When Will CGM Replace SMBG? Roy W. Beck, MD, PhD. JAEB Center for Health Research Tampa, Florida

Transcription

1 When Will CGM Replace SMBG? Roy W. Beck, MD, PhD JAEB Center for Health Research Tampa, Florida

2 Financial Disclosures Dr. Beck does not have any personal conflicts of interest His employer, the JAEB Center for Health Research has received research or consulting funding or supplies for research studies from the following companies: Dexcom Abbott Diabetes Care Roche Animas Insulet Ascenia

3 Outline Evolution of CGM Evidence of CGM Benefit for T1D and T2D CGM Accuracy CGM Used Without BGM Confirmation Summary/Take Away Messages

4 First Real-time CGM GlucoWatch G2 Biographer FDA approved for adults in 2001 and children 7-17 yrs old in 2002

5 Real-time CGMs circa 2008 Dexcom: SEVEN Sensor (FDA approved for adults in 2006) Medtronic: Guardian REAL-Time Sensor (FDA approved for adults/children in 2005) Abbott: FreeStyle Navigator (FDA approved for adults in 2008)

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7 JDRF CGM Randomized Trial (2008) Baseline HbA1c >7.0%: HbA1c reduction seen in adults without increasing hypoglycemia but not in children or adolescents Regular CGM use much lower in adolescents than adults or younger children Similar benefit seen in all ages when CGM used regularly Baseline HbA1c <7.0%: benefit was seen both in HbA1c reduction and hypoglycemia reduction across ages Patient perception of CGM and satisfaction level varied Many felt that hassles outweighed benefits

8 CGM Clinical Trials in T1D The JDRF CGM RCT and other studies have shown benefit of CGM in adults with T1D using an insulin pump What about patients with T1D using MDI?

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10 T1D Exchange Registry: Lower HbA1c in CGM Users Regardless of Insulin Delivery Method Mean HbA1c % 9.5% 9.0% 8.5% 8.0% 7.5% 7.0% Injection only Injection + CGM 9.5% 8.8% 8.5% 7.8% 7.8% <13 N= % 8.7% 8.3% 13-<26 N=8269 Age (years) Pump only Pump + CGM 8.1% 7.8% 7.4% 7.4% 26 N=5185

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12 DIAMOND: RCT of 158 Adult MDI Users with T1D Randomization to CGM (Dexcom G4 Platinum CGM System with software 505) or Usual Care for 6 mos Mean baseline HbA1c 8.6% in both groups Mean CGM usage 6.7 d/wk at 6 mos Compared with control group, CGM Reduced HbA1c by 0.6% Increased time-in-range Reduced biochemical hypoglycemia Reduced glycemic variability Was associated with very high CGM Satisfaction Scale scores (substantially higher than in JDRF CGM RCT)

13 DIAMOND CGM Usage Week 4 Visit (N=105) Week 12 Visit (N=103) Week 24 Visit (N=102) Mean CGM usage, days/week days/week 0% 1% 2% 6 days/week 94% 96% 89% Mean % of CGM readings captured 95% 93% 90% CGM usage similarly high in participants with HbA1c >9.0% and in those >60 years old

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15 GOLD Randomized Trial Randomized Trial of 161adult MDI users with T1D Crossover over trial with 2 periods: CGM (Dexcom G4 Platinum) or Usual Care Mean baseline HbA1c 8.6% CGM usage overall 88% CGM: Reduced HbA1c by 0.4% compared with control (P<0.001) Increased time-in-range Reduced biochemical hypoglycemia Reduced glycemic variability Had high treatment satisfaction and improved quality of life

16 CGM for Type 2 Diabetes

17 DIAMOND T2D Study Randomized Trial of 158 adult MDI users with T2D Randomly assigned to CGM (Dexcom G4 Platinum CGM System with software 505) or Usual Care Mean baseline HbA1c 8.5% in both groups Primary outcome HbA1c at 24 weeks: completed by 96% Results CGM usage in month 6: >6 days/wk in 93% Mean HbA1c decreased 1.0% in CGM Group and 0.6% in Control Group (P=0.005) CGM increased time-in-range and reduced hyperglycemia Little hypoglycemia in both groups CGM Satisfaction Scale scores extremely high (substantially higher than in JDRF CGM RCT)

18 CGM Usage 6 Days/Week % of Participants Week 4 Week 12 Week 24 6 days/wk 0 days/wk CGM use similarly high with baseline HbA1c >9.0% and with age >60 years 18

