Clinical evidence for high-risk CE-marked medical devices for glucose management: a systematic review and meta-analysis

Aims: High-risk medical devices are increasingly used in diabetes management, but there are no specific European recommendations on how they should be evaluated. Within the Coordinating Research and Evidence for Medical Devices (CORE-MD) project, we conducted a systematic review and meta-analysis evaluating CE-marked high-risk devices for glucose management. Materials and Methods: We identified interventional and observational studies evaluating the efficacy and safety of 8 automated insulin delivery (AID) systems, 2 implantable insulin pumps, and 3 implantable continuous glucose monitoring (CGM) devices. We meta-analysed randomized controlled trials (RCTs) comparing AID systems with other treatments. Results: 99 studies published from 2009–2022 were included, comprising 83 on AID systems, 6 on insulin pumps, and 10 on CGM; 43% reported industry funding;30% were pre-market; 45% had a comparator group. 33% were RCTs, 25% non-randomized trials, and 41% observational studies. Median sample size was 52 (interquartile range 25–111), age 37.8 years (17–45.5), and study duration 13 weeks (4.5–26). AID systems lowered HbA1c by 0.3 percentage points (absolute mean difference [MD]=-0.3; 9 RCTs; I2=85%) and increased time in target range for sensor glucose level by 10.5 percentage points (MD=10.5; 14 RCTs; I2=89%). 69% of studies reported on at least one safety outcome. Conclusions: High-risk devices for glucose monitoring or insulin dosing, in particular AID systems, improve glucose control safely but evidence on diabetes-related end organ damage is lacking due to short study durations. Methodological heterogeneity highlights the need for developing standards for future pre- and post-market investigations of diabetes-specific high-risk medical devices.