The present invention relates to instruments and methods related to the in vivo analytical performance of percutaneously implanted nitric oxide (NO)-releasing amperometric glucose biosensors. Needle-type glucose biosensors can be functionalized with NO-releasing polyurethane coatings designed to release similar total amounts of NO for rapid or slower (greater than 3 day) durations and remain functional as outer glucose sensor membranes. Relative to controls, NO-releasing sensors were characterized with improved numerical accuracy on days 1 and 3. Furthermore, the clinical accuracy and sensitivity of rapid NO-releasing sensors were superior to control and slower NO-releasing sensors at both 1 and 3 days implantation. In contrast, the slower, extended NO releasing-sensors were characterized by shorter sensor lag times (<4.2 min) in response to intravascular glucose tolerance tests versus burst NO-releasing and control sensors (>5.8 min) at 3, 7, and 10 d. Collectively, these results highlight the potential for NO release to enhance the analytical utility of in vivo glucose biosensors. Thus, the analytical performance benefit is dependent on the NO-release duration.