Virtual Diabetes Specialty Clinic: A Study Evaluating Remote Initiation of Continuous Glucose Monitoring
Phase: NA
Conditions: Type 1 Diabetes, Type 2 Diabetes
Sponsor: Jaeb Center for Health Research

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Virtual Diabetes Specialty Clinic: 
A Study Evaluating Remote Initiation of Continuous 
Glucose Monitoring 
 
Version Number: v. 4.1 
6 July 2021 
 

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KEY ROLES 
 
Protocol Chair/Director 
 
Name, degree 
Grazia Aleppo, M.D. 
Title 
Protocol Chair 
Institution Name 
Northwestern University Feinberg School of Medicine 
 
JCHR Coordinating Center Director 
 
Name, degree 
Robin L. Gal, M.S.P.H. 
Title 
Project Director 
Institution Name 
Jaeb Center for Health Research 
 
Medical Monitor 
 
Name, degree 
Roy Beck, M.D., Ph.D. 
Title 
Executive Director 
Institution Name 
Jaeb Center for Health Research 
 

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TABLE OF CONTENTS 
CHAPTER 1: BACKGROUND INFORMATION ............................................................................................. 10 
1.1 Introduction ....................................................................................................................................... 10 
1.2 Rationale ............................................................................................................................................ 11 
1.3 Potential Risks and Benefits .............................................................................................................. 12 
1.3.1 Known Potential Risks ................................................................................................................ 12 
1.3.2 Known Potential Benefits ............................................................................................................ 12 
1.3.3 Risk Assessment .......................................................................................................................... 12 
1.4 General Considerations...................................................................................................................... 12 
 STUDY ENROLLMENT AND BASELINE DATA COLLECTION ............................................... 13 
2.1 Participant Recruitment and Informed Consent ................................................................................ 13 
2.1.1 Informed Consent and Authorization Procedures ....................................................................... 13 
2.2 Participant Inclusion Criteria ............................................................................................................. 13 
2.3 Participant Exclusion Criteria ............................................................................................................ 14 
2.4 Screening Procedures ........................................................................................................................ 14 
2.5 Collection of Baseline Data and Testing ........................................................................................... 14 
2.5.1 HbA1c ......................................................................................................................................... 15 
2.6 CGM System ..................................................................................................................................... 15 
2.7 Blinded CGM .................................................................................................................................... 15 
2.8 Psychosocial Screening Questionnaires ............................................................................................ 16 
 STUDY PROCEDURES AND DATA COLLECTION .................................................................. 17 
3.1 Overview ........................................................................................................................................... 17 
3.2 Virtual Clinic Team Interactions with Study Participant .................................................................. 17 
3.2.1 Virtual Clinic Team Interactions with Personal Healthcare Provider ......................................... 17 
3.3 CGM Initiation (Unblinded Use) ....................................................................................................... 17 
3.4 CGM Use and Data Interpretation ..................................................................................................... 18 
3.5 Insulin Dose Changes ........................................................................................................................ 18 
3.5.1 Decision Support ......................................................................................................................... 18 
3.5.2 Personal Healthcare Provider Notification .................................................................................. 18 
3.6 Follow-up Data Collection ................................................................................................................ 18 
3.6.1 HbA1c ......................................................................................................................................... 18 
3.7 Data Uploads ..................................................................................................................................... 19 
3.8 Insulin Delivery and Collection of Insulin Data ................................................................................ 19 
 QUESTIONNAIRES ................................................................................................................. 20 

