Effects of Lixisenatide Versus Liraglutide (Short- and Long-Acting GLP-1 Receptor Agonists) on Esophageal and Gastric Function in Patients With Type 2 Diabetes
Abstract
OBJECTIVE: Short-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs) decelerate gastric emptying more than long-acting GLP-1 RAs. Delayed gastric emptying is a risk factor for gastroesophageal reflux disease. We aimed to measure esophageal reflux and function as well as gastric emptying and acid secretion during treatment with short-acting (lixisenatide) and long-acting (liraglutide) GLP-1 RAs. RESEARCH DESIGN AND METHODS: A total of 57 subjects with type 2 diabetes were randomized to a 10-week treatment with lixisenatide or liraglutide. Changes from baseline in the number of reflux episodes during 24-h pH registration in the lower esophagus, lower esophagus sphincter pressure, gastric emptying (13C-sodium octanoate acid breath test), and gastric acid secretion (13C-calcium carbonate breath test) were analyzed. RESULTS: Gastric emptying half-time was delayed by 52 min (Δ 95% CI 16, 88) with lixisenatide (P = 0.0065) and by 25 min (3, 46) with liraglutide (P = 0.025). There was no difference in the number of reflux episodes (mean ± SEM 33.7 ± 4.1 vs. 40.1 ± 5.3 for lixisenatide and liraglutide, respectively, P = 0.17) or the extent of gastroesophageal reflux (DeMeester score) (35.1 ± 6.7 vs. 39.7 ± 7.5, P = 0.61), with similar results for the individual GLP-1 RAs. No significant changes from baseline in other parameters of esophageal motility and lower esophageal sphincter function were observed. Gastric acidity decreased significantly by −20.7% (−40.6, −0.8) (P = 0.042) with the GLP-1 RAs. CONCLUSIONS: Lixisenatide exerted a more pronounced influence on gastric emptying after breakfast than liraglutide. Neither lixisenatide nor liraglutide had significant effects on esophageal reflux or motility. Gastric acid secretion appears to be slightly reduced by GLP-1 RAs.
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Short-acting GLP-1 RAs produce a more pronounced delay in gastric emptying than long-acting agents.
“In general, short-acting agents produce a more pronounced delay in gastric emptying than long-acting agents [3, 15].”
From Delayed gastric emptying induced by glucagon-like peptide-1 receptor agonists and its implications for perioperative risk during anesthesia (2026) · cites this paper as [15]
The principal mechanism of short-acting GLP-1 RAs involves a sustained delay in gastric emptying, which slows glucose absorption and attenuates the postprandial glycemic peak.
“Their principal mechanism involves a sustained delay in gastric emptying, which slows glucose absorption and attenuates the postprandial glycemic peak [15].”
From Delayed gastric emptying induced by glucagon-like peptide-1 receptor agonists and its implications for perioperative risk during anesthesia (2026) · cites this paper as [15]
GLP-1RAs have been shown to reduce gastric acid secretion, with some studies reporting up to a 20% increase in gastric pH.
“GLP-1RAs have been shown to reduce gastric acid secretion, with some studies reporting up to a 20% increase in gastric pH.19”
From GLP-1RA-induced delays in gastrointestinal motility: Predicted effects on coadministered drug absorption by PBPK analysis (2025) · cites this paper as [19]
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- Authors
- Quast, D. R., Schenker, N., Menge, B. A., Nauck, M. A., Kapitza, C., & Meier, J. J.
- Affiliations
- St. Josef-Hospital (DE)
- Profil Institute for Metabolic Research (DE)
- Corresponding author
- Meier, Juris J.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2020-07-09
- Volume
- 43
- Issue
- 9
- Pages
- 2137-2145
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W3041477129
- Cited by
- 64
- References
- 37
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 20 · 2023: 7 · 2022: 9 · 2021: 4
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Keywords
- liraglutide, GLP-1 receptor agonists, type 2 diabetes, gastroesophageal reflux disease, gastric emptying, esophageal motility, lower esophageal sphincter pressure, gastric acid secretion, 24-hour pH monitoring
- MeSH terms
- Glucagon-Like Peptide-2 Receptor, Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Adult, Aged, Diabetes Mellitus, Type 2, Esophagus, Female, Gastric Acid, Gastric Emptying, Gastroesophageal Reflux, Humans, Hypoglycemic Agents, Male, Middle Aged, Peptides
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