Κεφαλονιά 31/5/2015

Δρ. Αλέξανδρος Καμαράτος Md, Phd

Current situation

The problem

Clinical evidence

Better glycemic control with sensor augmented pump therapy (SAP) vs. MDI

SAP reduces A1C up to 1.2%, without an increase in hypoglycaemia1,2

Significant reduction in glycaemic variability in children3

SAP enables more patients to reach target A1C levels4

SAP therapy has shown to be cost-effective vs pump alone and vs MDI5,6

The VALUE of Insulin Pumps are supported numerous meta-analyses, and 20+ cost-effectiveness publications.

1. Bergenstal RM et al. New England Journal 2010;363(4):311-20 2. Chase, H. Peter, et al. Diabetes Technology & Therapeutics 12.7 (2010): 507-515. 3. Kordonouri O et al. Diabetologia 2010;53(12):2487-95 4. JDFR. N Engl J. 2008 Oct;359(14):1464–76 5. Ly TT et al. Value Health. 2014;17(5):561-9 6. Roze, S. et al., 2014. Diabetic medicine , pp.1–9.

Sensor Augmented Pump (SAP) had greater A1C reduction vs. MDI at 3 months and sustained it over 12 months.1,2

Average A1C reduction for SAP and MDI

Therapies

Current situation

The problem

Clinical evidence

Reducing hypoglycemia is critical for better diabetes care

1. Seaquist ER, et al. J Clin Endocrinol Metab. 2013;98(5):1845-59. 2. Pickup J et al. Diabet Med 2008;25:765-74 3. Misso ML et al. Cochrane Database Syst Rev. 2010;(1):CD005103. 4. Bergenstal RM et al. N

Engl J Med. 2013;369(3):224-32.

• Hypoglycemia (low blood glucose) can cause confusion, disorientation, loss of consciousness, and in the worst cases coma and even death. 1

• Unmet need: CSII and SAP reduce A1C levels (vs. MDI) without increasing hypoglycemia, however effective management of nocturnal and recurrent hypoglycemia calls for a therapy that detects and mitigates severe hypoglycemia.2,3,4

Landscape of Options for Intensive Insulin Therapy

“We know since the DCCT trial that when you try

to improve the metabolic control of type 1 diabetic

patients there is a price to pay, and the price is

hypoglycaemia. And we all know that this is a

huge burden for patients”

Dr Conget, Spain

“Hypoglycaemia is one of the most important

challenge currently. With the pump you can go

lower with your blood sugars and prevent many

high blood sugars but the problem is now the low

side. You want to go low but you want to do it safely.”

- Dr Veeze, Netherlands, Current ISPAD President

Therapies

Current situation

The problem

Clinical evidence

Economic burden of hypoglycemia

DIRECT COSTS

Hospitalizations for severe hypoglycemic episodes are the key cost drivers in the management of diabetic patients without further

complications.1,3

Severe hypoglycemic episode (requiring hospitalization) costs health care systems up to €4,830 in Europe.2

4.4 days of hospitalization per severe hypoglycemic episode (UK)3

INDIRECT COSTS

Patients with hypoglycemia have shown 77% more short-term disabilitydays annually and a 5-fold greater risk of short-term disability the week following a hypoglycemic event.4

Absenteeism following a mild/moderate episode during work ranges from 9.9 hours to 14.7 hours for a nocturnal episode.5

Severe episodes among T1DM patients result in 3.6 days off work on average.6

Curkendall S et al. Endocr Pract 2009 May 1;15(4):302-12. 2. DRG Browser (2013) 3. Leese GP et al. Diabetes Care 2003 Apr 1;26(4):1176-80.

4. Rhoads GG et al. J Occup Environ Med 2005;47(5):447-52. 5. Brod M et al. Value Health 2011;14(5):665-671. 6. Davis RE et al. Curr Med Res Opin 2005;21:1477-1483.

Medical Costs:Average severe episode € 68 2

Hospital Costs:Hypoglycemic Episode with Hospitalization are up to €4,830 in DE2

Indirect Costs:3.6 missed days of work per severe event 6

Therapies

Current situation

The problem

Clinical evidence

Executive summary

CURRENT SITUATION

Reducing and controlling A1C has significant clinical and economic benefits1

Insulin Pump Therapy2 and Sensor Augmented Pump Therapy (SAP) 3

technologies have shown to reduce A1C more effectively compared to MDIand are cost-effective4

The challenges of optimally managing T1DM faced by patients, physicians, and payers can be effectively and economically addressed with MiniMedTM 640G and SmartGuardTM

THE PROBLEM

Hypoglycemia has a significant clinical, economic and human burden5

T1 patients have been shown to have 1 or more severe hypoevents per year leading to significant costs and impairedquality of life. Hypo Prone and hypo-unaware patients will have significantly higher rates6

