Insulin pump therapy. Healthy Living with Diabetes

Transcription

1 Insulin pump therapy Healthy Living with Diabetes 1

2 AGENDA Why Insulin Pump Therapy Pump Therapy Overview Benefits of Pump Therapy Getting Started on Pump Therapy 2

3 WHY INSULIN PUMP THERAPY UMPWHY INSULIN PUMP Pump therapy offers a safe, effective, convenient, flexible, and discrete, method of delivering insulin. 3

4 PUMP WEAR GALLERY UMPWHY INSULIN PUMP Insulin pump therapy provides more flexibility for patient s lifestyle while giving greater control of their diabetes 4

5 AGENDA Why Insulin Pump Therapy Pump Therapy Overview Benefits of Pump Therapy Getting Started on Pump Therapy 5

6 Benefits of Pump Therapy Insulin Reproducibility Precise & Predictable Delivery Bolus Wizard & Flexibility 6

7 7 AACE/ACE COMPREHENSIVE DIABETES MANAGEMENT ALGORITHM 2015

8 Insulin Reproducibility Clinical Article Review Scholtz- Pharmacokinetic and glucodynamic variability: assessment of insulin glargine, NPH insulin and insulin ultralente in healthy volunteers using a euglycaemic clamp. Pharmacodynamics Variability in Insulin Action* 8

9 Insulin Reproducibility The Problem with Injections Regimented lifestyle: unrealistic Long-acting insulin A large depot, with wide variations in the timing and amount actually absorbed into the blood stream Cannot match varying basal needs (e.g., dawn phenomenon) Insulin Profiles Porcellati F, et al. Diab Care. 2007;30(10):

10 Precise & Predictable Delivery Basal Insulin Delivers continuously/automatically Adjusted to match patient s hepatic glucose production - Between meals and during the night (nocturnal) Similar to a normal functioning pancreas - Maintains BG stability 10

11 Precise & Predictable Delivery Basal Rate Continuous Delivery Advantages: Very precise exact delivery Eliminates large depots Greatly reduces risk of lows Basal Rate u/hr u/hr u/hr 11

12 12-1a 2-3a 4-5a 6-7a 8-9a 10-11a 12-1p 2-3p 4-5p 6-7p 8-9p 10-11p units/hour Precise & Predictable Delivery Basal Insulin Needs Vary Throughout the Day age 3-10 age age age > hour Results indicate it is not reasonable to expect insulin needs to be met by a flat rate of insulin delivery for 24 hours. Scheiner, Gary; Boyer, Bret A. Characteristics of basal insulin requirements by age and gender in Type-1 diabetes patients using insulin pump therapy. Diab Res and Clin Prac, 69 (2005) pg

13 Bolus Wizard & Flexibility ADVANTAGES OF BOLUS WIZARD FEATURE 1. Calculates Meal and Correction Boluses: BG ICR ISF Target Range Benefit: Determines each bolus amount based on patient s individual pump settings & current needs (BG, carb intake, active insulin) 2. Keeps accurate records: Times and values of all BG readings Carbohydrate intake Type, amount, time of boluses Benefit: Provides comprehensive records for therapy evaluation 3. Tracks Active Insulin: Subtracts active insulin from insulin calculated to correct a high, before suggesting total correction amount to take. Benefit: Helps prevent insulin stacking & lows that occur from over correcting when active insulin remains from previous boluses 13

14 Insulin Efficacy of Insulin Pump vs. MDI MDI Injection Injection Injection Injection Normal Insulin Secretion Rapid-acting Insulin Lantus Insulin Pump 0 hr 12 hrs 24 hrs Normal Insulin Secretion Insulin Pump Delivery 14

15 A1C (%) Efficacy of Insulin Pump vs. MDI Pumps Achieve Significant A1C Improvement Metabolic Control (A1C) MDI 8.1% Pump 7.2% 6 Baseline Weeks Doyle, E. A. (2004). A Randomized, Prospective Trial Comparing the Efficacy of Continuous Subcutaneous Insulin Infusion with Multiple Daily Injections Using Insulin Glargine/. Diabetes Care. 27:

