Disclaimer: This article is intended solely for informational and educational purposes only. It does not constitute medical advice.
Gastric emptying is variable process, ranging from approximately 1 to 4 kcal/min in healthy adults, with further variability between individuals (Jalleh et al., 2024). This inter-individual variation has taken on renewed clinical importance with the widespread adoption of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) for type 2 diabetes and obesity, since these agents act, in part, by slowing gastric emptying, which can significantly impact perioperative care.
Recent mechanistic work helps explain why some individuals empty more slowly than others at baseline. Sun and colleagues (2026) demonstrated that the gastric half-emptying time (T50) of an oral glucose load correlates directly with the magnitude of the endogenous GLP-1 response to standardized intraduodenal glucose infusion, independent of gastric emptying itself.
Participants with the slowest gastric emptying exhibited significantly greater GLP-1 and insulin responses than those with the fastest emptying, despite comparable C-peptide and GIP responses, suggesting that differences in intestinal “sensitivity” to nutrients—reflected by endogenous GLP-1 secretion—may be an intrinsic determinant of an individual’s baseline gastric emptying rate. This finding suggests that the variation in gastric emptying in patients taking GLP-1s is part of a bidirectional physiological loop.
This baseline heterogeneity appears to modulate the pharmacological response to exogenous GLP-1RAs. Jalleh and colleagues (2025) note that the degree of slowing induced by both short- and long-acting agents is inversely related to baseline gastric emptying rate: individuals who empty rapidly at baseline experience the greatest deceleration, whereas those with already slow emptying show comparatively little further effect.
Superimposed on this is a divergence between drug classes. Short-acting agents such as exenatide twice daily and lixisenatide produce marked, sustained slowing with little evidence of tachyphylaxis, while long-acting agents—liraglutide, once-weekly exenatide, semaglutide, and efpeglenatide—show attenuation of effect over weeks to months, consistent with receptor-level tachyphylaxis, though residual slowing typically persists (Jalleh et al., 2024; Jalleh et al., 2025).
In a cohort of 67 patients treated with liraglutide titrated to 3 mg daily, 57% (39/67) developed clinically significant delay in gastric emptying by 5 weeks. Of these, roughly half normalized by 16 weeks (tachyphylaxis), while the remainder had persistent delay, such that 30% of the original cohort remained affected at study end. Genetic variants in GLP1R and TCF7L2 did not predict which patients would develop delay or subsequently normalize, underscoring that the determinants of individual responses remain poorly defined.
These findings carry direct implications for perioperative and endoscopic risk stratification. Because gastric emptying delay is neither uniform nor reliably predicted by symptoms, genotype, or duration of therapy, blanket withholding periods before procedures are an imperfect safeguard (Jalleh et al., 2024; Jalleh et al., 2025). As the use of GLP-1s continues to expand, clinicians should recognize that slow gastric emptying can present as a spectrum, with variation partially shaped by baseline intestinal physiology, drug pharmacokinetics, and time-dependent tachyphylaxis.
References
- Camilleri, M., Carlson, P., & Dilmaghani, S. (2024). Prevalence and variations in gastric emptying delay in response to GLP-1 receptor agonist, liraglutide. Obesity (Silver Spring), 32(2), 232–233. https://doi.org/10.1002/oby.23941
- Jalleh, R. J., Rayner, C. K., Hausken, T., Jones, K. L., Camilleri, M., & Horowitz, M. (2024). Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. Lancet Gastroenterology & Hepatology, 9(10), 957–964. https://doi.org/10.1016/S2468-1253(24)00188-2
- Jalleh, R. J., Plummer, M. P., Marathe, C. S., Umapathysivam, M. M., Quast, D. R., Rayner, C. K., Jones, K. L., Wu, T., Horowitz, M., & Nauck, M. A. (2025). Clinical consequences of delayed gastric emptying with GLP-1 receptor agonists and tirzepatide. Journal of Clinical Endocrinology & Metabolism, 110(1), 1–15. https://doi.org/10.1210/clinem/dgae719
- Sun, Y., Xie, C., Borg, M. J., Huang, W., Bound, M., Grivell, J., Jones, K. L., Horowitz, M., Wu, T., & Rayner, C. K. (2026). Inter-individual variation in gastric emptying is related to GLP-1 response to intraduodenal glucose exposure in health. Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgag273
