A novel insulin pump that stops pumping when glucose goes too low reduced serious hypoglycemia episodes in high-risk type 1 diabetes patients, a clinical trial affirmed.
Events requiring assistance for treatment or causing hypoglycemic coma or seizures occurred 3.6-times less often with the glucose-suspend feature on a device looped in with continuous monitoring compared with a standard insulin pump alone, Timothy W. Jones, MBBS, MD, of Princess Margaret Hospital for Children in Perth, Australia, and colleagues found.
That benefit didn't come at the expense of higher overall hemoglobin A1c, nor were there any ketoacidosis- or ketosis-related adverse events, the researchers reported in the Sept. 25 issue of the Journal of the American Medical Association.
"For the patient, a reduction in the risk of a major hypoglycemia event is the most relevant potential benefit of insulin suspension," they pointed out.
Another recent study, ASPIRE, supported that same benefit. It found the sensor-augmented insulin pump reduced nocturnal hypoglycemia and prevented severe events compared with the same device setup without the extra programming.
The trial by Jones and colleagues was a "critically important" addition because it selectively recruited high-risk patients with impaired awareness of hypoglycemia, Pratik Choudhary, MBBS, MD, of King's College London, noted in an accompanying editorial.
Such patients account for roughly 30% in type 1 diabetes and are at three- to six-fold higher risk of severe hypoglycemia.
Restoring that awareness is tough to achieve and even harder to maintain in clinical practice, he explained.
"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," Choudhary wrote.
The trial included 95 patients (ages 4 to 50) randomized to stay on their own standard insulin pump or to receive the Medtronic Paradigm pump with automated suspension of insulin infusion for up to 2 hours when glucose levels reach a preset threshold of 60 mg/dL.
The pump is branded as Veo in Europe, where it is already approved, but is being called 530G for the U.S. market.
The combined rate of moderate and severe hypoglycemia events decreased from 28 in the 6 months prior to baseline to 16 after 6 months of treatment in the pump-only group compared with a drop from 175 to 35 in the low-glucose suspension group.
After adjustment for the baseline hypoglycemia rate, the incidence was lower with the low-glucose suspension feature at 9.5 versus 34.2 events per 100 patient-months with the standard pump, which was a significant difference (P<0.001).
Severe events resulting in hypoglycemic coma or seizure were uncommon but also decreased with the novel feature.
Six occurred in the pump-only group and five in the low-glucose suspension group in the 6 months prior to baseline. But while no further events happened with the protective feature enabled during the 6-month treatment period, another six occurred in the standard group. The 1.5-fold difference was significant (P=0.02).
Low-glucose suspend group patients also spent less total time in the hypoglycemic range through the day and night by both a 70 mg/dL and 60 mg/dL during the intervention period.
Glycated hemoglobin concentrations remained unchanged from baseline in both groups.
The researchers suggested that reductions in moderate hypoglycemia rates in the control group may have been because they altered their behavior and recall while being observed.
The difference between groups in moderate hypoglycemic events lost significance after excluding two outliers, ages 9 and 10.
While Jones and colleagues noted that younger children often have more variability in this measure, it "raises the possibility that the results are due to a chance imbalance rather than representing a true finding."
Other limitations were the big imbalance in baseline hypoglycemic events between groups, which wasn't expected in a randomized trial setting, and possible lack of generalizability to patients with better awareness of hypoglycemia.
Moreover, the trial population may not have been representative of patients with impaired awareness of hypoglycemia either, Choudhary added.
The mean age in the trial was young at 18.6, diabetes duration short at 11 years, and the younger children likely had recall of severe hypoglycemia dependent on parents.
"These demographic features are very different from the majority of patients with impaired awareness of hypoglycemia, who typically are older than 40 years and have more than 25 years of diabetes duration," Choudhary cautioned.
"It is possible that patients with longer duration of diabetes, who may have associated problems such as lipohypertrophy, anti-insulin antibodies, and more entrenched health beliefs that may predispose to severe hypoglycemia may not be able to demonstrate similar reductions in severe hypoglycemia events," he said.
Primary source: Journal of the American Medical Association
Source reference: Ly TT, et al "Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes a randomized clinical trial" JAMA 2013;310:1240-1247.
Additional source: Journal of the American Medical Association
Source reference: Choudhary P "Insulin pump therapy with automated insulin suspension toward freedom from nocturnal hypoglycemia" JAMA 2013;310:1235-1236.