16 Efficacy of Insulin Pump vs. MDI CSII REDUCES INCIDENTS OF SEVERE HYPOGLYCEMIA Rudolph JW, Hirsch IB. Endocrine Practice. 2002; 8: Bode,BW, Steed RD, Davidson PC. Diabetes Care. 1996;19:324-7; Boland EA, Grey M, Oesterle A, et al. Diabetes Care. 1999; 22: ; 16

17 17 Efficacy of Insulin Pump vs. MDI

18 Getting Started on Pump Therapy 18

19 INSULIN PUMP SETTINGS Determined by using patient history & clinical judgment Calculated by using standard formulas 19

20 CALCULATE PUMP TDD Reduced Dose Based on daily injection dose Injection Dose X 0.75 Laura s Weight: 70kg 53 units x 0.75 = 40 units/day 70kg x 0.5units = 35 units/day Laura s Pump TDD:( 40 units/day + 35 units/day ) 2 = 37.5 units/day 20

21 21 INSULIN PUMP SETTINGS

22 INSULIN PUMP SETTINGS Total amount of basal insulin delivered over 24 hours Typically ~40-50% of TDD is basal Total amount of bolus insulin given for food & correction in 24 hours Typically ~ 50-60% of TDD is bolus Food Correction 22 22

23 INSULIN PUMP SETTINGS Basal Breakfas t and Bolus Lunch Dinner Snack 12am 3am 6am 9am Noon 3pm 6pm 9pm 11pm 23 23

24 24 INSULIN PUMP SETTINGS

25 BASAL RATE (BR) Basal Rate Total Daily Basal 24 hours Laura s Total Daily Basal Dose: units/day units/day 24 hrs = 0.78 units/hr (Total Daily Basal) Pump Delivers Basal in 0.05 units Starting Basal Rate = 0.75 units/hr or 0.80 units/hr 25

26 26 INSULIN PUMP SETTINGS

27 INSULIN-TO-CARBOHYDRATE RATIO (ICR) Insulin-to-Carb Ratio (Method 1) Daily Carbohydrate Intake Carb grams Total Daily Bolus Insulin-to-Carb Ratio (Method 2) 500 Rule 500 Pump TDD Laura s Total Daily Bolus units/day Laura s Total Daily Dose 37.5 units/day Estimated Daily Carbs ~ 225 grams 225 g u/day = 12 grams/unit (Carb Ratio) u/day = 13 grams/unit (Carb Ratio) 1 unit covers ~ 12 grams 1 unit covers ~ 12 grams 27

28 28 INSULIN PUMP SETTINGS

29 INSULIN SENSITIVITY FACTOR (ISF) Insulin Sensitivity Factor (Method 1) 1800 Rule 1800 Pump Total Daily Dose Laura s Total Daily Dose 37.5 units/day units/day = 48 mg/l 1 unit decreases BG ~ 48 mg/l The number of mg/l one unit of insulin lowers glucose. 29

30 INSULIN PUMP SETTINGS Bolus Wizard Settings 30

31 HOW DOES IT WORK = Insulin Pump Therapy Change reservoir and infusion set every 2 to 3 days 31

32 HOW DOES IT WORK MiniMed Paradigm Insulin Pump Technology REAL-Time Continuous Glucose Monitoring Technology** The MiniMed Paradigm REAL-Time System 32

33 MEDTRONIC DIABETES UPDATES ON CONTINUOUS GLUCOSE MONITORING & INSULIN PUMP Kulvadee A. Sales manager diabetes care

34 Medtronic Diabetes Products i-port Advance 1) Easier onboarding of insulin/ subcutaneous injections 2) Suitable for all ages ipro2 CGM 1) Diagnostic tool that reveals a patient s true glycemic pattern 2) Can be widely used Insulin Pump Therapy 1) Proven therapy when MDI is not suitable 2) Most physiological method of insulin delivery available Pag e 34

