Diabetic gastroparesis: An overview of pathogenesis, clinical presentation and novel therapies, with a focus on ghrelin receptor agonists
Abstract
Diabetic gastroparesis is defined as delayed gastric emptying without mechanical obstruction in the setting of diabetes. Symptoms range from mild bloating to severe vomiting episodes and can result in frequent hospitalizations and poor quality of life. It is suspected that diabetic gastroparesis is underdiagnosed due to its similar presentation to other conditions such as gastroesophageal reflux disease. The pathogenesis of diabetic gastroparesis remains unclear, but proposed mechanisms include vagal dysfunction, hyperglycemia, interstitial cells of Cajal network disturbances, loss of neural nitric oxide synthase expression in the myenteric plexus, and oxidative stress. Current management for diabetic gastroparesis focuses on dietary and lifestyle changes as well as improved glycemic control. Limited options for medical therapies are available that include prokinetic and antiemetic medications. Metoclopramide is the only FDA-approved medication for the treatment of gastroparesis. Metoclopramide improves symptoms of gastroparesis although extended treatment presents challenges such as decreased efficacy over time and increased risks for adverse events. We summarize the current knowledge of the pathophysiology of diabetic gastroparesis and review current and investigational treatments for diabetes gastroparesis.
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GES presents limitations: protocol variability, limited availability, and radiation exposure.
“Despite its strengths, GES presents limitations: protocols variability, limited availability, and radiation exposure [14, 61, 64].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [64]
Late postprandial hyperglycemia occurs because once nutrients finally reach the absorptive surface of the small intestine, the circulating insulin concentration has declined, leading to a disproportionate and often prolonged glycemic rise.
“late postprandial hyperglycemia: Once nutrients finally reach the absorptive surface of the small intestine, the circulating insulin concentration has declined, leading to a disproportionate and often prolonged glycemic rise [64, 94, 95].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [64]
Early postprandial hypoglycemia occurs because insulin acts before sufficient carbohydrates enter the small intestine; plasma insulin concentrations rise while circulating glucose remains low due to delayed gastric transit.
“early postprandial hypoglycemia: Insulin acts before sufficient carbohydrates enter the small intestine; plasma insulin concentrations rise while circulating glucose remains low due to delayed gastric transit [64, 94, 95].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [64]
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- Authors
- Petri, M., Singh, I., Baker, C., Underkofler, C., & Rasouli, N.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Rasouli, Neda
- Venue
- Journal of Diabetes and its Complications
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 35
- Issue
- 2
- Pages
- 107733
- ISSN
- 0891-6632 (ISSN-L)
- 1056-8727
- OpenAlex
- W3083539914
- Cited by
- 50
- References
- 0
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 12 · 2023: 4 · 2022: 7 · 2021: 2 · 2020: 2
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Diabetes and its Complications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Allergan
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Keywords
- diabetic gastroparesis, delayed gastric emptying, pathogenesis, ghrelin receptor agonist, metoclopramide, prokinetic agents, antiemetics, vagal dysfunction, interstitial cells of Cajal, oxidative stress, nitric oxide synthase, hyperglycemia, gastroesophageal reflux disease, underdiagnosis, investigational therapies
- MeSH terms
- Diabetes Mellitus, Diabetic Neuropathies, Gastric Emptying, Humans, Metoclopramide, Quality of Life, Gastroparesis, Receptors, Ghrelin
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