Lack of Effectiveness of the GlucoWatch Biographer (GW2B) in Altering Glycemic Control in Children with Type 1 Diabetes H. Peter Chase 1, Roy Beck 2, William Tamborlane 3, Bruce Buckingham 4, Nelly Mauras 5, Eva Tsalikian 6, Tim Wysocki 5, Stuart Weinzimer 3, Katrina Ruedy 2, Dongyuan Xing 2, and the Diabetes Research in Children Network (DirecNet) Study Group. 1 Denver, CO; 2 Tampa, FL; 3 New Haven, CT; 4 Stanford, CA; 5 Jacksonville, FL; 6 Iowa City, IA.

Introduction: GlucoWatch G2 Biographer (GW2B) offers the potential to be a valuable adjunct to standard glucose monitoring (SGM) in type 1 diabetes (T1D). This multi-center trial was undertaken in youth with T1D to assess whether use of the GW2B with SGM lowers HbA1c and the frequency of hypoglycemia in comparison to use of SGM alone. Methods: 200 subjects aged 7 to 18 years were randomized to SGM or SGM plus GW2B use for 6 months. Other than use of the GW2B sensor, both groups were managed as similarly as possible. Subjects in both groups were provided with a PC to download sensor and meter results, to review glucose data as an aid in self-management, and to complete a questionnaire each week. Six-month data are available for 192 subjects. Results: HbA1c levels were similar at baseline and did not change significantly in either group during the study (Table). Use of the GW2B also did not significantly reduce the frequency of severe hypoglycemic events versus the SGM group. Both groups averaged ~5 glucose meter tests/day that was sustained throughout the study. In GW2B subjects, sensor use declined throughout the study from a mean value of 2.1/week in the first month to 1.4/week in the 6th month. Reasons given for declining use included: skin irritation (77%), skips too frequently (58%), alarms too frequently (47%), and does not provide accurate readings (34%). Group HbA1c (mean %) Hypoglycemia Mos Episodes (mean #/wk) Severe (% of pts) SGM % GW2B % P value Conclusions: Use of the GW2B in addition to SGM did not improve glycemic control or reduce the frequency of severe hypoglycemia. Skin reactions and other problems led to decreasing sensor use over time. ABSTRACT

INTRODUCTION The attainment of optimal glycemic control in youth with type 1 diabetes has been difficult for many reasons. The Diabetes Research in Children Network (DirecNet) study group is an NIH- (NICHD/NIDDK) funded collaborative study group evaluating the clinical usefulness of current and future glucose sensors in youth with diabetes. The use of a continuous glucose monitoring device in the home setting might help to improve glycemic control and to reduce severe hypoglycemic events.

PURPOSE To assess the merits of the GlucoWatch G2® Biographer (Cygnus Inc, Redwood City, CA) in the home environment during a six month randomized clinical trial in 200 children, ages 7-17 years, with type 1 diabetes

METHODS Initial outpatient evaluation of glycemic control: 48 to 72 hr CGMS (Medtronic MiniMed, Northridge, CA) profile 8-point SMBG for at least two days using OneTouch® UltraSmart® (Lifescan, Inc, Milpitas, CA)] HbA1c measured by HPLC in central laboratory The 99 subjects randomized to use the GW2B were given training and an unlimited supply of sensors and asked to use at least 4 per week during the first week; minimum of 2 per week thereafter (one during the day and one overnight).

METHODS (continued) All 200 subjects were given a computer for weekly downloads of their SMBG data and to complete a weekly questionnaire. GWB subjects also downloaded GWB data and answered questions on problems with the device. Phone contacts with all 200 families at 1, 2, 4, 16, and 20 weeks. Follow-up visits at 3 and 6 months with: Repeat of initial outpatient evaluation of glycemic control Psychosocial Questionnaires Grading of skin reactions (0 to 4 using modified Draize scale) for the GWB group.

PARTICIPANTS Eligibility Age 7 to 17 years T1D with use of insulin for at least one year HbA1c between 7.0% and 11.0% inclusive Stable insulin regimen (either a pump of at least 2 injections per day) for the two months prior with no plans to switch modality of insulin administration during the next six months Successful completion of home glucose monitoring using (1) an UltraSmart ® Meter and (2) a CGMS ™ Exclusion Criteria Prior use of a GW2B Current or past use of corticosteroids in the last 6 months Cystic fibrosis or another chronic illness

RESULTS SUBJECT CHARACTERISTICS

RESULTS (cont.) HbA1c

MEAN CGMS GLUCOSE RESULTS (cont.)

HYPOGLYCEMIA a – Defined as seizure or loss of consciousness. Percent with severe episode(s) anytime from baseline to 6 months. b – Fisher’s exact test. c – Excludes one subject in the Usual Care group who did not complete any of the weekly questionnaires. d –Wilcoxon rank-sum test. e- Restricted to subjects who completed ≥40 hours of CGMS use averaging ≥ 3 calibrations per 24 hours at baseline (N=96 Usual Care, N=97 GW2B), 3 months (N=85 Usual Care, N=85 GW2B) and 6 months (N=85 Usual Care, N=86 GW2B). Calculation of change from baseline to 6 months is restricted to subjects meeting these CGMS criteria at both time points (N=82 Usual Care, N=85 GW2B). f- CGMS episode of hypoglycemia defined as at least 2 values ≤60 mg/dL with no intermediate values >70 mg/dL. Distinct episodes were required to be separated by at least 30 minutes. RESULTS (cont.)

GWB USE First Month:2.1 ± 0.8 uses per week (64% = at least 2 sensors/ week) Third Month: 1.6 ± 0.7 uses per week (7 of the 99 subjects discontinued GW2B use) Sixth Month: 1.5 ± 0.6 uses per week (26 of the 98 subjects discontinued GW2B use) Questionnaire regarding non-use of the GW2B (55 subjects) 76% = “skin irritation” 56% = “skips to frequently” 47% = “alarms too frequently” 33% = “readings not accurate” 31% = “too busy to use it” 22% = “forget to use it” 18% = “did not help with diabetes management” ULTRA USE First Month: 5.1 ± 1.6 in Usual Care group, 5.6 ± 1.7 in GWB group Third Month: 5.1 ± 1.8 in Usual Care group, 5.3 ± 1.6 in GWB group Sixth Month: 4.8 ± 1.7 in Usual Care group, 5.1 ± 1.7 in GWB group

SKIN REACTIONS Skin Reactions observed by staff at any time in the 6 months: Of the 99 subjects: 1 = severe reaction 48 = moderate reactions RESULTS (cont.)

CONCLUSIONS The use of the GW2B in addition to standard glucose monitoring did not result in an improvement in glycemic control or a reduction in the frequency of severe hypoglycemia compared with the Usual Care group. Even in a group of children who were conscientious in performing standard glucose monitoring and in completing other study requirements, skin reactions and other problems led to decreasing sensor use over time.

Barbara Davis Center –H. Peter Chase –Rosanna Fiallo-Scharer –Jennifer Fisher –Barbara Tallant University of Iowa –Eva Tsalikian –Michael Tansey –Linda Larson –Julie Coffey Nemours Children’s Clinic –Tim Wysocki –Nelly Mauras –Larry Fox –Keisha Bird –Kelly Lofton Stanford University –Bruce Buckingham –Darrell Wilson –Jennifer Block –Paula Clinton Yale University –William Tamborlane –Stuart Weinzimer –Elizabeth Doyle –Kristen Sikes –Amy Steffen Jaeb Center for Health Research –Roy Beck –Katrina Ruedy –Craig Kollman –Dongyuan Xing –Cynthia Silvester