hypo protection plan

1. Pump and CGM Clinical Data: the ASPIRE
In-Home Study

2. Course Objectives
This module shall empower you to:

Understand the ASPIRE In-Home Study objective, study design and results

Understand the ASPIRE In-Home conclusions and how they can be applied
in everyday clinical practice

3. The ASPIRE In-Home Study
The ASPIRE In-Home Study was published electronically ahead of print in
the New England Journal of Medicine (June 2013)
3 | MDT Confidential and Proprietary; Do Not Copy or Distribute
Bergenstal RM, Klonoff DC, Garg SK. E t al. N Engl J Med. June 22, 2013DOI: 10.1056 / NEJMoa1303576.

4. WHY IS IT IMPORTANT ?
Hypoglycaemia is a major burden for many patients
• Hypoglycaemia is a major barrier for patients to achieve good glucose control.
• Hypoglycaemia can have severe consequences for patients (hospitalization) and does
affect their quality of life
• Fear of hypoglycaemia can affect adherence to therapy and lead to hyperglycaemia
VEO + LGS is now clinically proven to significantly reduce hypoglycaemia versus SAP
alone
• There is good evidence that Pump therapy and SAP help reduce exposure to
hypoglycaemia versus MDI.
• ASPIRE In-Home study now provides evidence that the Low Glucose Suspend (LGS)
feature of MiniMed VEO offers the potential to mitigate the risk of hypoglycaemia (number
of events, duration and severity) versus SAP alone.
ASPIRE In-Home : study primary outcome
• The main objective of the ASPIRE In-Home Study is to evaluate the effect of
MiniMed VEO with LGS activated vs. Sensor Augmented Pump (SAP) therapy on
nocturnal hypoglycaemia and HbA1c in patients who experience nocturnal hypos.

5. The objective of ASPIRE In-Home Study
The main objective of the study is to evaluate the effect of VEO + LGS versus SAP on:
- nocturnal hypoglycaemia : “Is LGS effective at reducing hypo”?
- and HbA1c : “Is LGS safe?”
in patients who experience nocturnal hypos ( a ‘hypo-prone’ population)

6. Research & Study Design….
A randomised controlled multicenter parallel study
 Randomized, controlled multicenter trial over a 3 month period: comparing how glucose
control is when the patient has the LGS ON compared to when a subject has only sensor ON
 There was a pre-study period to assess if subjects experienced nocturnal hypoglycaemia
 Patients were randomized to one of 2 treatment paths: :
– Those who have the sensor ON for 3 months and activate the LGS feature.
– Those who have the sensor ON for 3 months without the LGS feature
HbA1c was measured and glycaemic parameters were collected
Patient population included:
– 247 adults and teens (aged 16-70 years) with Type 1 diabetes in 19 centers in the USA.

7. Research & Study Design….
 The Run-In phase was performed to ensure
that the study population was experiencing
night-time hypoglycaemia
 The two randomised arms were well matched
for age, duration of diabetes and HbA1c.

8. RESULTS – EFFICACY OF LGS
LGS reduces the duration and severity (AUC) of hypos
The mean area under the curve
(AUC) can be used to represent the
duration and severity of
hypoglycaemia.
Nocturnal
Mean AUC
(mg/dL*min)
38%
reduction, p<0.01
1600
Results of the ASPIRE In-Home Study
show that:
- Nocturnal hypoglycaemia
represented as Mean Area Under the
Curve (AUC) was significantly
reduced by 38% when LGS was used
1400
1200
1000
800
600
- 24 hours AUC was also significantly
reduced
400
200
0
LGS ON
Baseline
SAP
Study

9. RESULTS – EFFICACY OF LGS
LGS reduces the frequency of hypo events at night
The use of LGS reduced the
frequency of nocturnal
hypoglycaemia events
-
There was 31.8%
decrease in the hypo
events when LGS was
used during the night

10. RESULTS – EFFICACY OF LGS
reduces the frequency of hypo events throughout the full 24 hours.
The study protocol dictated that subjects had to use LGS during the overnight
period. However subjects were encouraged to use LGS during the day.
-
Even though many
patients are more able
to respond to their
symptoms during the
day; there was still a
significant reduction in
the frequency of hypo
events.
LGS reduces the number of hypoglycaemia events
# Hypo events
6
per
patient-week
5
32% reduction
p<0.01
30% reduction
p<0.01
4
3
2
-
There was 30% decrease
in the hypo events when
LGS was used during the
full 24 hours.
1
Baseline
Study
-
0
LGS ON
SAP
NIGHT TIME
LGS ON
SAP
Strictly Confidential | 10
DAY + NIGHT

11. RESULTS – EFFICACY OF LGS
LGS reduces mild, moderate and severe hypos
The LGS threshold was set to
70 mg/dl for the study.
However, minimizing time in
the hypo range also resulted
in a reduction of the number
of values in the more ‘severe’
hypo ranges, those values
below 60mg/dl and below 50
mg/dl.

12. RESULTS – SAFETY OF LGS
LGS did not cause any significant rebound hyperglycaemia

13. RESULTS – SAFETY OF LGS
LGS does not cause HbA1c increase
Use of the LGS feature, and the repeated stopping of insulin during hypo
events cause any deterioration of the HbA1c over the 3 month period.
Glucose measurements 4 hours after LGS activation were still within
acceptable targets.
LGS Active
Glucose (mean±SD )
2h post-suspend (at
insulin resume
92.6 ± 40.7 mg/dL
2h post-resume (4h
after LGS enabled)
168.8 ± 64.6 mg/dL.
There were no severe hypo events in the LGS group, but there were 4 events in the control
group. Neither group reported any DKA events.

14. CONCLUSION – WHAT’S IN IT FOR THE HCPs?
 Patients who experience hypoglycaemia can significantly reduce their
hypoglycemia, safely, without increasing HbA1c levels.
 Use of the LGS feature reduced the weekly rate of hypoglycemic events, suggesting
that it prevented hypoglycemia.
 Automating insulin delivery, using sensor-augmented pump therapy is an
important strategy to reduce hypoglycaemia.

15. Why are these results important?
Hypoglycemia causes significant clinical and economic burden to the health care
system. From a clinical perspective, hypoglycemic episodes can lead to a vicious cycle
of recurrent hypoglycemia which increases the risk of severe hypoglycemia and the
development of hypoglycemia unawareness and hypoglycemia-associated autonomic
failure (HAAF).
Avoiding hypoglycemia can improve one’s awareness of (and may help avoid) future
hypoglycemia.
The ASPIRE-In Home study proves that MiniMed sensor integrated pump system with
automated suspension can reduce hypoglycemia and be an important solution in
reducing the clinical and economic burden associated with hypoglycemia.