Dear editor,

The increasing prevalence of obesity and type 2 diabetes has led to a surge in the use of long-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs). While these medications are approved for the treatment of type 2 diabetes and obesity, their use has important implications for intensivists, as critically ill patients admitted to the intensive care unit (ICU) may have been receiving these medications prior to admission.

Given the prolonged half-lives of long-acting GLP-1 RAs, such as semaglutide (half-life of approximately 7 days) [1], their effects may persist throughout a patient's ICU stay, even if the medication is discontinued upon admission. This prolonged action can have significant implications for the management of these patients, particularly in terms of gastric emptying, enteral nutrition tolerance, and glycemic control.

Recent literature has highlighted the potential impact of GLP-1 RAs on gastric emptying in patients under anesthesia. Sen and colleagues reported that patients who were taking GLP1 RAs prior to surgery had larger cross sectional areas of the gastric antrum than those who weren’t taking GLP1 RAs [2]. Whether this has any impact on the risk of aspiration is unknown [3]. It is important that intensivists understand that short-acting GLP-1 RAs have a greater impact on gastric emptying than long acting GLP 1 RAs [4]. While GLP-1 has a marked glucose lowering effect in the critically ill [5], which is mediated, at least in part by slowing gastric emptying, this occurs when gastric emptying is relatively normal, but not when it is delayed [6]. Prokinetic drugs, such as erythromycin, counteract the slowing of gastric emptying that occurs with GLP-1 [7].

Furthermore, the impact of long-acting GLP-1 RAs on glycemic control in critically ill patients remains poorly understood. GLP-1 RAs attenuate stress-induced hyperglycemia [8], with a reduced risk of hypoglycemia when compared to insulin administration [9], but the effects in patients with renal failure are unknown [10].

As the use of long-acting GLP-1 RAs continues to expand, intensivists must be prepared to manage the unique challenges these medications may pose in the critical care setting. We call for further research to better understand the impact of GLP-1 RAs on critical care outcomes. Additionally, we urge the development of evidence-based guidelines to assist clinicians in managing patients receiving these medications in the ICU, with a focus on monitoring strategies, dose adjustments, and the potential need for alternative management approaches.

In conclusion, the increasing use of long-acting GLP-1 RAs prior to ICU presents unique challenges for intensivists managing critically ill patients. By addressing the current knowledge gaps and developing evidence-based guidelines, we can optimize the care of these patients and improve their outcomes in the ICU.

Not applicable.

GLP-1 RAs:

Glucagon-like peptide-1 receptor agonists

ICU:

Intensive care unit

1. Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide. Front Endocrinol. 2019;10:155.

   Article Google Scholar

2. Sen S, Potnuru PP, Hernandez N, Goehl C, Praestholm C, Sridhar S, Nwokolo OO. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg. 2024.

3. van Zuylen ML, Siegelaar SE, Plummer MP, Deane AM, Hermanides J, Hulst AH. Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration. Br J Anaesth. 2024;132(4):644–8.

   Article PubMed Google Scholar

4. Umapathysivam MM, Lee MY, Jones KL, Annink CE, Cousins CE, Trahair LG, et al. Comparative effects of prolonged and intermittent stimulation of the glucagon-like peptide 1 receptor on gastric emptying and glycemia. Diabetes. 2014;63(2):785–90.

   Article CAS PubMed PubMed Central Google Scholar

5. Deane AM, Chapman MJ, Fraser RJ, Burgstad CM, Besanko LK, Horowitz M. The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study. Crit Care. 2009;13(3):R67.

   Article PubMed PubMed Central Google Scholar

6. Deane AM, Chapman MJ, Fraser RJ, Summers MJ, Zaknic AV, Storey JP, et al. Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: relationship to glycemia. Crit Care Med. 2010;38(5):1261–9.

   Article CAS PubMed Google Scholar

7. Meier JJ, Kemmeries G, Holst JJ, Nauck MA. Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like peptide 1 and unmasks its insulinotropic effect in healthy subjects. Diabetes. 2005;54(7):2212–8.

   Article CAS PubMed Google Scholar

8. Plummer MP, Chapman MJ, Horowitz M, Deane AM. Incretins and the intensivist: what are they and what does an intensivist need to know about them? Crit Care (London, England). 2014;18(2):205.

   Article Google Scholar

9. Plummer MP, Hermanides J, Deane AM. Incretin physiology and pharmacology in the intensive care unit. Crit Care Clin. 2019;35(2):341–55.

   Article PubMed Google Scholar

10. Mustafa OG, Whyte MB. The use of GLP-1 receptor agonists in hospitalised patients: an untapped potential. Diabetes Metab Res Rev. 2019;35(8): e3191.

    Article PubMed PubMed Central Google Scholar

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The work was supported by grants from the China National Key Research and Development Program (No. 2020AAA0105005), National Natural Science Foundation of China (81901998), Chengdu Science and Technology Bureau (2021-YF05-00071-SN), Key Research and Development Project of Science and Technology Department of Sichuan Province (2021YFS0003), and 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC18006).

Authors and Affiliations

1. Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China

   Luping Wang, Hao Yang, Xiaoxiao Xia, Bo Wang & Qin Wu

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Contributions

LW, YH and QW conceived the study. LW, XX and QW wrote the manuscript. HY, BW and QW substantively revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Qin Wu.

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Wang, L., Yang, H., Xia, X. et al. Potential implications of long-acting GLP-1 receptor agonists for critically ill. Crit Care 28, 159 (2024). https://doi.org/10.1186/s13054-024-04945-9

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• Received: 03 April 2024

• Accepted: 08 May 2024

• Published: 13 May 2024

• DOI: https://doi.org/10.1186/s13054-024-04945-9

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