Reducing hypoglycemia is CRITICAL for better diabetes care

ADVANCED PROTECTION FROM HYPOGLYCEMIA

MiniMedTM 640G with SmartGuardTM

THE CLINICAL EVIDENCE

2 large RCTs have shown reductions in hypoglycemia

1. Rose et al. Diabetes care. 2014 37(1), pp.44–9. 2. Pickup J et al. Diabet Med 2008;25:765-74 3. Bergenstal RM et al. New England Journal 2010;363(4):311-20 4. Roze, S. et al. Diabet Med 2014; pp.1–9 5. Seaquist ER, et al. J Clin Endocrinol Metab. 2013;98(5):1845-59 6. Ly TT et al. Diabetes Care 2012;35(7):1462-1465. 8. Bergenstal RM, et al. N Engl J Med. 2013;369(3):224-32. 9. Ly TT et al. JAMA. 2013;310(12):1240-7.

Therapies

Current situation

The problem

Clinical evidence

MiniMedTM 640G with SmartGuardTM

ADVANCED PROTECTION FROM HYPOGLYCEMIA WITH SMARTGUARD1

Continuous monitoring of sensor glucose levels.

Automatic suspension of insulin delivery when sensor glucose is predicted to approach a low glycemic limit2

Resumption of insulin delivery when sensor glucose levels recover3

1. Bergenstal RM et al. N Engl J Med. 2013;369(3):224-232. 2. Insulin is suspended when sensor glucose is at or within 3.9 mmol/L above the low limit and estimated to be within 1.1 mmol/L above the low limit in 30 minutes AND the pump must not be in the refractory period. 3. Insulin resumes

when sensor glucose is at least 1.1 mmol/L above the low limit and estimated to be more than 2.2 mmol/L above in 30 minutes AND insulin must have been suspended for at least 30 minutes. 4. CCR Study, 2012 HFMD, Inc. Data on file at Medtronic MiniMed, Inc. Northridge, CA. 5. The MiniMed 640G insulin

pump has an IPX8 ratingis waterproof in up to 12 feet of water for 24 hours at a time; The Guardian 2 Link transmitter is waterproof in up to 8 feet of water for up to 30 minutes. See MiniMed 640G or Guardian 2 Link User Guides for a complete description of the waterproof capabilities and proper use

instructions. 6. Compared to Medtronic MiniMed Paradigm™ Veo™ system.

PERSONALIZED CONVENIENCE

Informative Bolus WizardTM

Programmable treatment reminders

Remote bolus from meter

INTUITIVE4, PATIENT-FRIENDLY DESIGN

Full-color, auto-brightness display for easy readability even for patients with reduced eyesight

Waterproof,5 allowing uninterrupted wear

Louder,6 volume-adjustable alerts

Therapies

Internal Use Only

Home Screen

Basal: gives you access to basal insulin options

BG reading: displays a BG taken in the last 12 minutes

Current time

Active insulin: displays any insulin still active from previous boluses Bolus:

gives you access to the bolus delivery screen and other bolus insulin options

Statusbar: provides a quick look at the pump’s status

Internal Use Only

PurposeCan set a temp basal ahead of time for recurring, short term situations

BenefitA more convenient way to use a Temp Basal that is used repeatedly without having to program it each time it is used

Details• Can set up to 8 Preset Temp basal rates

• Temp 1- 4, High Activity, Moderate Activity, Low Activity, Sick• Once set up, Preset Temp appears as an option when Basal is

selected from the Home screen• Review or cancel by selecting Basal (T) on Home screen

Preset Temp Basal

Internal Use Only

PurposeAble to set up in advance bolus deliveries that you expect to use frequently

BenefitAllows common bolus amounts to be pre-programmed

Details: • Can set up to 8: Bolus 1- 4, Breakfast, Lunch, Dinner, Snack• Once set, Preset Bolus appears when Bolus is selected on the Home screen• Can be delivered as Normal, Dual or Square Wave bolus

Preset Bolus Setup

Internal Use Only

PurposeAllows blood glucose readings to be sent directly to the pump

Benefit• High accuracy• Wireless capability eliminates need to manually enter BG readings into pump• Remote bolus capability• Communication device for CareLink• Compact, discreet design

Details

Using the Contour Next / Plus Link 2.4 Meter from Bayer

Menu and Power Button USB Connector

Protective USB Cap

Selection/Scrolling ButtonsDisplay Screen

Test Strip Portand Port Light

Internal Use Only

Trend Arrows or - SG has been rising or falling about 1-2 mmol/L over the last 20 minutes

or - SG has been rising or falling about 2-3 mmol/L over the last 20 minutes

or - SG has been rising or falling greater than 3 mmol/L over the last 20 minutes

Home Screen when Using CGM

Additional Sensor Icons

High Limit3 hr Sensor Glucose (SG) Graph

Low Limit

Most recent SensorGlucose (SG) Reading

Suspend by Sensor Icon

Internal Use Only

Home Screen when Using CGM

Additional Sensor Icons

High Limit

3 hr Sensor Glucose (SG) Graph

Low Limit

Trend Arrows

Most recent SensorGlucose (SG) Reading

Suspend by Sensor Icon

Suspend before low or Suspend on low feature is on and ready.