35 I-PORT ADVANCE Page 35

36 MEDTRONIC DIABETES TECHNOLOGY PROFESSIONAL CONTINUOUS GLUCOSE MONITORING INSULIN PUMP THERAPY REAL TIME CONTINUOUS GLUCOSE MONITORING CARELINK SYSTEMS 36

37 2 Categories of CGM Professional CGM Owned by clinicians Short term use on patients (6 days) Blind evaluation Retrospective data analyzed by clinician Minimal training required Personal CGM Owned by patients On-going use by patients Displays glucose values and alarms Continuously updated data viewed by patients Requires patient education ipro 2 Paradigm or Minimed 640G System 37

38 WHAT S A GLUCOSE SENSOR AND HOW DOES CGM WORK? TECHNOLOGY BEHIND CONTINUOUS GLUCOSE SENSING

39 KEY CONCEPT: BLOOD GLUCOSE VS. SENSOR GLUCOSE Blood Glucose (BG) is measured in blood Sensor Glucose (SG) is measured in interstitial fluid Sensor glucose correlates well with capillary glucose, when glucose levels are stable 39

40 THE GLUCOSE SENSOR CONSISTS OF 3 LAYERS Semi Permeable Membrane Selective to glucose and oxygen Enzyme The membrane surrounds a glucose oxidase enzyme Electrode 40

41 1 Glucose and Oxygen Enter Membrane When the glucose and oxygen come in contact with the glucose oxidase enzyme, the first chemical reaction takes place Glucose and Oxygen Membrane Enzyme Electrode 41

42 2 First Chemical Reaction Glucose and oxygen come in contact with the glucose oxidase enzyme Glucose and oxygen are converted into Hydrogen Peroxide (H 2 O 2 ) and gluconic acid Membrane Enzyme Glucose and Oxygen H Gly Acid 2 O 2 Electrode 42

43 3 Second Chemical Reaction H 2 O 2 seeps through to the Electrode layer A voltage is applied to the Electrode, causing H 2 O 2 to breakdown into: Hydrogen Oxygen 2 electrons Membrane Enzyme Electrode H 2 O 2 2e- The more glucose in your body, the more H 2 O 2 generated. The more H 2 O 2, the more current generated. 43

44 CONVERTING ISIG TO A GLUCOSE SENSOR VALUE THE GLUCOSE OXIDASE REACTION The 2 electrons generate a current called ISIG ISIG is converted to a sensor glucose value when a BG meter value is entered for calibration Membrane Enzyme Electrode 2e- ISIG The ISIG is Proportional to Glucose Concentration 44

45 Page 45 WHY CGM? RATIONALE BEHIND CGM

46 RECOMMENDATION FROM AACE Continuous glucose monitoring (CGM) should be considered for patients with T1D and T2D on basal-bolus therapy to improve A1C levels and reduce hypoglycemia. Early reports suggest that even patients not taking insulin may benefit from CGM -- AACE Consensus Statement on CGM

47 CGM Provides Visual Feedback of Glucose Control Glycemic Variability CGM provides visual feedback to help patients and clinicians understand glucose variability A1C 9 A1c = 9 in both patients Profiles are very different A1C 9 47

48 A BOAT WITH NO CONTEXT 48

49 The Boat Is Moving Toward Waterfall WITH A MORE COMPLETE PICTURE SEE THE POTENTIAL RISK AND DANGER 49

50 50 WITH A MORE COMPLETE PICTURE, ONE CAN PREVENT POTENTIAL PROBLEMS AND MOVE AWAY FROM DANGER

51 3 CORE GLUCOSE TECHNOLOGIES: CGM - Complimentary and Essential Fingerstick Testing A1C CGM Advanced diabetes management requires comprehensive understanding of glucose control 51

52 CGMS IN DIAGNOSTIC CENTER Consultation in clinic Assessment of patient who requires close glucose monitoring Patients directed to Diagnostic centers for starting of CGMS study Patients goes home and resume normal activities for 6 days Reports can be ed to doctors or hardcopy printed for patient to bring to doctor for review and filed with patient records Patients returns to diagnostic center for download of CGMS data after 6 days 52

