Microneedle-Based Multiplexed Monitoring of Diabetes Biomarkers: Capabilities Beyond Glucose Toward Closed-Loop Theranostic Systems

Significant advances have been made in the management of diabetes through the development of wearable biomedical monitoring and drug-delivery devices. Technologies such as continuous glucose monitors (CGMs) and insulin pumps have particularly transformed diabetes care over the past two decades. However, most current efforts largely focus on glucose and insulin regulation, limiting a broader understanding of metabolic health and the interplay of various biomarkers. Comprehensive diabetes management requires a more holistic approach encompassing diverse biomarkers to address the full spectrum of metabolic health. Adequate response to glycemic variability thus requires continuous monitoring of additional chemical and physical parameters that affect insulin sensitivity. Leveraging recent advances in wearable microneedle (MN) platforms, such systems have received considerable attention for biomedical applications, ranging from continuous multiplexed monitoring to transdermal drug delivery. This review article provides a thorough analysis of the use of MNs for enhanced diabetes management, emphasizing their unique capabilities for simultaneous monitoring of multiple key diabetes biomarkers beyond glucose and for autonomous transdermal delivery of insulin and glucagon based on novel glucose-responsive MN materials and addressing literature gaps regarding the integration of such diagnostic and treatment technologies onto single MN arrays. Representative applications of key MN sensing and delivery devices are highlighted, underscoring their capabilities to revolutionize disease management. We conclude with a forward-looking vision of next-generation AI-guided MN-based closed-loop "Sense-Release" artificial pancreas systems for enhanced glycemic control and improved patient outcomes.