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

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 | MDT Confidential and Proprietary; Do Not Copy or Distribute

The ASPIRE In-Home StudyThe ASPIRE In-Home Study was published electronically ahead of print in

the New England Journal of Medicine (June 2013)

Bergenstal RM, Klonoff DC, Garg SK. E t al. N Engl J Med. June 22, 2013DOI: 10.1056 / NEJMoa1303576.

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.

WHY IS IT IMPORTANT ?

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)

The objective of ASPIRE In-Home 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.

Research & Study Design….A randomised controlled multicenter parallel study

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.

Research & Study Design….

The mean area under the curve (AUC) can be used to represent the duration and severity of hypoglycaemia.

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

- 24 hours AUC was also significantly reduced

RESULTS – EFFICACY OF LGSLGS reduces the duration and severity (AUC) of hypos

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LGS ON SAP

Nocturnal Mean AUC

(mg/dL*min)

Baseline Study

38% reduction, p<0.01

RESULTS – EFFICACY OF LGSLGS 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

The study protocol dictated that subjects had to use LGS during the overnight period. However subjects were encouraged to use LGS during the day.

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LGS ON SAP LGS ON SAP

# Hypo eventsper

patient-week

LGS reduces the number of hypoglycaemia events

Baseline

Study

NIGHT TIME DAY + NIGHT

30% reductionp<0.01

32% reductionp<0.01

- 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.

- There was 30% decrease in the hypo events when LGS was used during the full 24 hours.

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RESULTS – EFFICACY OF LGSreduces the frequency of hypo events throughout the full 24 hours.

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.

RESULTS – EFFICACY OF LGSLGS reduces mild, moderate and severe hypos

RESULTS – SAFETY OF LGSLGS did not cause any significant rebound hyperglycaemia

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.

RESULTS – SAFETY OF LGSLGS does not cause HbA1c increase

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.

CONCLUSION – WHAT’S IN IT FOR THE HCPs?

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.