Sensor-augmented insulin-pump therapy with an automated low-glucose suspension feature reduced severe hypoglycemia among patients with type 1 diabetes who have hypoglycemic unawareness, a new study finds.
The device used in the study, the Medtronic Paradigm Veo System, is a combination insulin pump and continuous glucose sensor, in which the pump suspends insulin delivery for up to 2 hours when the sensor detects a glucose level below a prespecified threshold. The Veo has been available in over 50 countries since 2009 but has not yet been cleared by the US Food and Drug Administration.
The new findings, from a 6-month study of 95 patients aged 4 to 20 years with type 1 diabetes and hypoglycemia unawareness, is the first randomized controlled trial to demonstrate a significant reduction in severe hypoglycemia with the use of the low-glucose-suspension feature in such a patient population. The results are published in the September 25 issue of the Journal of the American Medical Association by Trang T. Ly, MBBS, from the Princess Margaret Hospital for Children, Perth, Western Australia, and colleagues.
A larger previous randomized trial published earlier this year, ASPIRE, found significant reductions in nocturnal hypoglycemia with the same device. The current study differs in that it enrolled only patients with hypoglycemia unawareness; it was also longer (6 vs 3 months), and the included patients were younger and had lesser duration of diabetes than in ASPIRE.
In an editorial accompanying the new study, Pratik Choudhary, MBBS, MD, from King's College London, United Kingdom, says that, taken together, the totality of the data from all trials "demonstrates the ability of sensor-augmented insulin pumps with threshold suspension function to provide a significant reduction in severe hypoglycemia.
"These data can now be used to evaluate the health economic benefits of this therapy and also can be used by clinicians, payers, and regulatory authorities to help make this therapy and technology more widely available to patients who struggle daily with hypoglycemia," he adds.
Severe Hypoglycemia Prevented
In the study, 95 patients were randomized by computer to the sensor-augmented pump with low-glucose suspension (n = 46) or to pump-only therapy (n = 49).
Whereas ASPIRE had compared sensor-augmented pump therapy with and without the low-glucose-suspension feature, Dr. Ly and colleagues say they chose pump-only therapy for the control group because it is the more commonly used treatment.
The primary end point of the study was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment).
After 6 months of treatment, the number of primary-end-point events decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose-suspension group (there was a very large imbalance in the baseline rates of severe and moderate hypoglycemia between the groups).
After controlling for baseline hypoglycemia, the researchers found that the adjusted incidence rate per 100 patient-months was 34.2 for the pump-only group compared with 9.5 for the low-glucose-suspension group, giving a significant incidence rate ratio of 3.6 (P < .001) favoring the low-glucose-suspension group.
A separate analysis done just among the 30 patients under 12 years of age also showed a significant adjusted rate ratio for the primary end point of 5.5 ( P < .001) in favor of the low-glucose-suspension therapy.
"Although an exploratory end point, it is notable that there were no seizure or coma episodes in the intervention group, despite these continuing at the same rate in the control group. These findings suggest that automated insulin suspension can reduce the incidence of hypoglycemic events in those most at risk — that is, those with impaired awareness of hypoglycemia," Dr. Ly and colleagues write.
Glycated-hemoglobin levels were similar between the 2 groups at baseline and didn't change over the 6-month study period. There were no episodes of hyperglycemia with ketosis or of diabetic ketoacidosis, something Dr. Choudhary notes is "reassuring."
Hypoglycemia-unawareness scores improved similarly in both groups, with no differences between the low-glucose-suspension and pump-only treatments.
Counterregulatory hormone responses to hypoglycemia were not changed in either group, which is perhaps not surprising, since the low-glucose-suspension technology doesn't eliminate hypoglycemia but merely reduces its magnitude and duration, the authors point out.
Replace Physiologic Awareness With Technological?
In his editorial, Dr. Choudhary notes that the availability of continuous glucose monitoring (CGM) had been expected to reduce hypoglycemic episodes, but trials have mostly shown that not to be the case.
One problem has been the low rates of hypoglycemia in these trials. The current study aimed to overcome this by focusing specifically on patients with hypoglycemic unawareness, which is present in about 30% of all type 1 diabetes patients, who, as a result, are at a 3- to 6-fold greater risk of severe hypoglycemia.
But, he adds, the data have also suggested that patients tend to sleep through CGM alarms and that overall inaccuracy of the systems has contributed to the lack of effect in reducing hypoglycemia.
Dr. Choudhary also pointed out that the relatively young age of the subjects in this study (mean, < 20 years) with relatively short diabetes duration is very different from the majority with hypoglycemic unawareness, who are typically older than 40 years and with more than 25 years of diabetes duration. Results might differ for that population, he noted.
Still, "The possibility of replacing 'physiological awareness' with 'technological awareness' offers an exciting opportunity to help these patients counter the increased risk of severe hypoglycemia and the disruption it causes."
Dr. Ly was supported by a Juvenile Diabetes Research Foundation postdoctoral fellowship and received travel support from Medtronic. Disclosures for the coauthors are listed in the article. Dr. Choudhary reported receiving speaker fees and travel support from Medtronic and having participated in clinical studies funded by Medtronic.
JAMA 2013; 310:1240-47, 1235-1236.
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Cite this: Low-Glucose-Suspension Feature Cuts Severe Hypoglycemia - Medscape - Sep 24, 2013.