19 Abbott FreeStyle Libre not yet available in US 14-day sensor Factory calibrated swipe

20 Abbott Libre Study: REPLACE

21 REPLACE Randomized Trial Randomized Trial of 224 insulin users (95% MDI) with T2D Randomization 2:1 to Libre or Usual Care Mean baseline HbA1c 8.7% Primary outcome: HbA1c at 6 mos

22 REPLACE Randomized Trial Results Libre usage overall 93% SMBG tests 0.3 versus 3.8 times/day Mean sensor scans per day 8 HbA1c decreased 0.3% in both groups (P=0.82) Libre reduced time < 70 mg/dl by 28 min/day (P<0.001) No severe hypo events High treatment satisfaction and quality of life with Libre

23 CGM for Patients with Type 2 Diabetes Using Basal Insulin No randomized trials to date focusing on these patients Dexcom sponsoring upcoming RCT to assess CGM in patients with T2D using basal insulin (MOBILE)

24 Is CGM Accurate Enough to Replace BGM?

25 CGM Accuracy Over Time Abbott Libre (12.3%) Medtronic Enlite 3 (10.5%) Faccinetti A. Sensors 2016

26 Dexcom Sensor Accuracy Through the Generations MARD

27 Accuracy of Current CGM Sensors Mean Absolute Relative Difference (MARD) Percentage within 20 mg/dl or 20% Dexcom G5 9.0% 93% Medtronic Enlite % 88% Abbott Libre 12.3% 84%

28 Accuracy of Current CGMs by Sensor Day Mean Absolute Relative Difference Day 1 ~Day 3-4 ~Day 7 Dexcom G5 10.7% 8.0% 8.5% Medtronic Enlite % 8.9% 9.5% Abbott Libre 13.8% 13.3% 12.3%

29 Accuracy of Current CGMs in Glucose Ranges Reference Glucose Range <70 mg/ dl MAD mg/dl mg/ dl MARD >180 mg/dl MARD Dexcom G % 8.0% Medtronic Enlite 3 Abbott Libre estimated % 10.0% % 10.0%

30 Accuracy of Current CGMs in At-Home Studies Using BGM as Reference Dexcom G5/G4 (505 software) REPLACE-BG: N=37,834 MARD 13% Bailey et al: N=13,195 MARD=11% Abbott Freestyle Libre Olafsdottir et al: N=3,602 MARD=13%

31 Comparison of Dexcom G5 and Abbott Libre Freckman et al (ADA 2017 poster) 20 participants wore 2 of each sensor for 14 days Accuracy compared with blood glucose meter MARD: Dexcom 9.6% Libre 11.0%

32 Coming Soon: Dexcom G6 Sensor 10 Day dura;on sensor Acetaminophen Blocking 1 Calibra;on Per Day (aaer start) 30% Thinner Wearable Simple, Push Bu.on Sensor Applicator

33 Dexcom G6 Sensor Accuracy Study Results Overall N Mean ARD %20/20 G6 All Data % 96.1% G6 Adults % 99.4% G5 Adults % 93% 49 subjects (32 Adult, 17 Pediatric) with T1D Accuracy assessed over 10 days with YSI Day 1 N Mean ARD %20/ % 90.1% % 100% % 84% Calibrated once per day ager start

34 G6 Accuracy with No Calibration Study Results Overall Day 1 N Mean ARD %20/20 N Mean ARD %20/20 G6 No Cal % 95.5% % 94.5% G6 1/day % 96.1% % 90.1%

35 How Does CGM Accuracy Compare with BGM Accuracy

36 Blood Glucose Meter Accuracy Ekhlaspour et al, JDST meters: MARD=5.6%-20.8% 9 with MARD >10%

37 Diabetes Technology Society Study Assessed accuracy of 18 BG meters, each tested in 3 substudies, among 1,035 study participants Passing Standard: BG within 15% of reference for BG >100 mg/dl and within 15 mg/dl for BG <100 mg/dl Passing score: >90% meeting standard Results: 6 of 18 meters had passing grade in all 3 substudies 5 of 18 had passing grade in 2 out of 3 3 of 18 had passing grad in 1 out of 3 4 of 18 failed in all 3 substudies

38 Diabetes Technology Society Study Meters with passing grade in all 3 substudies Bayer Contour Next Roche Accu-check Aviva Plus Walmart ReliOn Agamatrix CVS Advanced Abbott FreeStyle Lite Roche Accu-Check Smart View

39 CGM Versus BGM Accuracy A few blood glucose meters are more accurate than CGM but CGM accuracy (particularly Dexcom) is as good as or better than many meters Important to select accurate meter for CGM calibration as long as calibration is needed

