scFv-based biologics in diabetes: from therapeutic potential to clinical prospects

The global epidemic of diabetes mellitus the limitations of current therapies-including waning efficacy, adverse effects, and inability to modify disease progression-have accelerated the shift from conventional pharmacotherapy toward biologic agents. This review examines the emergence of single-chain variable fragments (scFv) as a versatile and engineerable class of biotherapeutics for precision diabetes management. Distinguished from full-length monoclonal antibodies (mAbs) by their compact size, enhanced tissue penetration, and modular design, scFv enable precise targeting of both autoimmune and metabolic pathways underlying type 1 diabetes and type 2 diabetes. We summarize advances in scFv applications spanning immunomodulation (e.g., via CTLA-4 and PD-1) and metabolic regulation (e.g., through insulin-degrading enzyme and GLP-1 receptor). Furthermore, we highlight the unique value of avian-derived scFv in recognizing conserved epitopes and overcoming immune tolerance, along with engineering strategies-such as Fc fusion, PEGylation, and multispecific formatting-that enhance pharmacokinetics and therapeutic efficacy. The clinical success of antibodies like Teplizumab underscores the translational potential of antibody-based platforms. Looking forward, scFv-based biologics, particularly when integrated with humanized Fc domains and half-life extension technologies, offer a promising and customizable strategy for next-generation diabetes therapy, bridging innovative drug design with clinically meaningful metabolic and immune modulation.