Diabetes Management with Continuous Glucose Monitoring & Multiple Daily Injections Aaron Michels MD
Outline SMBG & CGM by age group JDRF CGM Trial Sensor Augmented Insulin Pump Therapy for A1c Reduction (STAR 3 Trial) Focus on Pediatric Cohort CGM use in MDI vs. CSII Adult patients at the BDC CGM use in Type 2 Diabetes
Take Home Points: Advantages of Continuous Glucose Monitors Lower A1c Decreased Hypoglycemia Less Glucose Variability Weight Neutral or Weight Loss
Current Medical Practice Self Monitoring Blood Glucose (SMBG) Glucose (mg/dl) 400 360 320 280 240 200 160 120 80 80 Repeated Repeated finger sticks finger sticks are are required required to to obtain obtain glucose glucose readings readings Testing Testing is is generally generally performed performed before before meals meals Occasional Occasional measurements measurements provide provide only only limited limited information information about about glucose glucose levels levels no no direction direction or or rate rate of of change change 121 Pre Dinner 40 Pre Lunch 0 11:00 AM 1:00 PM 3:00 PM 5:00 PM 7:00 PM 9:00 PM 11:00 PM 1:00 AM Garg et al, Diabetes Care 1999.
Measurement of Blood Glucose Conventional Blood Glucose Meters 400 360 320 280 CGM Blood Glucose Calibration Point Glucose (mg/dl) 240 200 160 120 80 121 80 Pre Dinner 40 Pre Lunch 0 11:00 AM 1:00 PM 3:00 PM 5:00 PM 7:00 PM 9:00 PM 11:00 PM 1:00 AM
More Frequent Testing Improves HbA 1c in Type 1 Patients HbA 1c (%) 11 10 9 8 7 < 2 < 2 > 4 > 4 > 4 6 Initial No Contact Cross Over Intensify Schiffrin A, Belmonte M. Diabetes Care 1982;(5):479 84.
Self Reported SMBG Frequency from the T1D Exchange 0 2 3 4 5 6 7 9 10 SMBG readings per day Bergenstal R, et al. Presented at 5 th International Conference on Advanced Technologies & Treatment for Diabetes, Barcelona, 2012.
Total Group p < 0.001 HbA 1c by # of SMBG per Day (T1DM) Injection Pump p < 0.001 for each of the 4 age groups Garg, et al. Presented at 5 th International Conference on Advanced Technologies & Treatment for Diabetes, Barcelona, 2012.
Real Time Continuous Glucose Monitoring (CGM) Systems Abbott FreeStyle Navigator DexCom SEVEN Plus Medtronic MiniMed Paradigm REAL-Time
CGM use by Age Group T1D Exchange Type 1 Diabetes <6 6 12 13 17 18 25 26 49 50 Age range (years) Bergenstal R, et al. Presented at 5 th International Conference on Advanced Technologies & Treatment for Diabetes, Barcelona, 2012.
Mean A1c & Change from Baseline at 6 & 12 Weeks with CGM Patient Category Number of Patients Change from Baseline at Week 6 P-Value Change from Baseline at Week 12 P-Value Baseline A1c <7% Baseline A1c 7-9% Baseline A1c >9% 46-0.1 <0.021-0.05 <0.364 78-0.4 <0.001-0.5 <0.001 15-1.0 <0.017-1.4 <0.003 Reductions in A1c seen at all levels Bailey et al Diabetes Tech. & Ther 2007.
JDRF Study A1C Change in 7.0% Cohort with CGM Use 6 days/week in Month 12 0-0.2 Age > = 25 Age 15 24 Age 8 14 n = 34 n = 6 n = 15 Change in A1C (%) -0.4-0.6-0.8-0.5-0.5-0.5-0.7-0.8 0-26wks 0-52wks -1-1.0-1.2 JDRF CGM Study Group Diabetes Care 2009; 32:2047 2049
JDRF A1C < 7% Cohort: Change in the frequency of sensor glucose levels < 70 mg/dl Median minutes/day 120 100 80 p = 0.002 p = 0.16 p = 0.43 60 40 20 0 91 54 Baseline 26 wks RT CGM 96 91 Baseline 26 wks Control JDRF CGM Study Group Diabetes Care 2009;32:1378 1383
Sensor Augmented Insulin Pump Therapy for A1c Reduction (STAR) STAR 1 evaluated safety & efficacy of sensor augmented pump (SAP) therapy in T1D patients already using CSII Hirsh IB et al Diabetes Technol Ther 2008. STAR 2 determined optimal education & training protocols to transition MDI patients to SAP STAR 3 large prospective trial using continuous glucose monitoring SAP therapy compared to multiple daily injections in T1D patients
Effectiveness of Sensor Augmented Insulin Pump Therapy in Type 1 Diabetes STAR 3 Bergenstal R et al, NEJM 2010.