40 How Accurate Does CGM Need to Be for Nonadjunctive Use Kovatchev et al Analyzed study data and conducted in-silico simulations Simulated 7 CGM accuracy levels with MARD from 3%-22% Concluded that using CGM alone for dosing decisions feasible if MARD <10%. Below 10% not much gain unless it relates to a reduction in outliers

41 What Have Clinical Studies Shown about Safety of Dosing Insulin Based on CGM Alone?

42 Abbott Libre Study: REPLACE

43 Abbott Libre Study: IMPACT

44 IMPACT Randomized Trial Randomized Trial of 120 adult MDI users with T1D Randomization to Libre or usual care with SMBG Mean baseline HbA1c 6.7% Primary outcome: Change in hypoglycemia (time <70 mg/dl)

45 IMPACT Randomized Trial Results Libre usage overall 93% Libre reduced time < 70 mg/dl by 74 min/day (P<0.001) Libre increased TIR, reduced hyperglycemia and variability No difference in HbA1c Severe hypo events: 2 in Libre and 4 in Control Group SMBG testing 0.5 times/day versus 5.6 times/day Mean sensor scans per day 15 High treatment satisfaction and quality of life with Libre

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47 Synopsis of Study Design Cohort: Pump users >18 years old with HbA1c <9% Run-in phase for CGM training 226 participants randomly assigned 2:1 to either CGMonly or CGM+BGM group Both groups used Dexcom G4 Platinum CGM System with an enhanced algorithm (software 505) Primary outcome Time in range ( mg/dl) over 26 weeks of trial

48 Protocol Adherence 26-week trial completed by 96% of participants CGM usage over 26 wks CGM-only: mean=6.7d/wk with 91% using >6d/wk CGM+BGM: mean=6.8d/wk with 95% using >6d/wk No participants completing the trial discontinued CGM BGM usage over 26 wks CGM-only: mean 0.8 tests/day (not including 2 for CGM calibration) CGM+BGM: mean 5.4 tests/day

49 Results Virtually identical results in the CGM-only and the CGM +BGM groups for: Time in range mg/dl Mean glucose Hyperglycemia Hypoglycemia Glycemic variability HbA1c Severe hypoglycemia: 0 in CGM-only group; 1 in CGM +BGM group No DKA in either group

50 Summary Multiple studies have shown better glycemic outcomes with CGM compared with SMBG in adults for both pump and MDI users for T1D and T2D Studies with current generation Dexcom G4/G5 and Abbott Libre have demonstrated remarkably high degree of perseverance in sensor use and high degree of patient satisfaction across entire HbA1c and adult age ranges Much higher use and satisfaction than with earlier CGMs tested in JDRF CGM RCT

51 Summary Accuracy studies have suggested that current sensors are sufficiently accurate to be used safely for insulin dosing Accuracy as good as or better than many blood glucose meters REPLACE-BG RCT (Dexcom) and REPLACE/IMPACT RCTs (Abbott Libre) have demonstrated that CGM can be used safely for insulin dosing without BGM confirmation Additional CGM studies needed in young children and adolescents-young adults

52 Regulatory Status In Europe, Dexcom G5 and Abbott Libre both have CE Mark to be used without BGM confirmation In U.S., Dexcom G5 is the only CGM that is approved by the FDA for nonadjunctive use (approved early 2017) Subsequent to the FDA approval in early 2017, the Centers for Medicare and Medicaid (CMS) classified the Dexcom G5 as a durable medical good, allowing it to become a covered benefit for patients with T1D or T2D using MDI or CSII

53 Take Away Messages Does CGM Improve Outcomes Compared with BGM? Yes, for patients with T1D or with T2D using basalbolus insulin therapy with pump or injections Patient perseverance with use and satisfaction with CGM substantially higher than with older generation sensors tested in the JDRF CGM RCT

54 Take Away Messages Is CGM Accurate Enough to Replace BGM? Yes! Each generation of sensor has become more accurate Current sensors, particularly Dexcom G5/G6, are more accurate than many blood glucose meters First day of sensor not as accurate as subsequent days Accuracy of BGM important for sensors requiring calibration

55 Take Away Messages Can CGM Fully Replace BGM? Not completely Except for Libre, BGM needed for calibration Even if sensor is factory calibrated, having the ability to recalibrate will be of value BGM needed when CGM glucose reading doesn t seem right But, BGM use can be substantially reduced when CGM is used

56 Take Away Messages For Which Patients Could CGM Be Near-Total Replacement for BGM? All patients with TID Patients with T2D using CSII or MDI Patients with T2D using basal insulin? For Which Patients Is CGM Unlikely to Be Widely Adopted Patients with T2D not using basal-bolus insulin In future: simple to use, unobtrusive, low cost sensors could change this

57 Elimina;ng Fingers;cks Is Possible with CGM