53 BENEFITS OF PROFESSIONAL CGM CGM shows the whole picture, not just snapshots of glucose levels. It provides insight into glucose trends between fingersticks, leading to improved knowledge and improved glucose control Reveals true glycaemic patterns, without patient intervention, for clinicians Identifies glucose behaviour throughout the day in response to food, exercise, medications, stress and lifestyle Reinforces daily diabetes management Three easy to read graphs 53

54 REPORTS & INTERPRETATION

55 MEDTRONIC CARELINK IPRO REPORTS: Three are generated automatically Daily Overlay (1 page) Daily Summary (2 pages) Overlay by Meal (2 pages) Page 55

56 REPORT #1: DAILY OVERLAY Summary of the study Highlights the highs and lows of a patient s glucose levels Allows for quick identification of recurring patterns 56

57 DAILY OVERLAY REPORT 57

58 DAILY OVERLAY REPORT 58

59 CASE STUDY 1: NOCTURNAL HYPOGLYCEMIA Physician reports were revealed with Professional CGM Physician Report Nocturnal Hypoglycemia > Daily 59

60 DAILY OVERLAY REPORT - HOW TO USE THE PIE CHARTS Overall, they are spending 55% above 7.8 mmol/l This means: 24 hours X 55% = 13.2 hours per day above target Is this good control? 60

61 REPORT #2: DAILY SUMMARY Shows a breakdown of daily glucose levels Provides further insights into a patient s glucose trends based on their activities 61

62 REPORT #3: MEAL OVERLAY Analyses a patient s pre and post meal glucose levels Allows for an overview of pre and post meal highs and lows. 62

63 PATIENT SELECTION FOR PROFESSIONAL CGM AACE Guidelines for Candidate Selection Patients with type 1 or type 2 diabetes who: are not at their A1C target have recurrent hypoglycemia or hypo unawareness Pregnant women with: Type 1 diabetes Type 2 Gestational diabetes requiring insulin * AACE CGM Task Force. Statement by the American Association of Clinical Endocrinologists Consensus Panel on Continuous Glucose Monitoring. Endocrine Practice. 2010; 16(5):

64 PROFESSIONAL CGM TYPICAL CASES IN PRACTICE Uncontrolled DM Type 2 on oral agent with A1C 7.2-8% Patient does not check glucose regularly or bring in meter or diary I want to better identify what is the primary contributor for patient not at goal Diary has inconsistent glucose readings On basal insulin where should I add prandial insulin? Type 1 patient MDI or insulin pump (without CGM) 64

65 STARTING ON PUMP THERAPY TYPE 2

66 66

67 67

68 68

69 69

70 CARELINK PRO SOFTWARE FOR PARADIGM REAL-TIME CGM

71 CHALLENGES OF DIABETES MANAGEMENT Limited time to spend with patients Complex patient issues Difficulty obtaining precise, accurate information Ineffective time reviewing data in multiple of formats Many logbook formats Different software for every meter 71

72 MEDTRONIC CARELINK INTERFACE PATIENT S HOME PRACTICE/CLINIC Internet Device upload Reports Device upload (if needed) Reports

73 THE 5 MEDTRONIC CARELINK PRO REPORTS Adherence Sensor & Meter Overview Logbook Daily Detail Pump Settings 73

74 ADHERENCE REPORT Monitoring Information Bolus Information Reservoir + Set Information Suspend Information 74

75 Hyperglycaemia: Darker color indicates frequent occurrence Hypoglycaemia Target Range Overnight Breakfast Lunch Dinner 75

76 Plots Patient s Meter BGs Indicates Day s Average BG Target Range Target Range Overnight Breakfast Lunch Dinner Statistical Data Avg BG Number of highs Number of lows Avg carb intake Avg Total Daily Insulin Basal Bolus 76

