Persistently Elevated Glucagon-Like Peptide-1 Levels among Critically Ill Surgical Patients after Sepsis and Development of Chronic Critical Illness and Dismal Long-Term Outcomes
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BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin secretion, cellular glucose uptake, and has immune-regulatory functions. Glucagon-like peptide-1 is markedly altered after trauma and sepsis, but the implications remain unclear. STUDY DESIGN: We performed an analysis of a prospective, longitudinal cohort study of critically ill surgical patients with sepsis. Patient characteristics and clinical data were collected, as well as peripheral blood sampling for biomarker analysis, out to 28 days after sepsis onset. We prospectively adjudicated sepsis diagnosis, severity, clinical outcomes, and 6-month follow-up. RESULTS: The cohort included 157 septic surgical patients with significant physiologic derangement (Maximum Sequential Organ Failure Assessment [SOFA] score 8, interquartile range [IQR] 4 to 11), a high rate of multiple organ failure (50.3%), and septic shock (24.2%). Despite high disease severity, both early death (<14 days; n = 4, 2.9%) and overall inpatient mortality were low (n = 12, 7.6%). However, post-discharge 6-month mortality was nearly 3-fold higher (19.7%). Both GLP-1 and interleukin [IL]-6 levels were significantly elevated for 21 days (p ≤ 0.01) in patients who developed chronic critical illness (CCI) compared with patients with a rapid recovery. Elevated GLP-1 at 24 hours was a significant independent predictor for the development of CCI after controlling for IL-6 and glucose levels (p = 0.027), and at day 14 for death or severe functional disability at 6 months (WHO/Zubrod score 4-5, p = 0.014). CONCLUSIONS: Elevated GLP-1 within 24 hours of sepsis is a predictor of early death or persistent organ dysfunction. Among early survivors, persistently elevated GLP-1 levels at day 14 are strongly predictive of death or severe functional disability at 6 months. Persistently elevated GLP-1 levels may be a marker of a nonresolving catabolic state that is associated with muscle wasting and dismal outcomes after sepsis and chronic critical illness.
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Circulating GLP-1 levels correlate with severity of critical illnesses, sepsis, end-stage kidney disease, respiratory failure, and intestinal ischemia-reperfusion injury.
“Circulating GLP-1 levels also correlate with severity of critical illnesses (5, 10), sepsis (11), end-stage kidney disease (11), respiratory failure (12), and intestinal ischemia-reperfusion injury (6).”
From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [10]
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Bloch, O., Perl, K., Shimol, A. B., Rotmensh, A., Kagansky, D., Yovel, D. Z., Yehudah, G. B., Cantrell, D., & Rapoport, M. J. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3635 · Cited by 1 · see citing works
Glucagon-Like Peptide-1 Is Prognostic of Mortality in Acute Respiratory Failure
Hansell, C. E., Aneis, H., Kitsios, G. D., Bain, W., Zhao, Y., Suber, T. L., Evankovich, J. W., Sharma, L., Ramakrishnan, S. K., Prendergast, N. T., et al. (2025) · Critical Care Explorations · doi:10.1097/cce.0000000000001247 · Cited by 1 · see citing works
The Evolving Syndrome of Multiple Organ Failure into PICS-CCI
Moore, F. A. (2022) · Hot topics in acute care surgery and trauma · doi:10.1007/978-3-030-92241-2_5
Self-citationThe evolving epidemiology of multiple organ failure
Moore, F. A. (2023) · Current Therapy of Trauma and Surgical Critical Care · doi:10.1016/b978-0-323-69787-3.00125-8
Self-citationIncretins: From Gene Expression to Secretion and Action of GLP-1 and GIP
Lobato, C. B., & Holst, J. J. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-11985-9.00004-4
- Authors
- Brakenridge, S. C., Moore, F. A., Mercier, N. R., Cox, M., Wu, Q., Moldawer, L. L., Mohr, A. M., Efron, P. A., & Smith, S. R.
- Affiliations
- University of Florida Health (US)
- University of Arkansas for Medical Sciences (US)
- Venue
- Journal of the American College of Surgeons
- Published
- 2019-07
- Volume
- 229
- Issue
- 1
- Pages
- 58-67e1
- ISSN
- 1072-7515 (ISSN-L)
- PMC
- PMC6599553
- OpenAlex
- W2939032636
- Cited by
- 46
- References
- 37
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 7 · 2020: 6 · 2019: 1
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American College of Surgeons (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01 GM-113945, T32 GM008721, P50 GM-111152)
- National Institute on Aging (R03 AG056444, P30 AG028740)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- glucagon-like peptide-1, sepsis, chronic critical illness, critically ill surgical patients, interleukin-6, mortality prediction, functional disability, multiple organ failure, septic shock, catabolic state, muscle atrophy, biomarkers
- MeSH terms
- Aged, Chronic Disease, Female, Florida, Follow-Up Studies, Humans, Intensive Care Units, Male, Middle Aged, Prospective Studies, Surgical Wound Infection, Time Factors, Biomarkers, Incidence, Survival Rate, Critical Illness, Sepsis, Glucagon-Like Peptide 1
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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