Miriam E Tucker

September 20, 2016

MUNICH — Use of the Freestyle Libre Flash Glucose Monitoring System (Abbott Diabetes Care) significantly reduces hypoglycemia without raising HbA1c levels in insulin-treated diabetes patients, compared with self-monitoring of blood glucose using finger sticks, new research shows.

The Libre system comprises a small round glucose sensor worn for up to 14 days on the back of the upper arm and a scanner device that the patient waves over the sensor to obtain a reading of glucose concentrations in the interstitial fluid. The scans display both historical and current glucose trends. Glucose measurements can be taken through clothing, and the sensor is water-resistant and can be worn while swimming and bathing.

The system was granted a CE Mark in Europe in 2014 as a replacement for finger-stick glucose monitoring in people with diabetes (any type) down to 4 years of age and is now available in 28 countries, with almost 200,000 users globally.

Patients seem to find the system convenient and many are buying it themselves in markets where it is not yet reimbursed.

It is not yet available in the United States, but Abbott is working on this, company spokesperson Vicky Assardo told Medscape Medical News.

Findings from a multicenter, prospective, nonmasked randomized trial of the Libre compared with usual self blood glucose monitoring in 328 well-controlled patients with type 1 diabetes were published last week in the Lancet by Jan Bolinder, PhD, professor of clinical diabetes research at the Karolinska Institute, Stockholm, Sweden, and colleagues.

And at the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting, Dr Bolinder presented a poster detailing a subgroup analysis of this same trial, showing that the Libre's benefits extended down to patients younger than 25 years, an age group that struggles with glucose monitoring.

Commenting on the overall study findings, Dr Bolinder told Medscape Medical News: "When the patients started using the Libre device, they instantly tripled their rate of self-monitoring, and this resulted in a marked reduction in time and events spent in hypoglycemia, time spent in hyperglycemia, an increase in time spent in optimum range, less glucose variability, and improvements in quality-of-life measurements."

And a commentary accompanying Dr Bolinder's Lancet paper agrees that patients seem to really like this system: "Adherence to flash glucose monitoring was high, which might be related to the convenience of its use.

"This finding is in line with our own personal experience in clinical practice, and many users seem willing to self-fund this technology," note Drs Hood Thabit, Lia Bally, and Roman Hovorka, all of University of Cambridge, United Kingdom.

Another poster presentation at the EASD meeting highlighted a similar efficacy of the device in a study of type 2 patients on intensive insulin treatment.

Debating Pros and Cons: CGM Has Alarms, but Libre Is Easier and Cheaper

Asked to give their views on Libre, experts at the EASD meeting said they felt it would be a good fit for "mainstream" patients who are not yet using the more sophisticated, well-established, methods of tracking glucose, the continuous glucose monitor (CGM) or sensor-augmented insulin pump therapy. Use of these systems varies widely across countries, depending on availability and reimbursement in different healthcare systems, and some patients don't want to use these devices.

And the Libre has one major advantage over CGM in that the need for finger-stick glucose checks for both insulin dosing and calibration are eliminated with the Libre because it is factory-calibrated.

However, the CGM has the benefit of alarms for low and high glucose levels — which the Libre doesn't have, and the lack of these is a downside to the new flash monitoring system, Dr Bolinder acknowledged.

"In certain patient groups such as those with hypoglycemia unawareness, the more sophisticated…systems, especially the sensor-augmented pump systems [which consist of a continuous glucose sensor, an insulin pump, and a transmitter that sends glucose level readings wirelessly from the sensor to the pump] should be used, but I think this [Libre] is for the majority of patients," he commented.

The Libre also doesn't include a "share" feature to allow for remote monitoring by another person, currently available with the Dexcom G5 CGM.

However, Dr Bolinder pointed out that with the Libre "a parent can scan a sleeping child."

Asked to comment, poster session moderator at the EASD meeting, Cornelis J Tack, MD, head of the diabetes section at the Radboud University Nijmegen Medical Center, the Netherlands, noted that the Libre alters the usual paradigm of type 1 management, where patients start out on insulin injections, then move to an insulin pump if still not well-controlled, and then for the "most difficult" patients, a traditional CGM.

"It's been positioned quite differently," he observed.

Dr Tack pointed out that the Libre's accuracy is not better than a CGM, although it doesn't appear to be significantly worse either, despite the lack of use of finger-stick calibrations.

He views the Libre as more "mainstream" than CGM and agrees with Dr Bolinder that because it lacks alarms the device might be most appropriate for patients who don't suffer from hypoglycemic unawareness.

But Steven J Russell, MD, of the Diabetes Research Center at Massachusetts General Hospital, Boston, sees it differently: "It's helpful in the sense that it allows you to get a blood glucose check whenever you want one, and it gives you information about the trends, so it will help you adjust your insulin dosing, but it doesn't have alarms for lows."

"I think for the wider population of type 1s real-time CGM is better. I think the Libre is great for type 2 diabetes, and it's probably better than just finger sticks for type 1s, but I still would prefer real-time CGM," Dr Russell said.

But Libre holds another major advantage: cost. At about €1600 per year, the Libre is considerably less expensive than the CGM in Europe.

And, according to Ms Assardo, "We have had some significant reimbursement successes in Europe in the 2 years since the product became available, including achieving national reimbursement in Austria, Belgium, and Luxembourg and other successes in France, Germany, Italy, and Sweden — with more to come."