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 MISCELLANEOUS CONSIDERATIONS ................................................................................... 21 
5.1 Adverse Events .................................................................................................................................. 21 
5.2 Device Issues ..................................................................................................................................... 21 
5.3 Study Costs ........................................................................................................................................ 21 
5.4 Participant Compensation .................................................................................................................. 21 
5.5 Participant Withdrawal ...................................................................................................................... 21 
5.5.1 Pregnancy .................................................................................................................................... 22 
5.6 Contact Information ........................................................................................................................... 22 
5.6.1 Personal Healthcare Provider Information .................................................................................. 22 
5.7 Confidentiality ................................................................................................................................... 22 
5.8 Quality Assurance and Monitoring .................................................................................................... 22 
 STATISTICAL CONSIDERATIONS .......................................................................................... 24 
6.1 Statistical and Analysis Plan .............................................................................................................. 24 
6.2 Sample Size ....................................................................................................................................... 24 
6.3 Outcome Measures ............................................................................................................................ 24 
6.4 Description of Statistical Methods..................................................................................................... 24 
6.4.1 Analysis Cohorts ......................................................................................................................... 24 
6.5 Analysis of Efficacy Outcomes ......................................................................................................... 24 
6.6 Subgroup Analyses ............................................................................................................................ 25 
6.7 Safety Analyses ................................................................................................................................. 25 
6.8 Baseline Descriptive Statistics ........................................................................................................... 25 
6.9 Multiple Comparisons/Multiplicity ................................................................................................... 25 
6.10 Additional Analyses ........................................................................................................................ 25 
 ETHICS/PROTECTION OF HUMAN PARTICIPANTS .............................................................. 26 
7.1 Ethical Standard ................................................................................................................................. 26 
7.2 Institutional Review Boards .............................................................................................................. 26 
7.3 Informed Consent Process ................................................................................................................. 26 
7.3.1 Consent Procedures and Documentation ..................................................................................... 26 
 REFERENCES ......................................................................................................................... 27 
 

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LIST OF ABBREVIATIONS 
ABBREVIATION 
DEFINITION 
BGM 
Blood Glucose Meter 
CDC  
Centers for Disease Control and Prevention 
CDCES 
Certified Diabetes Care and Education Specialist 
CFR 
Code of Federal Regulations 
CGM 
Continuous Glucose Monitor 
DKA 
Diabetic Ketoacidosis  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice  
HbA1c 
Hemoglobin A1c 
IRB 
Institutional Review Board 
MDI 
Multiple Daily Injections 
SH 
Severe Hypoglycemia 
T1D 
Type 1 Diabetes 
T2D 
Type 2 Diabetes 

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PROTOCOL SUMMARY 
PARTICIPANT AREA 
DESCRIPTION 
Title 
Virtual Diabetes Specialty Clinic: A Study Evaluating Remote Initiation 
of Continuous Glucose Monitoring
Précis 
This study will assess feasibility and efficacy of establishing a virtual 
diabetes clinic with a focus on introduction of CGM technology and 
ongoing CGM use to minimize such rate-limiting factors as geography, 
cost and access to specialty care
Objectives 
The objective of this study is to evaluate a virtual diabetes clinic model, 
for adults with either T1D or T2D, that supports integration of CGM into 
diabetes self-management and evaluates use of decision support 
technology within the virtual clinic model.
Study Design 
Single-arm prospective longitudinal study
Eligibility Criteria 
Inclusion Criteria 
 
Age >18 years old 
 
Diagnosis of type 1 diabetes or type 2 diabetes and using insulin 
therapy (at least 3 injections of insulin per day or insulin pump that 
is compatible with Tidepool software) Multiple daily injection (MDI) 
users must be willing to use a device provided by the study that 
records the injection dosages and/or enter insulin dosing 
information through an app 
 
See a healthcare provider at least once a year 
 
Resident of United States and plan to reside in the U.S. for the 
duration of the study *This requirement is due to virtual clinic 
license requirements and U.S. use restrictions for some study 
software and devices. Not all U.S. states may be eligible for 
inclusion due to virtual clinic license status. 
 
Use either an Android or iOS smartphone that is compatible with app 
requirements that are needed for the study 
 
Access to a compatible computer with internet 
 
Understand written and spoken English 
 
Willing and able to follow the study procedures as instructed 
Exclusion Criteria 
 
Current use of a closed loop system where an insulin pump and 
CGM share information and insulin dose is automatically adjusted 
based on glucose reading 
 
Current CGM use where Time in Range is ≥60% or Time <54%  
≤1.0%). 
 
Current use of any off-label glucose-lowering medications for 
diabetes type (Example: T1D use of non-insulin, anti-diabetic 
medications including SGLT2 inhibitors) *Use of such medications 
during the study will also be prohibited. 
 
