Abstract: Background Horses experience metabolic derangements in systemic inflammatory response syndrome (SIRS). Metformin modulates oxidative and metabolic processes in vitro across species and improves outcomes in human SIRS/sepsis, but its effects in vivo in horses is not known.
Hypothesis: Metformin will mitigate metabolic and oxidative responses in experimentally-induced equine SIRS.
Animals Nine university-owned mixed-breed horses
Methods Horses received saline or endotoxin (E. coli O111:B4, 30 ng/kg) followed by metformin (11.7 mg/kg IV, Calbiochem®, after sterile filtration) or saline placebo 30 minutes later in a randomized cross-over design. Serial blood samples were collected for 24 hours to quantify plasma oxidative markers, lactate, glucose, insulin, glucagon-like polypeptide-1 (GLP-1), and cortisol. Effects of time and treatment were analyzed via repeated-measures ANOVA (P < 0.05).
Results Endotoxin exposure increased insulin, GLP-1, and cortisol concentrations compared to baseline with peak concentrations at 2 hours after endotoxin (P < 0.041). No differences in these parameters, or in plasma oxidative metabolites, antioxidant capacity, glucose, or lactate between metformin- and placebo-treated horses were detected (P > 0.305). Endotoxin-induced plasma GLP-1 concentrations returned to baseline levels by 25 hours post-endotoxin in metformin treated horses (P = 0.996), but not in placebo-treated horses (P = 0.041).
Conclusions and Clinical Importance: A single dose of intravenous metformin did not substantially alter oxidative or metabolic responses to experimental SIRS in horses but did shorten the duration of the endotoxin-induced incretin response. Further study is needed to determine the clinical consequences of this effect and to investigate potential metformin dosing regimens in equine SIRS.
