This randomized controlled trial, designed to evaluate the effect of continuous glucose monitoring on hypoglycemia in type 1 diabetes, demonstrated a significant reduction by half in time spent in hypoglycemia in relatively well-controlled children and adults with type 1 diabetes. Notably, this finding was paralleled by a significant decrease in HbA1c
, contrary to the results in the Diabetes Control and Complication Trial (DCCT) study where the rate of hypoglycemia increased considerably with lower HbA1c
In the Juvenile Diabetes Research Foundation (JDRF) trial in children and adults with HbA1c
<7% at randomization (15
), hypoglycemia below 60 mg/dL was less pronounced in the continuous monitoring group than in the control group at the end of 6 months (median 18 vs. 35 min/day, P
= 0.05). Moreover, combined outcomes of hypoglycemia and HbA1c
were significantly better in the continuous glucose monitoring patients than in the control patients, which corroborate our findings.
A recent randomized controlled trial named Sensor-Augmented Pump Therapy for A1C Reduction 3 (STAR 3) comparing sensor-augmented pump therapy with multiple-injection therapy demonstrated a significant reduction of HbA1c
in adults and children without an increase in hypoglycemia (22
). However, the area under the curve <70 mg/dL and <50 mg/dL did not differ between the two treatment modalities. It is possible that the relatively small amount of continuous sensor data in the multiple-injection therapy group lacked sufficient power to show a difference. Additionally, the baseline HbA1c
was considerably higher in the STAR 3 trial as compared with the current study.
None of the participants or parents in the current study reported an event of severe hypoglycemia. Similarly, severe hypoglycemia episodes were infrequent in the JDRF trial (less than 10% of the patients) (15
) and the STAR 3 trial (around 13 per 100 patient-years) (22
) and did not differ between the study groups. Neither the JDRF trial nor ours was powered to detect differences in the rate of severe hypoglycemic episodes. In the open extension phase of the JDRF trial, episodes of severe hypoglycemia decreased by almost 50% in the control patients after they were switched to continuous glucose monitoring, but this was not statistically significant (P
= 0.08) (16
Although the number of hypoglycemic excursions below 55 mg/dL was not significantly different between the two groups per 24 h, it was significantly lower in the continuous monitoring group during the night. In the JDRF trial, a higher incidence of nocturnal hypoglycemia is associated with lower HbA1c
in the continuous glucose monitoring group; however, no comparison is made with the control group (23
). Taken together, previous and present data may suggest that the risk of hypoglycemia is alleviated by continuous glucose monitoring. Clinically more meaningful reduction of hypoglycemic events remains to be demonstrated.
Several studies have demonstrated that the use of continuous monitoring above 70% of the time is associated with significantly increased benefit and with a significant lowering of HbA1c
in all age groups (17
). Compliance with the sensor wear in the current study in the continuous monitoring group was more than 6 days per week (86%) and did not decrease significantly with time, with an average of around 5.8 days/week (84%) at the end of the 26-week period (Supplementary Fig. 2B
). This is roughly similar to the adult group and considerably more than the adolescent or children group of the JDRF trial (16
This study protocol stated that the control group should wear a masked sensor for 5 days every second week, amounting to 65 days or around 9 weeks during the 26-week study period. In fact, compliance with the sensor wear in the control group was lower than intended (around 80%). However, when compared with previous studies, the amount of masked continuous monitoring data from the control group was substantial. Combined with the high compliance of sensor use in the continuous monitoring group, this contributed to the power of the statistical analysis.
Our results must be interpreted with caution since the patients and their families were highly motivated, demonstrating good metabolic control with an average of more than five blood glucose measurements per day before randomization, and all three participating centers were academic with high penetration of diabetes-related technology. Additionally, because of its nature, the intervention could not be blinded, rendering the results less compelling. The results may therefore not be simply generalized, and further studies are needed to evaluate the hypoglycemia-preventive effects of continuous glucose monitoring in less well-controlled and less motivated patient populations.
In conclusion, the results of the current study demonstrated significantly shorter time spent in hypoglycemia in children and adults with type 1 diabetes who used continuous glucose monitoring compared with standard SMBG, with a concomitant significant decrease of HbA1c.