77 Daily detail no sensor Shows BGs, Insulin delivery, Carbohydrate consumed Daily detail with sensor Shows SG trace, BGs, Insulin delivery, Carbohydrate consumed Sensor trace over consecutive days 77

78 Overnight Low Post Breakfast and Lunch High Details on each bolus Statistical information for day and reporting period 78

79 LOGBOOK REPORT Overnight Breakfast Pre-Lunch Lunch Pre-Dinner Dinner Highs Grams of Carb Lows 79

80 DEVICE SETTINGS REPORT Basal rate information Bolus information Sensor information Use as progress note to document changes in therapy and file in patient s chart Utilities information 80

81 QUESTIONS? THANK YOU Lunch Break

82 DCCT: Treating to target is important in type 1 patients DCCT showed reduction in complications in type 1 patients with 2% reduction in A1C Retinopathy risk* Microalbuminuria + Albuminuria+ Risk of any CV Event** Non-fatal MI, Stroke or CV Death** Clinical neuropathy+ 76% 39% 54% 42% 57% 60% DCCT, Diabetes Control and Complications Trial. * 76% decrease in retinopathy risk for those without retinopathy at baseline; progression slowed by 54% in those with existing retinopathy. +DCCT Research Group. N Engl J Med 1993;329(14): Slide 82 **DCCT CV Outcomes: N Engl J Med 2005;353:

83 Risk of developing hypoglycaemia/complications (%) Reasons for poor glucose control Existing insulins force a trade-off between hypoglycaemia and complications Hypoglycaemia Complications HbA1C Slide 83 DCCT Research Group. N Engl J Med 1993;329:

84 Pumps Reduce Severe Hypoglycemia Published 2008 Pump vs. MDI Severe Hypoglycemia Rate Ratio Study Inclusion Criteria Meta-analysis of 22 studies Compared severe hypoglycemia Type 1 diabetes Duration > 6 months on pump Severe hypo frequency > 10 episodes /100 pt years on MDI Results MDI has 4.19 Xs more severe hypoglycemia than pumps Greatest hypo reduction found in those with highest initial rates of severe hypo Slide 84 Adapted from Pickup JC, Sutton AJ. Diabet Med 2008;25:

85 INSULIN PUMPS LOWER A1C MORE THAN MDI Studies Published Bruttomesso D et al. Continuous subcutaneous insulin infusion (CSII) in the Veneto region: efficacy, acceptability and quality of life. Diabet Med. 2002; 19 (8):

86 REDUCED CARDIOVASCULAR AND ALL CAUSE MORTALITY WITH CSII Presented at 50th EASD Annual Meeting, Vienna, Austria, Sept 2014 Prospective observational study of patients with T1D in the Swedish National Diabetes Registry Over 18,000 T1D patients followed for 7 years, : 2441 on pump therapy vs 15,727 on MDI Outcome Fatal CVD Events (%) Events/1000 person-years Hazard Ratio Injection P-value Pump Total mortality Injection Pump Gudbjörnsdottir S et al. Oral Presentation 196. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept , 2014; Vienna, Austria. 86

87 OpT2mise Study Insulin Pump Therapy in T2D Objective Design Methodology Compare efficacy and safety of pump therapy and MDI in patients with T2D who had not responded to a basal-bolus regimen after active insulin titration. Six month randomised controlled trial adults (A1C %) entered run-in study phase. MDI control group cross over to pump therapy at the end of the 6 month treatment period. Primary endpoint: HbA1c change from baseline to 6 months Secondary endpoints: Between group change in glycaemic variability parameters assessed by blinded CGM Number of severe hypoglycaemic events and DKA events Change in Insulin dosage between baseline and 6 months Change in lipid parameters, weight and blood pressure between baseline and 6 months N=331 N=495 87

