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Significant advanced have recently been made in exploiting microneedle-based (MN-based) diabetes devices for minimally invasive wearable biosensors and for continuous glucose monitoring. Within this emerging class of skin-worn MN-based sensors, the ISF can be utilized as a rich biomarker source to diagnose diabetes. While initial work of MN devices focused on ISF extraction, the recent research trend has been oriented toward developing in vivo glucose sensors coupled with optical or electrochemical (EC) instrumentation. This outlook highlights the essential characteristics of the sensing mechanisms, rational design, sensing properties, and applications. Finally, we describe the opinions about the challenge and prospects of optical and EC MN-based device platforms for the fabrication of wearable biosensors and their application potential in the future.