Dr Tack said that even though Libre is not yet reimbursed in the Netherlands, many Dutch patients pay for it out of pocket. This means that patients must regard it highly, "because they buy it.…If it becomes cheaper, it will become more and more mainstream."

Dr Bolinder and colleagues agree: "This novel technology could empower individuals with type 1 diabetes by providing an alternative to conventional self-monitoring of blood glucose testing."

Reduces Hypoglycemia by Almost 40% Without Raising HbA1c

The newly published trial of the Libre enrolled 328 adult patients with well-controlled type 1 diabetes, defined by an HbA1c of 7.5% or below (mean, 6.8%), from 23 European centers (in Sweden, Austria, Germany, Spain, and the Netherlands), randomizing them to wear the Libre or perform self glucose monitoring using finger-stick testing for 6 months. Patients who were already using CGM or sensor-augmented pump therapy were excluded from the study

Well-controlled patients were used, because they would be expected to have higher rates of hypoglycemia, so that the effects of the Libre on this end point could be better detected, Dr Bolinder explained during the poster session.

The primary outcome, change in time from baseline in hypoglycemia (< 3.9 mmol/L [< 70 mg/dL]), was reduced from 3.38 to 2.03 hours per day in the Libre group and from 3.44 to 3.27 in the controls, with a significant difference between the two groups (P < .0001).

That reduction corresponded to 38% less time spent in hypoglycemia per day, seen in both the subgroup of younger patients (aged 18 to 24) and in those aged 25 and older, Dr Bolinder reported during the poster session.

Time spent in hypoglycemia was reduced almost immediately after the patients began viewing the sensor-based results.

"To the best of our knowledge, this is the first randomized controlled trial that has compared the effect of new flash glucose monitoring technology with self-monitoring of blood glucose on hypoglycemia," note Dr Bolinder and colleagues.

The mean number of self-monitored blood glucose tests performed per day by the intervention group dropped from 5.5 to 0.5, while the number of scans per day started at a mean of 18 and dropped slightly to an average 15 by 3 months.

In contrast, the number of finger-stick tests performed in the control group remained about the same, from 5.8 per day at baseline to 5.6 per day at 6 months.

At 6 months, HbA1c levels in the intervention group were essentially unchanged compared with the control group and from baseline.

"Our findings showed that replacing self-monitoring of blood glucose with novel flash sensor-based glucose monitoring demonstrated superior reduction in time in hypoglycemia without deterioration of glycated hemoglobin," the researchers conclude.

Some Sensor-Related Adverse Events Reported

Ten participants in the intervention group experienced 13 adverse events related to wearing the sensor, including four with allergy (one severe, three moderate), one each with mild itching and rash, four with severe insertion-site symptoms, two with erythema (one severe), and one with moderate edema. Seven participants withdrew from the study due to device-related adverse events or repetitive sensor insertion-related symptoms.

Overall, there were five serious adverse events in each study group, including two hypoglycemia serious adverse events (requiring hospitalization or third-party intervention) with Libre vs four in the control group.

Benefit Also Seen With Libre in Type 2 Diabetes

In another poster at the meeting, Dr Thomas Haak, of Diabetes Zentrum Mergentheim, Germany, presented data showing similar outcomes with the FreeStyle Libre Flash system in 139 patients with type 2 diabetes on intensive insulin therapy who had elected to continue using the Libre for a further 6 months following an initial 6-month trial.

In patients under 65 years of age, the Libre reduced hypoglycemia by 0.53 hours per day at 12 months (P = .0262) and in those aged 65 and older by 0.91 hours per day (P = .0019) compared with their baseline readings.

Dr Tack told Medscape Medical News: "It's a whole new thing. We'll see where it goes."

Both studies were funded by Abbott Diabetes Care. Dr Bolinder has received honoraria for consulting or lecture fees from Abbott Diabetes Care, AstraZeneca, Insulet, Integrity Applications, and Sanofi. Disclosures for the coauthors are listed in the article. Dr Hovorka reports grants from JDRF, the National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award; nonfinancial support from Abbott Diabetes Care and Diasend; speaker honoraria from Eli Lilly, Novo Nordisk, Medtronic, and BBraun, serving on advisory panels for Eli Lilly and Novo Nordisk; receiving license fees from BBraun and Medtronic; and serving as a consultant to BBraun; he has patents and patent applications related to closed-loop insulin delivery. He has received support for diabetes technology research from the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, Diabetes UK, Helmsley Trust, National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award. Drs Thabit and Lia declare no relevant financial relationships. Dr Russell has received honoraria from Tandem and Novo Nordisk; lecture and other fees from Tandem, Sanofi, Dexcom, and Eli Lilly; and nonfinancial support from Dexcom, Tandem Diabetes, SweetSpot Diabetes, International Biomedical, Abbott Diabetes Care, Insulet, and Medtronic. He owns stocks/shares in Companion Medical and has patents pending on the bionic pancreas. Dr Haak has no relevant financial relationships. Ms Assardo is an Abbott employee.

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Lancet. Published online September 12, 2016. Abstract, Editorial

European Association for the Study of Diabetes 2016 Annual Meeting. September 15, 2016; Munich, Germany. Abstracts 873, 872.

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