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

Tania Rivero, Alan G Fraser, Christoph Stettler, Markus Laimer, Faina Wehrli, Lum Kastrati, Arjola Bano, Lia Bally, Roman Hovorka, Angelica Valz Gris, Juri Künzler, Adea Llane

Journal: Diabetes, obesity & metabolism 2024;26(10):4753-4766

PMID: 39143655

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Plain Language Summary

Managing blood glucose levels is essential for people with diabetes to prevent complications such as heart disease, kidney damage, and nerve problems. In recent years, several high-risk medical devices have been developed to improve blood sugar control. These include automated insulin delivery (AID) systems, implantable insulin pumps, and continuous glucose monitoring (CGM) devices. In Europe, such devices receive CE marking before entering the market, but concerns have been raised about whether sufficient high-quality clinical evidence supports their approval and long-term use. This study systematic review and meta-analysis examined the clinical evidence for high-risk CE-marked medical devices used in blood sugar management.

The results showed that automated insulin delivery systems were associated with improved blood sugar control. However, the quality of evidence varied across devices. Not all studies were randomised, and around 26% reported industry funding, which may introduce potential bias. Evidence for implantable insulin pumps was more limited compared to AID systems and CGM devices. Safety outcomes were generally acceptable, but long-term independent data were less consistently available.

In conclusion, while some high-risk CE-marked glucose management devices, particularly AID systems, are supported by moderate-to-strong clinical evidence, the overall evidence base is heterogeneous. The proportion of non-randomised studies and industry-funded research highlights the need for continued independent, high-quality trials. Healthcare professionals can use these findings to evaluate the strength of evidence behind device-based blood sugar management and to support shared decision-making with patients.

Abstract

AIMS

To conduct a systematic review and meta-analysis, within the Coordinating Research and Evidence for Medical Devices (CORE-MD) project, evaluating CE-marked high-risk devices for glucose management.

MATERIALS AND METHODS

We identified interventional and observational studies evaluating the efficacy and safety of eight automated insulin delivery (AID) systems, two implantable insulin pumps, and three implantable continuous glucose monitoring (CGM) devices. We meta-analysed randomized controlled trials (RCTs) comparing AID systems with other treatments.

RESULTS

A total of 182 studies published between 2009 and 2024 were included, comprising 166 studies on AID systems, six on insulin pumps, and 10 on CGM devices; 26% reported industry funding; 18% were pre-market; 37% had a comparator group. Of the studies identified, 29% were RCTs, 24% were non-randomized trials, and 47% were observational studies. The median (interquartile range) sample size was 48 (28-102), age 34.8 (14-44.2) years, and study duration 17.5 (12-26) weeks. AID systems lowered glycated haemoglobin by 0.5 percentage points (absolute mean difference [MD] = -0.5; 21 RCTs; I = 86%) and increased time in target range for sensor glucose level by 13.4 percentage points (MD = 13.4; 14 RCTs; I = 90%). At least one safety outcome was assessed in 71% of studies.

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.

Address: Department of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.; Department of Cardiology, Inselspital, Bern University Hospital, Bern, Switzerland.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.; Department of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Graduate School for Health Sciences, University of Bern, Bern, Switzerland.; Medical Library, University Library of Bern, University of Bern, Bern, Switzerland.; Epistudia, Bern, Switzerland.; Section of Hygiene, University Department of Health Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy.; Department of Cardiology, University Hospital of Wales, Cardiff, UK.; Wellcome Trust, MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

DOI: 10.1111/dom.15849