STAR 3 Study Design
Characteristics of the Patients Subject Baseline Characteristics Bergenstal R et al. N Engl J Med 2010;10.1056/NEJMoa1002853
Sensor Augmented Insulin Pump Therapy 9.0 Age 19 years HbA 1C (%) 9.0 8.5 8.0 * All patients MDI 7.5 SAP 7.0 0.0 0 3 6 9 12 * * Time (months) MDI = Multiple daily injections SAP = Sensor augmented pump therapy * HbA 1C (%) HbA 1C (%) 8.5 8.0 7.5 Age 7 18 years Time (months) MDI 7.0 SAP 0.0 0 3 6 9 12 9.0 8.5 8.0 7.5 * * MDI SAP 7.0 0.0 0 3 6 9 12 * * * * * * Bergenstal R et al, NEJM 2010.
Sensor Use & Change in A1c Using a Sensor-Augmented Insulin Pump with Continuous Glucose Monitoring, n=224 Bergenstal R et al. N Engl J Med 2010;10.1056/NEJMoa1002853 Bergenstal R et al, NEJM 2010.
Study Population Pediatric Cohort from STAR 3 Age group 7 12 13 18 Treatment SAP MDI SAP MDI n 43 39 35 39 A1C (%) 8.21 ± 0.56 8.19 ± 0.51 8.33 ± 0.53 8.40 ± 0.54 8.20 ± 0.54 8.37 ± 0.53 % male 65 54 51 51 Age (yr) 9.4 ± 1.7 10.1 ± 1.7 14.5 ± 1.4 15.2 ± 1.8 Diabetes duration (yr) 3.8 ± 2.4 4.2 ± 2.6 5.8 ± 3.5 6.7 ± 4.2 BMI (kg/m 2 ) 18.1 ± 2.4 18.5 ± 3.0 22.9 ± 3.6 22.6 ± 4.8 Taking more than three shots/d (%) 95 97 97 100 Slover RH et al, Pediatric Diabetes 2012.
Effectiveness of SAP therapy in children & adolescents with type 1 diabetes: STAR 3 7 12 years old SAP MDI 13 18 years old Slover RH et al, Pediatric Diabetes 2012.
Effectiveness of SAP therapy in children & adolescents with type 1 diabetes: STAR 3 7 12 years old A1c < 8% SAP MDI 13 18 years old A1c < 7.5% Slover RH et al, Pediatric Diabetes 2012.
CGM Use in CSII vs. MDI in Type 1 Diabetes Study Design Prospective, non-randomized, controlled study Sixty (60) adults with T1D enrolled 30 subjects on CSII 30 subjects on MDI A1c measured during screening, then monthly All patients were provided with adequate sensors throughout the study Study Duration: Six-months First 4 weeks: all subjects blinded from CGM values/trends/alarms Last 20 weeks: all subjects unblinded (real-time CGM provided) All CGMs were downloaded every visit Garg S et al, Diabetes Care 2011.
CGM Use in CSII vs. MDI in Type 1 Diabetes Study Populations Study Populations ITT PP-Compliant Therapy CSII* (n=30) MDI* (n=30) CSII* (n=17) MDI* (n=17) Age (yr) 36 ± 11 39 ± 8 38 ± 12 40 ± 7 T1D Duration (yr) 22 ± 11 22 ± 10 23 ± 11 26 ± 10 Screening A1c (%) 7.61 ± 0.76 7.62 ± 0.68 7.41 ± 0.49 7.56 ± 0.56 *Values are Mean ± SD, All baseline characteristics are similar, no significance difference between MDI and CSII groups. Garg S et al, Diabetes Care 2011.