88 PRIMARY ENDPOINT: PUMP THERAPY ACHIEVES GREATER A1C REDUCTION Mean A1C and 95% C.I. (%) Change in HbA1c - 6 months 10 CSII MDI A1C Reduction: 9 CSII group : -1.1% (A1c decreases 9.0% to 7.9%) MDI group: -0.4% (HbA1c drop from 9.0% to 8.6%) 8 Run-in (8 weeks) Study Phase (6 months + 3 weeks) 0.7% difference favouring pump therapy (p<0.001) Week Insulin pump therapy significantly improves glycaemic control compared to MDI in managing type 2 diabetes Reznik Y et al. Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial Lancet Oct 4;384(9950):

89 SIGNIFICANT AND DURABLE REDUCTION OF A1C AT 1 YEAR; OPTIMIZE STUDY (-0.7%) p< (-1.2%) p< Run-in Study Phase Continuation Phase (MDI crossover) Reznick et al and Optimize Study Group ADA Poster Presentation 2015

90 ΔA1C (MDI) - ΔA1C (CSII), % Cumulative Patientss Distribution (%) TREATMENT EFFECT ON A1C REDUCTION Difference in HbA1c according to baseline levels Distribution of HbA1c - 6 months 0 8 to 8.5% 8.6 to 9.2% 9.3 to 11.5% ±0 85% (P=0.105) % ±0 92% (P<0.02) % CSII MDI ±1 4% (P<0.001) month HbA1c (%) CSII group subjects with the highest baseline HbA1c (9.3 to 11.5%) achieved the largest improvement in glycemic control compared to MDI patients with the same baseline characteristics (-1.1±1.4%, p<0.001) Under CSII treatment, a larger proportion of the patient population achieved an HbA1c below 8% (55% versus 28%, p<0.001) Insulin pump therapy (CSII) is consistently superior to MDI therapy In the reduction of HbA1c and especially in patients with the highest baseline HbA1c

91 REDUCTION OF TOTAL DAILY INSULIN DOSE ON INSULIN PUMP THERAPY; OPTIMIZE STUDY -20% (p<0.001) -23% (p<0.0001) Run-in Study Phase Continuation Phase Reznick et al and Optimize Study Group ADA Poster Presentation 2015

92 Insulin Pumps further decrease absorption variability Pumps 3% Detemir *Percentages represent the coefficients of variation (CV) for insulin action as measured by the maximum glucose infusion rate in these euglycemic glucose clamp studies 27% Glargine Intrasubject Variability 46% NPH 59% Glucose lowering effect of intermediate and long-acting insulin can vary up to 46%, which explains drastic day-to-day variations in glucose levels despite using the same amount. Lepore et al. Diabetes 2000;49: Heise, Slide TC 92 et al, Poster Number 518

93 12-1a 2-3a 4-5a 6-7a 8-9a 10-11a 12-1p 2-3p 4-5p 6-7p 8-9p 10-11p Insulin (units/hour) AVERAGE HOURLY BASAL RATE BY AGE GROUP Published 2005 n= Age Age Age 3-10 Age > Hour of the Day Scheiner, Gary; Boyer, Bret A. Characteristics of basal insulin requirements by age and gender in Type-1 diabetes patients using insulin pump therapy. 93 Diabetes Research and Clinical Practice, 69 (2005) pg

94 CONTINUOUS GLUCOSE MONITORING - MULTIPLE BASAL RATES Patient, 39 y.o on MDI (Determir BD, Aspart TD) Patient complains waking up in the morning with high blood glucose levels despite going to bed with normal BG levels. 94

95 There are limitations of insulin injection therapy MDI CSII Disease progression - High doses of insulin are required to meet glycemic goals 1 - Frequency of injections increases vs Insulin dynamics - Insulin pooling - Greater intrasubject variability 3 - Dawn phenomenon Adherence - Perceived pain with injections 2 - Missed mealtime boluses - Social limitations, patient burden, and interference with daily activities 2 1. Wainstein J, et al. Diabetic Med. 2005: Peyrot M, et al. Diabetes Care. 2010;33: Lepore M, et al. Diabetes. 2000; 49:

