Hepatic biomarker trajectories and mortality in septic adults with type 2 diabetes and recorded dipeptidyl peptidase-4 inhibitor exposure versus metformin-based therapy: A propensity-score-matched cohort study.
5 affiliations
- 1Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
- 2Third Department of Psychiatry, Agioi Anargyroi General Oncological Hospital of Kifisia, National and Kapodistrian University of Athens, Athens, Greece.
- 3BIOSIM Laboratory, School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece.
- 4Department of Electrical and Electronic Engineering, University of West Attica, Thivon Avenue 250, Athens, 122 44, Greece.
- 5Global Business School for Health, University College London, London, WC1E 6BT, UK.
Abstract
Aims
To determine whether recorded dipeptidyl peptidase-4 (DPP-4) inhibitor exposure, compared with metformin, is associated with worse hepatic biomarker trajectories or mortality in adults with type 2 diabetes and sepsis.Methods
In three critical care databases (MIMIC-IV, eICU-CRD, NWICU), adults with type 2 diabetes and sepsis with a DPP-4 inhibitor record were matched 1:3 within each database to metformin comparators on age, sex, body mass index, 24-h SOFA and day-1 estimated glomerular filtration rate. The day 1-7 total bilirubin trajectory was analysed by linear mixed-effects regression under nine specifications including log transformation, flexible day terms, doubly robust adjustment and inverse-probability-of-observation weighting.Results
Matching yielded 105 DPP-4 inhibitor and 297 metformin patients; a pre-admission exposure record was present in 60.0%. The between-group difference in bilirubin slope was +0.048 mg/dL/day (95% CI -0.029 to 0.126; p = 0.221), with p between 0.109 and 0.436 across specifications. No other hepatic outcome survived multiplicity correction. Alkaline phosphatase rose more steeply on the primary specification (+6.97 U/L/day; q = 0.005) but was fragile: 12 of 28 sensitivity analyses retained p < 0.05. In-hospital mortality was 21.0% versus 13.5% (risk ratio 1.56, 95% CI 0.97-2.49), attenuating to 1.23 (0.67-2.29) with documented pre-admission exposure.Conclusions
There was no statistically detectable difference in bilirubin trajectory between recorded DPP-4 inhibitor and metformin exposure, although differences below the cohort's detectable-effect threshold cannot be excluded. An ALP signal was fragile and hypothesis-generating. Mortality findings are exploratory and non-causal. These associations with recorded exposure cannot inform inpatient management.
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BibTeX
@article{alevizopoulos2026hepatic,
title = {{Hepatic biomarker trajectories and mortality in septic adults with type 2 diabetes and recorded dipeptidyl peptidase-4 inhibitor exposure versus metformin-based therapy: A propensity-score-matched cohort study.}},
author = {Aristomenis G Alevizopoulos and Georgios G Anastasiou and Paraskevas Nomikos and Iakovos Kritikos},
journal = {Metabolism open},
year = {2026},
month = oct,
doi = {10.1016/j.metop.2026.100508},
url = {https://europepmc.org/article/MED/42898695},
note = {CC BY},
}
RIS
TY - JOUR
TI - Hepatic biomarker trajectories and mortality in septic adults with type 2 diabetes and recorded dipeptidyl peptidase-4 inhibitor exposure versus metformin-based therapy: A propensity-score-matched cohort study.
AU - Aristomenis G Alevizopoulos
AU - Georgios G Anastasiou
AU - Paraskevas Nomikos
AU - Iakovos Kritikos
PY - 2026
DA - 2026/10/10
JO - Metabolism open
DO - 10.1016/j.metop.2026.100508
UR - https://europepmc.org/article/MED/42898695
AB - Aims To determine whether recorded dipeptidyl peptidase-4 (DPP-4) inhibitor exposure, compared with metformin, is associated with worse hepatic biomarker trajectories or mortality in adults with type 2 diabetes and sepsis.Methods In three critical care databases (MIMIC-IV, eICU-CRD, NWICU), adults with type 2 diabetes and sepsis with a DPP-4 inhibitor record were matched 1:3 within each database to metformin comparators on age, sex, body mass index, 24-h SOFA and day-1 estimated glomerular filtration rate. The day 1-7 total bilirubin trajectory was analysed by linear mixed-effects regression under nine specifications including log transformation, flexible day terms, doubly robust adjustment and inverse-probability-of-observation weighting.Results Matching yielded 105 DPP-4 inhibitor and 297 metformin patients; a pre-admission exposure record was present in 60.0%. The between-group difference in bilirubin slope was +0.048 mg/dL/day (95% CI -0.029 to 0.126; p = 0.221), with p between 0.109 and 0.436 across specifications. No other hepatic outcome survived multiplicity correction. Alkaline phosphatase rose more steeply on the primary specification (+6.97 U/L/day; q = 0.005) but was fragile: 12 of 28 sensitivity analyses retained p < 0.05. In-hospital mortality was 21.0% versus 13.5% (risk ratio 1.56, 95% CI 0.97-2.49), attenuating to 1.23 (0.67-2.29) with documented pre-admission exposure.Conclusions There was no statistically detectable difference in bilirubin trajectory between recorded DPP-4 inhibitor and metformin exposure, although differences below the cohort's detectable-effect threshold cannot be excluded. An ALP signal was fragile and hypothesis-generating. Mortality findings are exploratory and non-causal. These associations with recorded exposure cannot inform inpatient management.
SN - 2589-9368
ER -