Sensor-augmented therapy can diminish hypoglycemia with the low-glucose suspend feature.
To minimize the risk of hypoglycemia, the threshold-suspend feature of sensor-augmented insulin pumps was designed to interrupt insulin delivery at a preset sensor glucose value. This study used the Medtronic Paradigm Veo pump for the interventional group. The pump has a low-glucose suspend feature that allows suspension of insulin delivery for up to 2 hours at a sensor glucose value that does not need confirmation by the person using the pump.
This study from the New England Journal of Medicine was a randomized, controlled, multicenter, open-label trial called the Automation to Stimulate Pancreas Insulin Response (ASPIRE) In-Home study. The objective of the study was to evaluate the effects of the threshold-suspend feature with sensor-augmented insulin-pump therapy, as compared with sensor-augmented insulin-pump therapy alone, on HbA1c levels and nocturnal hypoglycemia.
The patients included in this study were ages 16 to 70 years old and had type 1 diabetes for at least 2 years, had an HbA1c level of 5.8 to 10.0%, and had used insulin-pump therapy for more than six months prior to the study.
There was a 2-week run-in phase, which was repeated and a 3-month study phase. In the run-in phase, patients used Paradigm Revel 2.0 insulin pump and Enlite glucose sensors. For patients to be eligible for randomization, patients wore sensors for at least 80% of the time and had at least two nocturnal hypoglycemic events during the run-in phase.
There were 320 patients who entered the run-in phase, but 73 did not undergo randomization. 247 patients were randomly assigned to sensor-augmented insulin pump therapy with threshold-suspend feature (121 patients) or the control group of standard sensor-augmented insulin pump therapy (126 patients).
The threshold-suspend group used the Paradigm Veo insulin pump; the threshold-suspend feature was set to suspend insulin delivery at glucose values of 70 mg/dL or less, after which the setting ranged from 70 mg/ dL to 90 mg/dL. Between the hours of 10 p.m. and 8 a.m., the threshold-suspend group was instructed to have the suspend feature on. The control group used the Paradigm Revel 2.0 insulin pump with no threshold-suspend feature.
The study looked at a primary safety endpoint of a change in the HbA1c from baseline to the end of the study. The primary efficacy endpoint was the area under the curve (AUC) for nocturnal hypoglycemic events between 10 p.m. and 8 a.m. The secondary endpoints were percentage of sensor glucose values less than 70 mg/dL, rate of hypoglycemic events, characteristics of automatic pump-suspension events and quality-of-life and treatment-related measures.
The study found that there was a significant reduction in the mean AUC for nocturnal hypoglycemia in the threshold-suspend group with 37.5% less than the control group. The mean sensor glucose value was 62.6 mg/dL at the beginning of the nocturnal hypoglycemic events in both groups and at 4 hours it was 162.3 mg/dL in the threshold-suspend group versus 140.0 mg/dL in the control group. The mean AUC of the combined daytime and nighttime hypoglycemic events was 31.4% lower in the threshold-suspend group compared to the control group. They also found that the threshold-suspend group had significantly lower weekly rates of both daytime and nighttime hypoglycemic events compared to the control group.
This study showed that using the threshold-suspend feature could significantly reduce the AUC for nocturnal hypoglycemic events, the weekly rate of nighttime hypoglycemic events and the percentage of nocturnal time spent with sensor glucose values in the hypoglycemic range. Use of the threshold-suspend feature reduced weekly rates of hypoglycemic events and ultimately prevented hypoglycemia. Severe hypoglycemia did not occur in the threshold-suspend group and four of the severe hypoglycemia events happened in the control group at a rate of 0.13 per patient-year.
The study did have some limitations. The sensor glucose values were used for all analyses without validation from another reference method. Runs of sensor glucose values of 65 mg/dL or less lasting less than 20 minutes and those with evidence of a pump interaction were not analyzed. It was thought if they had been included, that the weekly rate of hypoglycemic events would have increased and the mean AUC would have been lower. The generalizability of the study results is minimal because only hypoglycemia-prone patients were included. Lastly, the duration of the study was only 3 months.
Overall, over a 3-month period of the use of the threshold-suspend feature in automatic insulin pumps, it was determined that they can help reduce episodes of hypoglycemia, especially overnight, without any increase in HbA1c. These findings can be useful for people with diabetes who suffer from uncontrolled hypoglycemic events and can help them have better quality of life on automatic insulin pumps.
- Sensor-augmented insulin pump therapy with the threshold-suspend feature can prevent hypoglycemia, especially nocturnal hypoglycemia.
- The mean AUC for nocturnal hypoglycemic events was 37.5% lower in the threshold-suspend group than in the control group.
- Nocturnal hypoglycemic events occurred 31.8% less frequently in the threshold-suspend group.
Bergenstal RM, Klonoff DC, Garg SK, et al. Threshold-based insulin pump interruption for reduction of hypoglycemia. N Engl J Med 2013; 369:224-232.
Jessica Quach, Doctor of Pharmacy Candidate 2018, GA-PCOM School of Pharmacy