Females who are pregnant, intending to become pregnant, or 
breastfeeding during the study 
 
Current renal dialysis or plan to begin renal dialysis during the study 
 
Active cancer treatment 
 
Extreme visual or hearing impairment that would impair ability to 
use real-time CGM 
 
Known adhesive allergy/prior skin reaction or skin reaction 
identified during the blinded CGM use phase that would preclude 
continued CGM use 
 
Participation in a different diabetes management study during the 
study 

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PARTICIPANT AREA 
DESCRIPTION 
 
Planned relocation to a state other than current state of residence 
during the study if virtual clinic is not licensed in the new state. 
Individuals working routinely in a state other than current state of 
residence in the next six months are also ineligible if the virtual 
clinic is not licensed in that state. 
Sample Size 
The recruitment target is 300 initiating CGM. 
Outcomes 
Efficacy Outcomes: CGM use; CGM metrics for hypoglycemia (<54 and 
<70 mg/dL), hyperglycemia (>180 and >250 mg/dL), time in range (70-
180 mg/dL), mean glucose, and glycemic variability (coefficient of 
variation); HbA1c; participant- reported outcomes including psychosocial 
and diabetes treatment satisfaction questionnaires 
Safety Outcomes: Severe hypoglycemia, diabetic ketoacidosis, 
hospitalizations, and emergency room visits
Participant Duration 
Study participation will be up to 12 months.
Protocol Overview/Synopsis 
Patient Population 
Adults ≥ 18 years with type 1 diabetes or type 2 diabetes using insulin 
therapy will be enrolled. Although the primary focus of the study is to 
enroll non-CGM users, CGM users whose glycemic control is suboptimal 
can be enrolled. Potential participants may be recruited through insurance 
providers, primary care networks, or health care providers. 
 
Baseline Data Collection 
Baseline data collected will include demographics, height and weight, 
socioeconomic status, diabetes history, knowledge of and experience with 
diabetes devices, medical history and medications, and health-related 
physical activity. Questionnaires will collect information related to 
hypoglycemia awareness, treatment satisfaction, and psychosocial issues. 
Participant contact information will be collected. Contact information for 
the participant’s diabetes healthcare provider will also be collected. 
 
HbA1c 
Participant will receive fingerstick HbA1c kits that will be sent to a 
central lab for measurement after enrollment and at 13 weeks, 26 weeks, 
39 weeks, and 52 weeks. 
 
Contact between Study Team and Participant 
Each participant will be assigned to work with virtual clinic team 
members. Mental health service support options for diabetes-related 
mental health issues will be discussed as needed. 
 
Virtual clinic team members will check in with participants during the 
initial six months of study follow up to review CGM data and 
recommendations related to diabetes management. Participants who 
continue in the optional extended follow-up phase after the first six 
months can contact the virtual clinic as needed.  
 
CGM Use 
Participants who do not currently use a CGM will use a blinded CGM 
device for a single sensor wear period prior to CGM initiation. 
Participants may be asked to use a blinded CGM for an additional sensor 
wear period(s) if enough CGM data are not available to establish a 
baseline that can be used as baseline comparator data. Current CGM users 
will be asked to share their CGM data to confirm that they meet study 
eligibility criteria and to establish a baseline that can be used as baseline 
comparator data. Virtual training will include CGM set up, sensor 
insertion, alerts and alarms, uploading data, and visualizing data. 
 
Changes in Insulin Dosing

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PARTICIPANT AREA 
DESCRIPTION 
If the virtual clinic team believes that changes in insulin type or dosing 
should be considered, they will work with the participant to implement 
any such changes. Decision support tools, which include use of a mobile 
application, may be used if available to provide the virtual clinic team 
with potential recommendations regarding insulin use.
 

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SCHEDULE OF STUDY VISITS AND PROCEDURES 
1 
This is a remote study design with virtual visits; eligibility and other study questionnaires are by participant self-report.  
2 
3 
 
 
 
 
Virtual Clinic Training Phase 
(0-13 Weeks) 
Virtual Clinic 
Follow Up 
Phase 
Optional 
Extended 
Participant 
Follow Up 
 
Enrollment 
Initial Virtual 
Clinic Contact 
Baseline CGM 
Data Collection 
Training 1 
(Week 0) 
Training 2 
(Week 1) 
Training 3 
(Week 3) 
CGM Follow 
Up 
(Weeks 4, 8) 
CGM Follow Up 
(Week 13) 
Follow up 
(>13-26 
Weeks) 
Follow Up 
(>26-52 Weeks) 
TARGET WINDOW 
 
Within 7 Days 
from 
Completion of 
Enrollment 
Questionnaires 
 
Day 0 
Day 7-14 
Day 21-28 
 
Weeks 12-14 
 
 
ICF 
 Eligibility Confirmation 
X 
 
 
 
 
 
 
 
X* 
X* 
Baseline Data Collection 
 Contact Information 
 Demographics 
 Medical History 
 Questionnaires 
X 
 
X 
 
 
 