Suspend feature is on but is unavailable due to a recent suspend or sensor glucose values not available.

Suspend before low or Suspend on low is active. Insulin delivery is stopped.

Internal Use Only

Sensor must first be turned on before alerts can be set.

Sensor Glucose Alerts

CGM Alert Settings

13.9 mmol/L

4.0 mmol/L

Internal Use Only

Purpose: Provides alerts or suspends insulin delivery when sensor glucose values areapproaching or reach the pre-set low limit

Benefit: Helps to minimize low glucose excursions by providing alerts and/or suspending insulin delivery

Details: Up to 8 time segments and low limits can be set per dayOptions per time segment:

• Suspend before low• Alert before low• Suspend on low• Alert on low

Low Settings

Suspend by Sensor: Suspend on Low

minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

0 30 60 90 120

Low Limit

Suspends basal insulin because SG reaches the Low Limit

Internal Use Only

Suspend by Sensor: Suspend on Low

minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

0 30 60 90 120

Low Limit

Alert before low: option to be alerted when SG estimated to reach low limit in 30 minutes

Internal Use Only

Suspend by Sensor: Suspend on Low

minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

0 30 60 90 120

Low Limit

Alert on low: will always alert when Suspend on low occurs

Internal Use Only

Suspend by Sensor: Suspend before Low

minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

3.9 above Low Limit

1.1 above Low Limit

0 30 60 90 120

Low Limit

Suspends basal insulin because SG:• is within 3.9 mmol/L above the Low Limit • AND estimated to be within 1.1 mmol/L above the Low Limit with in 30 min

Internal Use Only

Suspend by Sensor: Suspend before Low

minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

3.9 above Low Limit

1.1 above Low Limit

0 30 60 90 120

Low Limit

Alert before low: option to be alerted when insulin is suspended

Internal Use Only

Suspend by Sensor: Suspend before Low

minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

3.9 above Low Limit

1.1 above Low Limit

0 30 60 90 120

Low Limit

Alert on low: alert will sound if low limit is reached during the suspend.

Internal Use Only

Suspend by Sensor: Auto-resume based on SG

Minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

1.1 above Low Limit

0 30 60 90 120

Low Limit

Resumes basal delivery because:• SG is at least 1.1 mmol/L above Low Limit• AND estimated to be more than 2.2 mmol/L above the Low Limit within 30 min • AND insulin has been suspended for at least 30 min

2.2 above Low Limit

Internal Use Only

Suspend by Sensor: Maximum 2 hour suspend

minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

2.2 above Low Limit

1.1 above Low Limit

0 30 60 90 120

Low Limit

Resumes basal delivery because:• user has not manually resumed insulin• auto resume based on SG criteria has not been met • basal insulin has been suspended for 2 hours

Internal Use Only

Suspend by Sensor: Maximum 2 hour suspend

minutes00:00 01:00 02:00

Sens

or G

luco

se V

alue

2.2 above Low Limit

1.1 above Low Limit

0 30 60 90 120

Low Limit

Alert will always occur when SG is auto resumed after 2 hour maximum suspend

Internal Use Only

HCP PATIENT

Reduction of hypoglycemia with SmartGuard™

− Predictive suspend

− Predictive resume avoiding hyperglycemic rebound

− Multiple low limit setting

Increased patient safety & protection thanks to intelligent pump features:

− Predictive battery end of life

− Self-test

− Bolus progress bar and Stop Bolus

Protection from dangerous highs and lows with SmartGuard™

− Predictive suspend

− Automatic resume when glucose level recover

− Increased protection when needed with multiple low limit setting

Increased safety & protection thanks to intelligent pump features:

− Predictive battery end of life

− Self-test

− Bolus progress bar and Stop Bolus

Messaging guideWhat are the key product messages?

HCP PATIENT

Correct insulin dosing & better patient understanding with Bolus Wizard™

Discretion & ease of use with remote bolusing

Easy therapy customisation with:

− Preset bolus options

− Personalised basal patterns

− Programmable treatment reminders

Simplified insulin dosing with Bolus Wizard™

Simplicity & discretion with linking glucose meter allowing for remote bolusing and uploading of data to CL

Easy tailoring to individual needs with:

− Preset bolus options & personalised basal patterns

− Programmable treatment reminders− Adjustable audio options

Messaging guideWhat are the key product messages?

