Immunotherapy for Type 2 Diabetes: Mechanisms and Therapeutic Advances

ABSTRACT Diabetes mellitus (DM) is a chronic metabolic disorder characterised by persistent hyperglycemia, systemic metabolic dysfunction and insulin resistance (IR). Recent progress in the interplay between the immune system and metabolism highlights the critical role of immune dysregulation in the pathogenesis of IR and type 2 diabetes mellitus (T2DM). This review explores the immunopathogenic mechanisms underlying IR and the potential immunotherapies to modulate these pathways, with a focus on immune cells, inflammatory mediators and immune checkpoint regulation. Recent advances in immunotherapy have opened new avenues for restoring metabolic homeostasis and improving insulin sensitivity. Targeted approaches, including monoclonal antibodies against TNF‐α, IL‐1β and IL‐6, have been reported to have antifibrotic and anti‐inflammatory effects, reducing inflammation‐driven insulin resistance. Additionally, inhibitors of NF‐κB, JAK/STAT and JNK signalling pathways have been reported to enhance insulin sensitivity. Immunoregulatory therapeutics using MSC (mesenchymal stem cell) and Treg (regulatory T cell) therapy and cytokine vaccine‐based vaccines are emerging as innovative therapeutic options for T2DM. Despite these advances, problems such as immune‐related toxic reactions, patient and individual‐specific variability, and the requirement for precision medicine approaches persist as obstacles to translational application from the clinics to industry levels. In this review, an overview of preclinical and clinical evidence for immunotherapeutic approaches to IR is described, and recommendations for future developments in integrating these therapies into personalised diabetes management are provided. Targeting immune‐mediated inflammation with immunotherapies can lead to a new era in T2DM therapy, which will provide new approaches to enhance insulin sensitivity and glycemic control.