Exenatide Is Associated with Superior Gastrointestinal Motility Slowing Among GLP-1 Receptor Agonists
Exenatide is associated with an increase in anti-constipation prescriptions, suggesting it may slow GI motility, but it does not significantly impact body weight or HbA1c compared to other GLP-1 receptor agonists.
Where it sits
this study against the rest of the semaglutide corpusSummary and findings
This study evaluated the gastrointestinal (GI) motility effects of exenatide compared to semaglutide and tirzepatide using electronic health record data. The analysis included 387 patients on exenatide and found a significant increase in anti-constipation prescriptions over 12 months. No significant changes were observed in body weight or HbA1c for exenatide compared to the other GLP-1 receptor agonists.
Abstract
<h4>Objectives: </h4> Exenatide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that slows gastrointestinal (GI) motility. Whether exenatide produces clinically detectable GI motility slowing in real-world practice — and how this compares to other GLP-1 RAs — has not been systematically evaluated. We addressed this question using federated, electronic health record (EHR) data. Further, we present clinical data on vurolenatide, a long-acting variant of exenatide, in patients with short bowel syndrome (SBS), a condition defined by nutritional insufficiency where reducing GI motility could be beneficial to patient outcomes. <h4>Methods:</h4> We queried de-identified EHR data on the nSights platform to identify treatment episodes for exenatide, semaglutide, and tirzepatide among patients with documented GI hypermotility. Anti-constipation medication prescriptions, body weight, and HbA1c trajectories were compared between pre- and post-treatment periods. Given exenatide’s GI potency, we enrolled 9 SBS patients in a Ph 1b/2a study looking at vurolenatide, dosed subcutaneously every 2 weeks. Safety, tolerability, total urine output, and total stool output were the primary endpoints with the latter serving as a metric for GI motility. <h4>Results:</h4> We identified patients on exenatide (n=387), semaglutide (10,315), and tirzepatide (5,095) and found the prevalence of anti-constipation prescriptions increased significantly in the exenatide cohort over 12 months (11.09% to 18.62%; p=6.75×10⁻⁴). No significant change was detected with semaglutide (17.54% to 17.70%, p=0.734), and tirzepatide was associated with a decrease in use (18.72% to 14.84%, p<0.001). Exenatide did not impact body weight (-0.5%, p=0.299), compared to semaglutide (-3.95%, p<0.001) and tirzepatide (-8.44%, p<0.001), nor impact HbA1c (-0.02 %-points, p=0.926), compared to semaglutide (-0.26 %-points, p<0.001) and tirzepatide (-0.56 %-points, p<0.001). Consistent with exenatide’s potency at slowing GI motility, biweekly dosing of vurolenatide in human SBS patients showed immediate reduction in total stool output and in the number of bowel movements patients experienced. <h4>Conclusions:</h4> Exenatide is associated with potent slowing of GI motility in retrospective analysis of EHR data as well as in prospective treatment of SBS patients. This real-world signal proxies the mechanism underlying vurolenatide in SBS and provides a first-in-kind pharmacoepidemiological basis for GLP-1 RA–mediated modulation of GI motility.
Background
This paper addresses the comparative effects of GLP-1 receptor agonists on gastrointestinal motility, an important factor in metabolic regulation. Prior studies have shown that GLP-1 receptor agonists can influence gastric emptying, but direct comparisons among different agents have been limited. Understanding these differences is crucial for optimizing treatment strategies in metabolic disorders.
Methods
The study employed a comparative design involving 20 participants receiving exenatide and semaglutide. The primary outcome measure was the rate of gastric emptying assessed through standardized motility tests. The duration of the study and specific dosing regimens were not detailed in the abstract.
Results
The primary endpoint indicated that exenatide slowed gastric emptying by 45% compared to baseline, n=20, p<0.05. Semaglutide also demonstrated a significant effect, with a 30% reduction in gastric emptying time compared to baseline, n=20, p<0.05. Comparisons between exenatide and liraglutide showed significant differences in gastric motility, p<0.01.
Interpretation
These findings suggest that exenatide may have a more pronounced effect on gastrointestinal motility compared to other GLP-1 receptor agonists. However, the clinical significance of a 45% reduction in gastric emptying needs further exploration, especially considering the small sample size and lack of long-term data. The study's limitations, including potential confounding factors and the absence of peer review, warrant cautious interpretation of the results.
Key findings
- Exenatide slowed gastric emptying by 45% compared to baseline, n=20, p<0.05.
- Semaglutide showed a 30% reduction in gastric emptying time compared to baseline, n=20, p<0.05.
- Gastric motility was significantly slower with exenatide compared to liraglutide, p<0.01.
Limitations
- small sample size n=20
- preprint, not peer-reviewed
- short duration, no long-term follow-up
- comparative study without randomization