Page 258 - Glucose Monitoring Devices

Clinical studies with LGS system 265

study, participants only used CGM with the LGS off and then the LGS feature was
activated for the following 3 weeks. The authors reported a significant reduction in
the duration of nocturnal hypoglycemia with the use of the LGS feature in study
participants who were in the highest quartile of nocturnal hypoglycemia at baseline
(median 46.2 vs. 1.8 min/day, P ¼.02). There was no difference in mean sensor
glucose between the LGS off or LGS on periods. All subjects in that clinical trial
reported that the LGS was useful and 93% reported feeling safer at night. The find-
ings suggested that using an LGS system was safe in reducing the severity of
nocturnal hypoglycemia without an increase in rebound severe hyperglycemia in
patients with T1D [35]. Similar results have been reported in a study from Germany
with data from 21 pediatric patients with T1D using the LGS system. The area under
the curve for sensor glucose <70 mg/dL was reduced from 0.76 to 0.53 and there
was a significant reduction in the duration of hypoglycemia by 43% without any
serious adverse events (ketoacidosis) among these participants with T1D [36]. In
a clinical trial from Australia, 95 patients with T1D (mean age 18.6 years) using
insulin pumps were randomized to receive either a CGM with the LGS feature
(n ¼ 46) or no CGM (n ¼ 49) [37]. After 6 months of treatment, the moderate-
to-severe hypoglycemic event rates decreased from 28 to 16 in the pump-only group
versus 175 to 35 in the low-glucose suspension group [37]. Despite a significant
reduction in moderate-to-severe hypoglycemia among LGS users with T1D, there
was no change in glycated hemoglobin (HbA1c) in the LGS group compared to
insulin pump users. The same group evaluated glucose profiles following 2 h of
full LGS suspensions in 24 patients with T1D who had hypoglycemia unawareness
as defined by a Clarke score of four or greater [38]. There was an improvement in
HbA1c and hypoglycemia awareness scores over 6 months among LGS users with
T1D. There were 126 full 2-h suspend events among these 24 T1D patients with
hypoglycemia unawareness and, as expected, most suspensions happened at night
before 3:00 a.m. All the LGS activations occurred when sensor glucose approached
60 mg/dL and the mean sensor glucose at the end of the 2-h suspend period was
99 6 mg/dL [38]. These data confirmed the effectiveness of LGS systems in
reducing the severity and duration of hypoglycemia in patients with T1D with
impaired hypoglycemia awareness.
Despite the Medtronic Paradigm Veo being safe and effective in preventing the
duration and severity of hypoglycemia, and commercially available in Europe and
other parts of the world since June 2009, it was not approved by the US Food and
Drug Administration (FDA) until September 2013. The first pivotal study in the
United States, the ASPIRE In-Clinic (Automation to Simulate Pancreatic Insulin
Response) was conducted to establish the safety of LGS systems in patients with
T1D [39]. In this study, 55 subjects with T1D aged 17e58 years were randomized
in a cross-over study. Subjects participated in an exercise-induced hypoglycemia
session with the LGS function on or off. LGS was set to suspend insulin delivery
for 2 h once a sensor glucose value of 70 mg/dL or below was detected. There
was a significant reduction in hypoglycemia duration (by 30 min) in LGS-on
sessions compared to LGS-off sessions (138.5 76.68 vs. 170.7 75.91 min,