 
 
 
 
Follow-Up Data Collection** 
 
 
 
 
X 
X 
X 
X 
X 
X 
HbA1c*** 
 
 
X 
 
 
 
 
X 
X 
X 
Video Tutorials / Access to 
Resource Materials 
 
Examples: 
CGM Overview 
Parts of CGM 
Examples: 
HbA1c Sample 
Collection 
CGM Setup 
Examples: 
Understanding 
Your Real-Time 
Data 
How to Change 
Sensor 
Examples: 
How to Upload 
CGM Data 
How to View 
Reports 
Understanding 
Your Ambulatory 
Glucose Profile / 
Data Patterns 
X 
X 
X 
X 
X 
Contact with Study Team† 
 
X 
X 
CGM Initiation 
CGM Data 
Interpretation 
CGM Data 
Review 
Goal Setting 
X 
X 
X 
X 
CGM Use†† 
 
 
~2 Week Blinded 
CGM Use††† 
Start of 26-Week 
Unblinded CGM 
Use 
X 
X 
X 
X 
X 
X 
*. Participants will be asked to extend follow up for an additional 26 weeks and sign an addendum ICF if they plan to continue to use CGM after the first 26 weeks. Virtual Clinic follow up will be available to participants on an as-needed 
basis after the first 26 weeks. 
**Participants will be asked to complete questionnaires monthly after CGM Initiation. A final questionnaire will be elicited at the earlier of CGM discontinuation or completion of study follow up (~52 weeks). 
***HbA1c checks prior to unblinded CGM initiation, and at 3-month intervals following CGM initiation (~13 weeks, 26 weeks, 39 weeks, and 52 weeks)  
†Follow up may be via phone, text, virtual (i.e. Skype), or app. outside of scheduled training. Additional follow up may be conducted as needed. Participants may follow up with study team as needed. 
††CGM supplied for blinded data collection will be provided. CGM supplies for six months of unblinded use will be provided for those who successfully complete blinded data collection. 
†††Current CGM users are not required to wear blinded CGM unless current CGM data cannot be shared to establish baseline. 

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Chapter 1: Background Information 
4 
1.1 Introduction 
5 
The advent of home blood glucose meter (BGM) testing from a fingerstick in the 1980s had a 
6 
major impact on the management of diabetes, particularly in individuals using insulin. While 
7 
BGMs remain the method of glucose monitoring for most people with diabetes, continuous 
8 
glucose monitoring (CGM) systems are now available and have replaced BGM testing for 
9 
primary glucose monitoring in an increasing number of adults and children with type 1 diabetes 
10 
(T1D) and some with type 2 diabetes (T2D). 
11 
The CGM device has a sensor that is inserted in the subcutaneous space and measures the 
12 
interstitial fluid glucose concentration. Some CGMs, such as the Dexcom G6, provide real-time 
13 
glucose measurements every five minutes with alerts for rising or dropping glucose levels and 
14 
threshold alarms when a preset hyperglycemia or hypoglycemia level is reached. Other CGMs 
15 
such as the Abbott FreeStyle Libre, which also has been referred to as flash glucose monitoring, 
16 
show glucose levels only when the user passes the receiver over the sensor to transmit the 
17 
glucose data to the receiver; glucose recordings are every 15 minutes. 
18 
The accuracy of current generation CGMs approaches that of blood glucose meters. For the 
19 
current generation of the Dexcom and Abbott sensor, the mean absolute relative difference, a 
20 
common metric for assessing accuracy when sensor glucose values are compared with reference 
21 
glucose values, is about 10% or lower, which is in about the middle of the range of accuracy of 
22 
current blood glucose meters1,2. This accuracy is what led the FDA to approve the device for 
23 
non-adjunctive use in dosing insulin. 
24 
The efficacy of CGM has been demonstrated in randomized trials of adults and youth with type 1 
25 
diabetes (T1D)3-10, adults with type 2 diabetes (T2D) using insulin11-13, and in a registry of adults 
26 
and youth with T1D 14; including reductions in HbA1c levels, duration of hyperglycemia and 
27 
hypoglycemia, and increased time spent with glucose levels between 70 and 180 mg/dL, which is 
28 
the target range. Studies not only demonstrated improvement in HbA1c and reduction in 
29 
hypoglycemia but also showed that after six months, approximately 90% of individuals were 
30 
using CGM on a daily or near-daily basis. CGM users have reported substantial satisfaction with 
31 
use of the device and improved quality of life.3,9,15-18 
32 
Studies have demonstrated the benefits of CGM in individuals with T1D or T2D treated with 
33 
multiple daily injections of insulin3,5,6,9,15,16. In the T1D Exchange registry, CGM use 
34 
(predominately Dexcom) was associated with lower HbA1c levels irrespective of whether a 
35 
pump or injections are used for insulin delivery. Mean HbA1c was 9.1% in individuals not using 
36 
a pump or CGM, 8.6% in those using a pump but not a CGM, 7.9% in those using both a pump 
37 
and CGM, and 8.0% in those using injections and CGM. 
38 
Current generation CGMs have been shown to have a good safety profile. The ease of insertion, 
39 
lack of need for calibration or routine blood glucose meter testing, and extension of sensor life 
40 
have all made the initiation of CGM easier. Thus, the time has come to consider initiation of 
41 
CGM use as similar to BGM use. 
42 
CGM use has been endorsed for individuals with T1D by the American Diabetes Association, 
43 
the American Association of Clinical Endocrinologists, the Endocrine Society, and the 
44 
International Society for Pediatric and Adolescent Diabetes. Despite these recommendations and 
45 

