Material-driven glucose responsiveness in insulin delivery systems: carrier selection and performance

Conventional subcutaneous insulin therapy faces limitations in patient adherence and carries a persistent risk of hypoglycemia, primarily due to the challenges of achieving precise dosing. To address this, glucose-responsive insulin delivery systems have been developed to autonomously adjust insulin release in direct response to real-time fluctuations in blood glucose levels. This approach offers a promising pathway toward achieving more physiological glycemic control. This review systematically summarizes recent advances in the design of such intelligent systems, with a focus on two fundamentally interconnected components: the ongoing evolution of glucose-sensing mechanisms, which encompass enzymatic, non-enzymatic, and transporter-mediated strategies, and the parallel development of advanced carrier materials, including metal-organic frameworks, smart polymers, and bio-derived materials. In addition to outlining these technological developments, this work provides a balanced analysis of the operational principles, relative merits, and key translational challenges inherent in current system designs, with particular attention to long-term biocompatibility, stability, and safety. By presenting a coherent synthesis of the field's current landscape and its potential future directions, this review aims to inform and support the rational development of next-generation glucose-responsive insulin therapies with stronger prospects for clinical translation.