Table 2.

Representative preclinical evidence in infection and infection-related models

Model and intervention	Pathogen outcome	Host outcome	Mechanistic interpretation and limitation	Reference(s)
P. aeruginosa Xen5 pneumonia–sepsis; liraglutide 2 mg/kg s.c., 30 min after infection	Reduced bacterial burden	Improved survival and surfactant indices; reduced lung injury	Supports both pathogen control and host tolerance; single strain, dose and short observation window	[13]
Diabetic P. aeruginosa pneumonia; Exendin-4 pretreatment for 7 days and continued dosing	Not measured	Reduced lung inflammation and pathology	Evidence in a metabolically high-risk host; pretreatment design and no burden/survival endpoint	[145]
P. aeruginosa airway mucus model; Exendin-4 during infection/post-infection protocols	Reduced lung bacterial burden	Improved FOXA2-related mucus homeostasis	More representative of chronic mucus-dysregulated airway disease than typical community-acquired pneumonia	[146]
CLP polymicrobial sepsis; liraglutide pretreatment	Not a principal endpoint	Improved endothelial function; reduced vascular inflammation and oxidative stress	Primarily supports endothelial and microcirculatory protection; prophylactic exposure	[147]
LPS-induced acute lung injury; dulaglutide treatment	Not applicable: no live pathogen	Reduced lung inflammation, oxidative stress and apoptosis	Supports an anti-inflammatory lung-protection mechanism only; LPS cannot establish pathogen clearance or infection efficacy	[11]
Caecal-slurry/hyperoxia two-hit lung injury; liraglutide pretreatment	No consistent reduction in pathogen burden	Reduced oedema, inflammation and alveolar–capillary injury	Predominantly supports host tolerance; composite model, prophylactic dosing and short follow-up	[12]
TLR challenge and polymicrobial sepsis; GLP-1R agonism with cell-specific Glp1r loss	Not a principal endpoint	Reduced TNF, sickness behaviour, hypothermia and lung injury	Supports a neuronal contribution to systemic host-response regulation; pathogen clearance was not established	[9]
PR8 H1N1 influenza; liraglutide from inoculation to day 2	Viral NP mRNA reduced; infectious titre not measured	Improved survival and interferon-related responses	Possible resistance signal, but viral-burden assessment was indirect	[116]
H9N2 influenza; liraglutide during the infection protocol	Viral titre unchanged	Reduced mortality, lung injury, and inflammatory indices	Predominantly supports host tolerance rather than antiviral activity	[148]
Experimental cerebral malaria; liraglutide from day 4 after infection	Parasitaemia unchanged	No meaningful survival or neurological benefit	Negative evidence against extrapolating benefit across pathogen classes	[149]

LPS models reproduce selected inflammatory components but do not contain replicating pathogens. The “Pathogen outcome” column distinguishes direct measures of pathogen burden/clearance from host-response outcomes. Abbreviations: CLP caecal ligation and puncture, FOXA2 forkhead box A2, LPS lipopolysaccharide, NP nucleoprotein, s.c. subcutaneous, TLR Toll-like receptor, TNF tumour necrosis factor