HCP PATIENT

Easy training thanks to the intuitive screen navigation

Easy readability for all patients with the full-color, auto-brightness display

Uninterrupted wear thanks to the IPX8 waterproof rating

Less button pushing, ease of use thanks to the intuitive screen navigation

Easy readability in all conditions with the full-color, auto-brightness display

Flexibility to enjoy water activities thanks to the IPX8 waterproof rating

Messaging guideWhat are the key product messages?

Current situation

The problem

Clinical evidence

PILGRIM Study demonstrates advanced protection from hypoglycemia with SmartGuardTM technology1

1. Danne T et al. Diabetes Technology & Therapeutics. 2014; 16(6):338:347.

*PLGM (predictive low glucose management) was suspend terminology used in the study and report. Actual brand name is SmartGuard technology.

Single-center observational study of 22 youths (14-20 years) where hypoglycemia was induced by exercise while using SmartGuart technology.* The results show that SmartGuard may further reduce the severity of hypoglycemia.

80% of hypoglycemic events were avoided by use of SmartGuard (defined as SG <70 mg/dL)

SmartGuard achieved 42% less time spent lowcompared to Low Glucose Suspend

Therapies

Current situation

The problem

Clinical evidence

Landmark ASPIRE trial1 showssignificantly less hypoglycemic events*

1. Bergenstal RM et al. N Engl J Med. 2013;369(3):224-32.

Hypoglycemia events*** per patient-week Sensor glucose distribution <70 mg/dL

Hypoglycemia events less frequent in the Low Glucose Suspend Group.**

Fewer SG values in hypoglycemic ranges in the Low Glucose Suspend Group (p<0.001).

*Study Design: Randomized controlled trial of 247 patients lasting 3 months comparing the MiniMed Veo with Low Glucose Suspend off vs. with Low Glucose Suspend on; A1C control was similar in both groups

**Low-glucose insulin-suspend pumps consist of a CSII insulin pump that is linked to CGM and this automatically suspends the basal infusion rate for up to 2 h in the event of CGM-detected hypoglycaemia.

*** A nocturnal hypoglycemic event was defined as sensor glucose values of 65 mg per deciliter (3.6 mmol per liter) or less between 10 p.m. and 8 a.m. for more than 20 consecutive minutes in the absence of a pump interaction (i.e., meter blood glucose entries, carbohydrate entries, and insulin-delivery changes) within 20 minutes, as determined by reviews of data uploaded with the use of Medtronic CareLink Therapy Management Software for Diabetes.

Therapies

Current situation

The problem

Clinical evidence

Landmark ASPIRE1 trial shows reductionin severity and duration of hypoglycemia

1. Bergenstal RM, et al. N Engl J Med. 2013;369(3):224-32.

Reduction in Nocturnal Hypoglycemia Reduction in (Day + Night) Hypoglycemia

37.5% Reduction in severity and duration (AUC) of NH Events in the Low Glucose Suspend Group

31.4% Reduction in severity and duration (AUC) of ALL Events in the Low Glucose Suspend Group

Study Design: Randomized controlled trial of 247 patients lasting 3 months comparing the MiniMed Veo with Low Glucose Suspend* off vs. with Low Glucose Suspend on; A1C control was similar in both groups

*Low-glucose insulin-suspend pumps consist of a CSII insulin pump that is linked to CGM and this automatically suspends the basal infusion rate for up to 2 h in the event of CGM-detected hypoglycaemia.

The Therapies

Current situation

The problem

Clinical evidence

Reduction in severe hypoglycemia events and improved awareness

1. Ly TT et al. JAMA. 2013;310(12):1240-7. 2. McBride M et al. Presented ISPOR 16th. Dublin November 2013. 3. Ly TT et al. Diabetes Care 34: 50 – 52.2011 4. Ly TT et al. Value Health. 2014;17(5):561-9.

Significantly reduced rate of severe hypoglycemic events, defined as seizure or coma1

Significant Improvement in Quality of Life (EQ5D Utility: +0.073 favouring the SAP+LGS group after 6 months, p<0.05)2

CGM resulted in a significantly improved epinephrine response implying improved awareness of hypoglycemia (604% change in CGM group vs 114% change in the standard care group, p=0.048).3

SAP with insulin suspension is considered a cost effective treatment option for hypo-prone patients.4

Study Design: Randomized Control Trial over 6 months, n = 95 (children & adults with impaired hypo awareness); 2 groups: MiniMed VEO SAP with LGS ON vs CSII alone

Therapies0 Severe Hypo Events (coma or seizure)1

Κεφαλονιά 31/5/2015