A1c in CSII vs. MDI in ITT population (n=60) A1c (%) 8.2 8.0 7.8 7.6 7.4 7.2 7.6 7.6 8.0 7.8 7.7 7.6 7.4* 7.4 MDI Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 Time (week) 7.6 7.5 CSII 7.6 7.5 7.9 7.6 No significant difference in therapy groups; MDI vs. CSII, p=0.834; Repeated measure analysis Significant A1C change during the study; p<0.001 *Week 12 Unblinded vs. week 4 blinded; p<0.01 Garg S et al, Diabetes Care 2011.
CGM Use in CSII vs. MDI in Per Protocol Population 8.0 Per protocol CGM Compliant Study Population (> 6 days per week) A1c (%) 7.8 7.6 7.4 7.6 7.4 7.8 7.7 7.7 7.5 7.5 7.4* 7.4 7.6 7.4 7.2 MDI CSII 7.2 7.3 7.2 7.0 Screening Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 Time (week) In Clinic Visit No significant difference in therapy groups; MDI vs. CSII, p=0.3936; Repeated measure analysis *Significant A1C change during the study; p<0.001 Week 12 unblinded vs. week 4 blinded; p<0.01 Garg S et al, Diabetes Care 2011.
Change in Time Spent in Different Glucose Ranges: Blinded vs. Unblinded Periods 3 2 1.8 1.3 Time (hrs/day) 1 0 1 0.4 p=0.8 0.5 p=0.30 p=0.41 0.8 CSII MDI 2 1.4 3 <70mg/dl 70 180mg/dL >180mg/dL Glucose Range Garg S et al, Diabetes Care 2011.
Case Study: CSII Subject 31 year old M, T1D x 19 years Blinded: Month 1 18 May 15 Jun 2009 Unblinded: Months 2 6 15 Jun 02 Nov 2009 9.0 8.5 8.4 8.1 A1c (%) 8.0 7.5 7.5 7.6 7.3 7.2 7.0 6.5 1 2 3 4 5 6 Study Month
Case Study: CSII Subject 31 year old M, T1D x 19 yrs Blinded <70 70 180 >180 5% 40% 55% Unblinded <70 70 180 >180 5% 63% 33%
Case Study: MDI Subject 40 year old F, T1D x 38 years Blinded: Month 1 20-May 15-Jun-2009 Unblinded: Months 2-6 15-Jun 03-Nov-2009 8.0 7.7 7.5 A1c (%) 7.0 6.5 6.7 6.4 6.6 6.5 6.7 6.0 5.5 1 2 3 4 5 6 Study Month
Case Study: MDI Subject 40 year-old F, T1D x 38 yrs Blinded <70 70 180 180 >180 14% 39% 47% Unblinded <70 70 180 >180 16% 52% 33%
CGM in Type 2 Diabetes Subjects went through 4 cycles of 2 weeks on CGM and 1 week off (i.e. 3-month intervention); n=100 Subjects returned to usual care for the next 9 months The control group has usual care for 12 months. Ehrhardt N et al, J Diab Sci Tech 2011. Vigersky et al, Diabetes Care 2012.
Vigersky et al, Diabetes Care 2012.
Vigersky et al, Diabetes Care 2012.
CGM in Type 2 Diabetes - Summary Compared to Usual Care, CGM significantly improves glycemic control Analysis by usage highlights this difference: After 52 weeks, CGM significantly improved A1c in the higher usage group compared with Usual Care Improvement in the Usual Care group at 12 and 24 weeks only BP significantly improves in CGM group Weight and PAID scores improve more in the CGM group (p<0.05) CGM is beneficial to patients with type 2 diabetes Vigersky et al, Diabetes Care 2012.
T2D Case with CGM 64 y/o male with T2D for 14 years on 70/30 (80 U BID) A1c= 11.8% 4 weeks later: 48 units glargine & 8-10 units of glulisine QAC; no weight gain A1c= 7.8%
3 months later: 45 units glargine 7-9 units glulisine QAC 5 lb weight gain No Severe Hypoglycemia A1c = 6.6%
Advantages of CGM Lower A1c Decreased Hypoglycemia Less Glucose Variability Weight Neutral or Weight Loss ONLY IF REGULARLY USED!
Who Benefits From CGM? Patients with poor glucose control Patients with good glucose control Patients with type 1 diabetes Patients with type 2 diabetes on insulin Young and elderly Pregnancy, kids, hypoglycemic unawareness Patients on MDI and CSII
Thank You!