96 There are challenges to insulin injection compliance US survey with 502 adults (T1 [23%],T2 [77%]) showed 1 : 77% have omitted insulin injection(s) 20% reported regular omission Barriers to compliance include 1,2 : - Perceived burden a lot of injections - Interference with daily activities - Injections are painful and embarrassing - Strict, complex treatment regimen Addressing interference with daily activities, injection pain, and embarrassment may contribute to improved treatment adherence 2 1. Peyrot M, et al. Diabetes Care. 2010;33: Rubin RR. Am J Med. 2005;118(Suppl3):27S 34S. 96

97 MDI Pump Patient Satisfaction: Pump vs. MDI Published 2005 Health-Related Quality of Life Assessment Lower is Better N= 197 Adults Type 1 or Type 2 Peyrot M, Rubin R. Diabetes Care. 2005;28:

98 ADVANCEMENTS IN PUMP THERAPY

99 Glucose mg/dl A NEW WAY TO TIGHTEN CONTROL The Paradigm REAL-Time insulin pump is integrated with continuous glucose monitoring. CGM reveals what fingersticks alone cannot Provides an update on your glucose levels every 5 minutes Fingersticks Alone Target Zone Continuous Glucose Monitoring 54 12AM 9AM 6PM 12MN Time of Day 99

100 BENEFITS INSULIN PUMP THERAPY: CONTINUOUS GLUCOSE MONITORING FUNCTION Continuous Glucose Monitoring function Predictive alerts

101 BENEFITS INSULIN PUMP THERAPY: CONTINUOUS GLUCOSE MONITORING FUNCTION Continuous Glucose Monitoring function Low glucose suspend function

102 Events per patient week AUC (mmol/lx min) LGS ASPIRE In-Home study Design In the ASPIRE In-Home study, the MiniMed sensor-augmented insulin pump with low suspend feature prevented more nocturnal hypoglycaemic events than an insulin pump without that feature. N=247, age 16 to 70 years Hypoglycemia Events per Patient-Week Mean AUC of Nocturnal Hypoglycaemia 6 30% reduction (p<0.001) % reduction (p<0.001) 5 32% reduction (p<0.001) Run-In Phase Study Phase Run-In Phase Study Phase 0 Threshold Suspend Control Threshold Suspend Control 0 Threshold Suspend Control Nocturnal Combined Day and Night Bergenstal RM,Klonoff DC, Bode BW, et al. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med. 2013;369(3):

103 AFTER YOU HAVE HAD YOUR CRASH The airbag saves your life

104 PREVENTING THE ACCIDENT

105 LATEST MEDTRONIC DIABETES TECHNOLOGY: MINIMED 640G WITH Improved Design: Designed with you in mind Full color with auto brightness display Ergonomic design; ntuitive navigation Waterproof Greater Convenience: Easy to use Programmable treatment reminders Preset meal bolus Advanced Protection: Continuous Glucose Monitoring Technology Suspend BEFORE hypoglycemia Basal insulin AUTOMATICALLY resumes when glucose levels are approaching normal range

106

107 Mean and SD of Glucose (mg/dl) Pump suspension time Avg. pump suspension time t (min) CLINICAL EVIDENCE OF SmartGuard TECHNOLOLGY: PILGRIM Study 1 80% of hypoglycaemic events were avoided by use of SmartGuard (defined as SG <70mg/dL) SmartGuard achieved 42% less time spent low compared to Low Glucose Suspend P< Hypoglycemia Sensor Predicted Sensor Excercise Pump Suspension Pump Resumption & Meal Suspend before low Suspend on low Time (min) from pump suspension SmartGuard TM performance Mean SG ± SD at Suspend 92 ± 7.2 mg/dl Mean SG ± SD at Lowest value 77 ± 23 mg/dl Mean SG ± SD for Suspend Duration 90 ± 35 min 1. Danne T, Tsioli C, Kordonouri O, et al. The PILGRIM Study: In Silico Modeling of a Predictive Low Glucose Management System and Feasibility in Youth with Type1 Diabetes During Exercise. Diabetes Technology & Therapeutics. 2014; 16(6):338:347.