EVANS et al. study

Meta-analysis of real-world observational studies by Evans et al.¹

Sustained Impact of Flash Glucose Monitoring 
on Glycaemic Control¹

The meta-analysis by Evans and colleagues evaluated 75 trials encompassing >30,000 participants with type 1 (n = 28,063; 62 trials) and type 2 diabetes (n = 2,415; 13 trials) (T1D and T2D) using the FreeStyle Libre system over periods from 1 to 24 months.

Use of the FreeStyle Libre system significantly reduced HbA1c levels in adults and children with T1D and in adults with T2D. Greater reductions in HbA1c were seen in users with higher baseline HbA1c. HbA1c reductions were sustained for 24 months in adults and children with T1D and for 12 months in adults with T2D.

Significant and sustained reduction in HbA1c with FreeStyle Libre system¹

Use of the FreeStyle Libre system was associated with significant reductions in HbA1c that were sustained for 24 months in adults and children with
T1D and for 12 months in adults with T2D.

Study objective

Extend a previous analysis of real-world reductions in HbA1c in individuals with T1D and T2D using the FreeStyle Libre system versus self-monitoring blood glucose²

Investigate whether HbA1c reductions are sustained over 24 months

Identify patterns of change in HbA1c for users of the FreeStyle Libre system living with T1D or T2D¹

Study design & study population

A search for relevant publications was conducted across key abstracting and indexing databases.* The search covered the period from 2013 until December 31^st 2020.

75 studies were identified that reported longitudinal laboratory HbA1c data in participants with T1D or T2D using the FreeStyle Libre system over periods from 1 to 24 months. All studies reported data in a manner that could be used in a statistical meta-analysis.

For randomised controlled trials within the analysis set, within-intervention arm results were included, but not the between-arm results reported previously. All studies were reported as absolute change from baseline to ensure a consistent approach and to reflect the real-world patient- centred outcome.

The meta-analysis centred on observed change in HbA1c at 3–4 months and 4.5–7.5 months, as well as a longitudinal analysis up to 24 months. Mean change in HbA1c adjusted for initial HbA1c was estimated using random effects meta- regression versus initial HbA1c by type of diabetes with type of diabetes, month, and interaction of type of diabetes and month as fixed effects. Separate analyses were conducted for adults and children.

Study results were published online in the expert journal Diabetes Therapy in April, 2022.¹

Flowchart / study selection protocol by Evans et al. (2022).

Study selection flow diagram

Study results

Use of FreeStyle Libre system resulted in significant and sustained reductions in HbA1c in adults with T1D or T2D and in children with T1D.

Change in HbA1c in adults at 3–4 and 4.5–7.5 months after starting the FreeStyle Libre system¹
A total of 75 studies with outcomes data from 30,478 participants were included in the analysis. Meta-analysis of overall mean change in HbA1c after starting the FreeStyle Libre system at each timepoint is shown in Table 1. 

In adults, reductions in HbA1c were evident 3 months after initiating FreeStyle Libre system, with a fall of HbA1c of -0.53% in T1D users and -0.45% in T2D users.
At 4.5–7.5 months post-initiation, HbA1c was reduced by -0.42% in T1D participants and -0.59% in those with T2D.

Longitudinal change in HbA1c in adults with T1D and T2D¹
The use of the FreeStyle Libre system resulted in a rapid and sustained reduction in HbA1c in adults with T1D and T2D, with no significant differences observed between T1D and T2D (Figure 1).

Figure 1 – This longitudinal plot of adjusted mean change in HbA1c versus time for adults with T1D or T2D shows substantial overlap of the confidence intervals for T2D and T1D at each timepoint.

Correlation between reductions in HbA1c and baseline HbA1c in adults¹

At the 4.5 – 7.5-month timepoint, every percentage point increase in mean starting HbA1c was associated with 0.49% reduction in adult FreeStyle Libre system users with T1D (starting HbA1c > 7.2%) and an 0.35% decline in adult users with T2D (starting HbA1c > 6.7%) (Figure 2).
These gains persisted throughout the time period for which data exist (up to 24 months in T1D, up to 12 months in T2D).

Figure 2 – Meta-regression analysis of mean change in HbA1c versus mean initial HbA1c as a bubble chart. The area of each bubble represents the weight of the trial. The regression line from meta-regression random effects model is displayed.

Mean change in HbA1c over 24 months in children and adolescents with T1D¹

In children and adolescents using the FreeStyle Libre system, the greatest reduction in mean HbA1c (-0.54%) was seen after 1 month (Figure 3).
This effect lessened with time up to 15 months, after which the reduction appeared to stabilize through 24 months.

Figure 3 – Figure showing longitudinal plot of adjusted mean change in HbA1c over time for children and adolescents with T1D. The dotted line above the adjusted baseline indicates the predicted rise in mean HbA1c with age in children and adolescents observed by Rosenbauer et al.³

Study limitations

Only flash glucose monitoring arms were considered in this analysis, with no comparison to control subjects, since many of the real-world observational studies did not contain a control group. 
There may be a bias in the recruitment of the patients. Entry criteria were not standardised across the studies with few eligibility criteria specified. 
There is potential publication bias. 
Not all studies reported how missing data were handled.

Summary

Using the FreeStyle Libre system results in a significant reduction in HbA1c for adults and children with T1D and for adults with T2D¹.

HbA1c in adult participants fell within the first 3 – 4 months after starting the FreeStyle
Libre system and this reduction was maintained to 24 months in users with T1D and to
12 months in users with T2D.

No significant differences in HbA1c outcomes were detected between adults with T1D or
T2D.

HbA1c in children and adolescents with T1D showed the greatest reduction 1 month
after starting FreeStyle Libre system (-0.54%), after which the effect lessened and
appeared to stabilise through 24 months; this may reflect age related changes in mean
HbA1c.

Reductions in HbA1c were correlated with baseline HbA1c in FreeStyle Libre system
users, with greater reduction seen in those with higher baseline HbA1c.

The data from this study was collected using the FreeStyle Libre system. The FreeStyle Libre 2 and FreeStyle Libre 3 systems have the same features as the FreeStyle Libre system with real-time glucose alerts. Therefore, the study data are applicable to both products.

* A comprehensive list of search criteria can be found in the publication.¹

References & Disclaimers

Images are for illustrative purposes only. Not real patient data.

1. Evans M, et al. Reductions in A1c with flash glucose monitoring are sustained for up to 24 months: A meta-analysis of 75 real-world observational studies. Diabetes Ther. 2022; 1175–1185. DOI: 10.1007/s13300-022-01253-9.

2. Evans M, et al. The impact of flash glucose monitoring on glycaemic control as measured by A1c: A meta-analysis of clinical trials and real-world observational studies. Diabetes Ther. 2020;11(1)83–95. DOI: 10.1007/s13300-019-00720-0...

3. Rosenbauer J, et al. Improved metabolic control in children and adolescents with type 1 diabetes. Diabetes Care. 2012;35:80–6.

* A comprehensive list of search criteria can be found in the publication.¹

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EVANS et al. study

Meta-analysis of real-world observational studies by Evans et al.¹

Sustained Impact of Flash Glucose Monitoring 
on Glycaemic Control¹