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the compelling evidence of the benefits of CGM, many individuals with T1D or insulin-using 
46 
T2D have not incorporated CGM into their diabetes management. Although there are not specific 
47 
data to cite, it is likely that the low rate of CGM adoption partially reflects a lack of awareness 
48 
about CGM among primary care providers, who are responsible for the care of not only most 
49 
adults with type 2 diabetes but also those with type 1 diabetes 19-21. Lack of provider resources to 
50 
introduce and incorporate CGM into patient diabetes self-management may also be a limiting 
51 
factor to technology adoption, as usage is low even among some leading diabetes centers14,22. 
52 
Although demand for endocrinology care continues to grow, access to specialized care may be 
53 
impacted by geographic isolation and a shortage in the number of endocrinologists in the United 
54 
States. 
55 
A recently completed feasibility study assessed whether adults with T1D or T2D using insulin 
56 
could be trained virtually, outside of the clinic, to initiate and use CGM as part of their diabetes 
57 
self-management. This study demonstrated that a virtual approach outside of the clinic can be 
58 
used for successful CGM initiation and incorporation into diabetes self-management for adults 
59 
with T1D or T2D using insulin. There was a substantial reduction in HbA1c in most participants, 
60 
as well as a reduction in estimated mean glucose, with an increase in the amount of time in range 
61 
spent with glucose levels between 70 and 180 mg/dL, which is the generally accepted target 
62 
range for most adults with T1D or T2D (excluding pregnancy)23. Further, participant-reported 
63 
outcomes evaluated before and after exposure to the virtual clinic revealed improvements in 
64 
glucose monitoring satisfaction, confidence in treating hypoglycemia, and reductions in diabetes 
65 
distress. 
66 
It is important for those using CGM to understand how to use the data from the CGM. This 
67 
includes looking at patterns and trends to understand what their glucose is doing and how it 
68 
changes while sleeping, in between meals, and during periods of exercise and stress. 
69 
Understanding CGM data extends beyond responding to alerts and warnings when levels are too 
70 
high and too low. Current CGM users may benefit from virtual clinic support to better 
71 
understand their CGM data, as not all CGM users meet goals for time in range or HbA1c target. 
72 
We plan to assess feasibility and efficacy of establishing a virtual diabetes clinic with a focus on 
73 
introduction and training related to use of CGM technology and ongoing CGM use to minimize 
74 
such rate-limiting factors as geography, cost and access to specialty care. The virtual diabetes 
75 
clinic model will include a comprehensive care team with support for diabetes technology such 
76 
as CGM and decision support to align with current recommendations in diabetes care. Screening 
77 
for and access to diabetes-related mental health support will also be included. 
78 
1.2 Rationale 
79 
The objective of this study is to evaluate a virtual diabetes clinic model, for adults with either 
80 
T1D or T2D, that supports integration of CGM into diabetes self-management and evaluates use 
81 
of decision support technology within the virtual clinic model. The virtual diabetes clinic model 
82 
will also include mental health screening and support services, particularly for diabetes-related 
83 
issues. 
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1.3 Potential Risks and Benefits 
85 
1.3.1 Known Potential Risks 
86 
The fingerstick to collect the HbA1c sample could cause bruising and/or pain at the collection 
87 
site. 
88 
The CGM sensor may produce pain when it is inserted into the skin. There is a low risk for 
89 
developing a local skin infection at the site of the sensor needle placement. Itchiness, redness, 
90 
bleeding, and bruising at the insertion site may occur as well as local tape allergies. On rare 
91 
occasions, the sensor may break and leave a small portion of the sensor under the skin that may 
92 
cause redness, swelling, or pain at the insertion site. 
93 
There is a small risk of hypoglycemia when using CGM for insulin dosing if the CGM glucose 
94 
value is substantially higher than the true glucose level. There also is a small risk of 
95 
