Glycaemic control in type 1 diabetes during real time continuous glucose monitoring compared with self monitoring of blood glucose: meta-analysis of randomised controlled trials using individual patient dataBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d3805 (Published 07 July 2011) Cite this as: BMJ 2011;343:d3805
- John C Pickup, professor of diabetes and metabolism1,
- Suzanne C Freeman, medical statistics student23,
- Alex J Sutton, professor of medical statistics2
- 1Diabetes Research Group, Division of Diabetes and Nutritional Sciences, King’s College London School of Medicine, Guy’s Hospital, London SE1 1UL, UK
- 2Department of Health Sciences, University of Leicester, Leicester, UK
- 3MRC Clinical Trials Unit, London
- Correspondence to: J C Pickup
- Accepted 12 May 2011
Objective To determine the clinical effectiveness of real time continuous glucose monitoring compared with self monitoring of blood glucose in type 1 diabetes.
Design Meta-analysis of randomised controlled trials.
Data sources Cochrane database for randomised controlled trials, Ovid Medline, Embase, Google Scholar, lists of papers supplied by manufacturers of continuous glucose monitors, and cited literature in retrieved articles.
Studies reviewed Randomised controlled trials of two or more months’ duration in men and non-pregnant women with type 1 diabetes that compared real time continuous glucose monitoring with self monitoring of blood glucose and where insulin delivery was the same in both arms.
Analysis Two step meta-analysis of individual patient data with the primary outcome of final glycated haemoglobin (HbA1c) percentage and area under the curve of hypoglycaemia (glucose concentration <3.9 mmol/L) during either treatment, followed by one step metaregression exploring patient level determinants of HbA1c and hypoglycaemia.
Results Six trials were identified, consisting of 449 patients randomised to continuous glucose monitoring and 443 to self monitoring of blood glucose. The overall mean difference in HbA1c for continuous glucose monitoring versus self monitoring of blood glucose was −0.30% (95% confidence interval −0.43% to −0.17%) (−3.0, −4.3 to −1.7 mmol/mol). A best fit regression model of determinants of final HbA1c showed that for every one day increase of sensor usage per week the effect of continuous glucose monitoring versus self monitoring of blood glucose increased by 0.150% (95% credibility interval −0.194% to −0.106%) (1.5, −1.9 to −1.1 mmol/mol) and every 1% (10 mmol/mol) increase in baseline HbA1c increased the effect by 0.126% (−0.257% to 0.0007%) (1.3, −2.6 to 0.0 mmol/mol). The model estimates that, for example, a patient using the sensor continuously would experience a reduction in HbA1c of about 0.9% (9 mmol/mol) when the baseline HbA1c is 10% (86 mmol/mol). The overall reduction in area under the curve of hypoglycaemia was −0.28 (−0.46 to −0.09), corresponding to a reduction in median exposure to hypoglycaemia of 23% for continuous glucose monitoring compared with self monitoring of blood glucose. In a best fit regression model, baseline area under the curve of hypoglycaemia was only weakly related to the effect of continuous glucose monitoring compared with self monitoring of blood glucose on hypoglycaemia outcome, and sensor usage was unrelated to hypoglycaemia at outcome.
Conclusions Continuous glucose monitoring was associated with a significant reduction in HbA1c percentage, which was greatest in those with the highest HbA1c at baseline and who most frequently used the sensors. Exposure to hypoglycaemia was also reduced during continuous glucose monitoring. The most cost effective or appropriate use of continuous glucose monitoring is likely to be when targeted at people with type 1 diabetes who have continued poor control during intensified insulin therapy and who frequently use continuous glucose monitoring.
We thank the trialists and trial sponsors for supplying individual patient data. Reman McDonagh provided invaluable help in data collection.
Contributors: JCP initiated and designed the study, collected the individual patient data from trialists and other sources, and extracted and reviewed summary data from published articles with SCF. SCF and AJS carried out the statistical analysis. All authors contributed to data interpretation and to the final version of the manuscript. JCP is the guarantor.
Funding: SCF was supported by the Engineering and Physical Sciences Research Council.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that: no authors had support from companies for the submitted work; JCP has received speaker and advisory board honorariums from Medtronic, a manufacturer of continuous glucose monitoring devices that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
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