LIBERATES: Hypoglycemia reduction with post-ACS flash monitoring in type 2 diabetes
medwireNews: The results of the phase 2 LIBERATES trial suggest that flash glucose monitoring could reduce the time people with type 2 diabetes spend in hypoglycemia in the period following an acute coronary syndrome (ACS).
The researchers focused on this subgroup due to their high cardiovascular risk. Introducing the trial for delegates at the virtual 56th EASD Annual Meeting, Robert Storey (University of Sheffield, UK) outlined the large loss of life expectancy, high risk of repeat events, and the uncertain benefits of controlling blood glucose, with both high and low levels associated with adverse outcomes.
But he noted that studies to date addressing glucose control have employed “superficial” assessment of blood glucose and been unable to quantify hypoglycemia, which has been specifically linked to adverse cardiovascular events in people with type 2 diabetes, potentially by contributing to an extended fibrin clot lysis time.
The LIBERATES team therefore randomly assigned people with type 2 diabetes, recruited within 5 days of hospital admission for ACS, to use flash glucose monitoring with the Freestyle Libre or to continue using self-monitored blood glucose (SMBG) plus blinded continuous monitoring with the Libre Pro.
Trial participants had to be taking a sulfonylurea or insulin, but could be taking other medications as well.
Trial statistician Deborah Stocken (University of Leeds, UK) explained that because the Freestyle Libre collects a maximum of 8 hours’ data on the monitor before it is overwritten, the participants were asked to scan the device a minimum of every 8 hours to ensure they collected the full day’s worth of data. The primary outcome was time in range during the 14 days up to day 91 and was based only on days in which at least 80% of data was recorded.
In practice, the 141 study participants scanned the device around six times a day, reported principal investigator Ramzi Ajjan (University of Leeds), and this rate remained consistent throughout the trial.
The participants were a median age of 63 years, 73% were male, and they had a median BMI of 31 kg/m2 and diabetes duration of 13 years. The most common comorbidity was coronary artery disease, in 27%.
Principal investigator Ramzi Ajjan discusses the LIBERATES trial (11:40).
Overall, using Bayesian analysis, the researchers found that the flash monitoring group spent an additional 17 minutes per 24 hours with their blood glucose within the range of 3.9–10.0 mmol/L (70–180 mg/dL), compared with the SMBG group, although this did not meet the team’s predefined statistical cutoff.
“The take-home message from this Bayesian analysis – because a lot of people are not familiar with this – is no matter what your preconception is, what you use for the analysis, the data are always moving in favor of the intervention, which is very encouraging,” Ajjan told medwireNews.
In a frequentist analysis, use of flash monitoring resulted in an additional 48 minutes more time in range per day, although this again was not statistically significant.
By contrast, there was a marked reduction in time in hypoglycemia – 80 minutes during the 14 days preceding day 91, with this appearing during days 16–30, although the approximate 45 minute reduction at this point was not statistically significant.
Discussing next steps, Ajjan noted that from a diabetologist point of view the trial showed a large positive effect, given the reduction in time in hypoglycemia and the established benefits of this. “But cardiologists – they want hard endpoint data,” he said, concluding that a phase 3 trial would be warranted if funding can be obtained.
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