Effects of liraglutide on gastrointestinal functions and weight in obesity: A randomized clinical and pharmacogenomic trial
Open accessAbstract
Objective: This study aimed to determine the effects of a long‐acting glucagon‐like peptide‐1 (GLP‐1) receptor agonist, liraglutide, and placebo subcutaneously over 16 weeks on weight and gastric functions and to evaluate associations of single‐nucleotide polymorphisms in GLP1R (rs6923761) and TCF7L2 (rs7903146) with effects of liraglutide. Methods: The study conducted a randomized, parallel‐group, placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg subcutaneously daily in 136 otherwise healthy adults with obesity. Weight, gastric emptying of solids (GES), gastric volumes, satiation, and body composition measured at baseline and after treatment were compared in two treatment groups using analysis of covariance. Results: Liraglutide ( n = 59) and placebo ( n = 65) groups completed treatment. Relative to placebo, liraglutide increased weight loss at 5 and 16 weeks (both p < 0.05), slowed time to half GES (T 1/2 ) at 5 and 16 weeks (both p < 0.001), and increased fasting gastric volume ( p = 0.01) and satiation ( p < 0.01) at 16 weeks. GES T 1/2 was positively correlated with weight loss on liraglutide (both p < 0.001). After 16 weeks of liraglutide, GLP1R rs6923761 (AG/AA vs. GG) was associated with reduced percent body fat ( p = 0.062), and TCF7L2 rs7903146 (CC vs. CT/TT) was associated with lower body weight ( p = 0.015). Conclusions: Liraglutide, 3 mg, induces weight loss with delay in GES T 1/2 and reduces calorie intake. Slowing GES and variations in GLP1R and TCF7L2 are associated with liraglutide effects in obesity.
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The time course of tachyphylaxis of GE delay may be longer with retatrutide compared with previously studied incretins.
“The time course of tachyphylaxis of GE delay may be longer with retatrutide compared with previously studied incretins.12,13”
From The novel <scp>GIP</scp> , <scp>GLP</scp> ‐1 and glucagon receptor agonist retatrutide delays gastric emptying (2023) · cites this paper as [13]
The Discussion (page not provided) reports that liraglutide’s gastric-emptying effect was smaller at 16 weeks than at 5 weeks, consistent with tachyphylaxis. The paper does not study retatrutide or compare its time course with that of liraglutide or other incretins, so it supports only the previously studied-incretin side of the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSimilar reports of tachyphylaxis of GE delay have been reported for liraglutide based on assessments at 16 weeks versus an earlier time point of 5 weeks.
“Similar reports of tachyphylaxis of GE delay have been reported for liraglutide based on assessments at 16 weeks versus an earlier time point of 5 weeks.13”
From The novel <scp>GIP</scp> , <scp>GLP</scp> ‐1 and glucagon receptor agonist retatrutide delays gastric emptying (2023) · cites this paper as [13]
Glucagon-like peptide-1 receptor agonists slow the rate of post-prandial gastric emptying.
“This group of drugs slows the rate of post‐prandial gastric emptying [2, 3, 4]”
From Association between glucagon-like peptide-1 receptor agonist use and peri-operative pulmonary aspiration: a systematic review and meta-analysis (2025) · cites this paper as [4]
GLP-1 receptor agonists induce weight loss primarily by appetite inhibition and slowed gastric emptying, and have been shown to improve eating behaviours.
“GLP-1 receptor agonists induce weight loss primarily by appetite inhibition5,6,36 and slowed gastric emptying,37 and have been shown to improve eating behaviours, i.e., reduce uncontrolled and emotional eating and improve cognitive restraint.6,38”
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- Authors
- Maselli, D., Atieh, J., Clark, M. M., Eckert, D., Taylor, A., Carlson, P., Burton, D. D., Busciglio, I., Harmsen, W. S., Vella, A., Acosta, A., & Camilleri, M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Camilleri, Michael
- ORCID
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2022-07-27
- Volume
- 30
- Issue
- 8
- Pages
- 1608-1620
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC9335902
- OpenAlex
- W4288034125
- Semantic Scholar
- 077d102ebcd2ecf9afb62035db8aeda3322c6682
- Cited by
- 136
- References
- 45
- Citations by year
- 2026: 34 · 2025: 37 · 2024: 40 · 2023: 20 · 2022: 3
- FWCI
- 14.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Center for Clinical and Translational Science, Mayo Clinic (UL1‐TR000135)
- National Institutes of Health (R01‐DK67071)
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- liraglutide, GLP-1 receptor agonists, gastric emptying, gastric volume, satiation, weight loss, pharmacogenomics, single nucleotide polymorphisms, body composition
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Adult, Double-Blind Method, Humans, Hypoglycemic Agents, Obesity, Pharmacogenetics, Weight Loss, Glucagon-Like Peptide 1
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