patients with refractory gastroparesis. Among patients undergoing G-POEM, having repeated Botox injections to the pylorus is associated with longer procedural times. We hypothesize that this may be due to increased fibrosis from repeated instrumentation, which then complicates certain aspects of the procedure and overall procedure time.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.