Diabetes mellitus (DM) is a multifactorial metabolic disorder associated with systemic inflammation and vascular complications. Pentraxin-3 (PTX3) has emerged as a key biomarker of inflammation and endothelial dysfunction in DM. We aimed to examine the role of PTX3 in DM and assesses the impact of pharmacological interventions on its expression. The review included studies analyzing PTX3 modulation by antidiabetic therapies, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 agonists (GLP-1a), and dipeptidyl peptidase-4 inhibitors (DPP-4i), as well as the effects of lifestyle interventions. Clinical and experimental studies demonstrated a strong correlation between PTX3 levels and DM progression. Elevated PTX3 levels were associated with diabetic complications, including nephropathy, retinopathy, and cardiovascular diseases. Antidiabetic drugs showed differential effects on PTX3 expression, with GLP-1a and DPP-4i significantly reducing PTX3 levels, while SGLT-2i displayed a paradoxical increase. Lifestyle interventions, including dietary modifications and weight loss, yielded inconsistent effects, suggesting genetic and metabolic factors influence PTX3 regulation. While pharmacological therapies, particularly GLP-1a and DPP-4i, demonstrate anti-inflammatory effects, further research is needed to standardize PTX3 measurement and explore its potential as a therapeutic target. Personalized treatment strategies incorporating genetic profiling may optimize inflammation control and disease management in DM patients.

Type 2 diabetes mellitus is associated with chronic low-grade inflammation contributing to endothelial dysfunction, metabolic imbalance, and cardiovascular complications. Although semaglutide (SEM) and tirzepatide (TIR) provide important metabolic and cardioprotective benefits, their early anti-inflammatory effects and potential sex-dependent differences remain incompletely understood. This study comparatively evaluated the effects of SEM and TIR on systemic inflammatory biomarkers in a murine model of streptozotocin-induced diabetes mellitus. Thirty BALB/c mice were allocated into six experimental groups according to sex and treatment: control, SEM, and TIR groups (n = 5/group). Diabetes was induced by intraperitoneal streptozotocin administration, followed by treatment with SEM or TIR. Circulating interleukin-1β (IL-1β) and pentraxin-3 (PTX-3) levels were measured at baseline, one week after streptozotocin administration, and after six weeks of treatment. Control groups exhibited progressive increases in IL-1β and PTX-3 levels, indicating sustained inflammatory activation. In contrast, SEM- and TIR-treated animals showed attenuated inflammatory responses characterized by transient or stabilized biomarker profiles. Differential inflammatory responses were observed between treatments and sexes. Male SEM and Male TIR groups demonstrated stable IL-1β levels, whereas female treated groups showed persistent elevations, particularly Female TIR animals. PTX-3 responses also displayed differential sex-dependent patterns, with Female SEM animals exhibiting the most stable inflammatory profile. These findings suggest differential early immunomodulatory effects of the two modern antidiabetic drugs, characterized by distinct biomarker responses according to sex and inflammatory marker profile. IL-1β and PTX-3 may represent complementary biomarkers for the assessment of early inflammatory activation associated with diabetes mellitus and its cardiometabolic complications.