hyperglycemia if the CGM glucose is substantially lower than the true glucose. 
96 
There is a risk of breach of confidentiality. All data will be maintained in a secure database with 
97 
restricted access to help assure confidentiality. Data downloaded from diabetes devices will be 
98 
collected for the study. Some people may be uncomfortable with the researchers having such 
99 
detailed information about their daily diabetes habits. 
100 
There is the possibility that completion of questionnaires could make the participant feel 
101 
uncomfortable. 
102 
The study may include other risks that are unknown at this time. 
103 
1.3.2 Known Potential Benefits 
104 
It is likely that the participants will benefit from access to a virtual diabetes specialty clinic and 
105 
using CGM in the study. However, it is possible that participants will not directly benefit from 
106 
being a part of this study. 
107 
1.3.3 Risk Assessment 
108 
The protocol risk assessment for this study has been categorized as not greater than minimal risk. 
109 
1.4 General Considerations 
110 
The study is being conducted in compliance with the policies described in the study policies 
111 
document, with the ethical principles that have their origin in the Declaration of Helsinki, with 
112 
the protocol described herein, and with the standards of Good Clinical Practice (GCP). 
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 Study Enrollment and Baseline Data Collection 
114 
2.1 Participant Recruitment and Informed Consent 
115 
Adults (age >18 years) with type 1 diabetes or type 2 diabetes using insulin therapy (Tidepool- 
116 
compatible pump or injections) will be enrolled. Although the primary focus of the study is to 
117 
enroll non-CGM users, CGM users whose glycemic control is suboptimal can be enrolled. 
118 
Participation will be limited to U.S. residents in states where the virtual clinic is licensed; state 
119 
eligibility will be verified as part of screening. Potential participants may be recruited through 
120 
insurance providers, primary care networks, or health care providers. Potential participants also 
121 
may become aware of the study by other means, such as another study participant. 
122 
Up to 800 individuals may sign the informed consent form to initiate screening. Enrollment will 
123 
proceed with the goal of at least 300 participants initiating training for CGM use with the Virtual 
124 
Clinic. The goal will be to limit T2D enrollment to no more than 100. Recruitment efforts will be 
125 
focused on participants who receive diabetes care in a primary care setting rather than through an 
126 
endocrinologist, with a goal of having at least 225 who have not seen an endocrinologist in the 
127 
past six months. Eligible participants will be included without regard to gender, race, or 
128 
ethnicity. 
129 
The goal will be to include at least 50 participants <25 years of age and at least 50 participants 
130 
>65 years of age. 
131 
2.1.1 Informed Consent and Authorization Procedures 
132 
Individuals who indicate that they are interested will be directed to a website with information 
133 
about the study. Interested individuals will be able to communicate with study staff who can 
134 
answer questions about the study as part of the informed consent process. Individuals who want 
135 
to participate in the study will sign the Institutional Review Board (IRB) approved electronic 
136 
consent form. As part of the informed consent process, each participant will be asked to sign an 
137 
authorization for release of personal information. Participants will be asked to sign an addendum 
138 
consent for follow up after the first 6 months if they plan to continue use of CGM. 
139 
2.2 Participant Inclusion Criteria 
140 
Individuals must meet all the following inclusion criteria in order to be eligible to participate in 
141 
the study: 
142 
1. Age >18 years old 
143 
2. Diagnosis of type 1 diabetes or type 2 diabetes and using insulin therapy (at least 3 injections 
144 
of insulin per day or insulin pump that is compatible with Tidepool software) 
145 
Multiple daily injection (MDI) users must be willing to enter insulin dosing information 
146 
through an app 
147 
3. See a healthcare provider at least once a year 
148 
4. Resident of United States and plan to reside in the U.S. for the duration of the study 
149 
This requirement is due to virtual clinic license requirements and U.S. use restrictions for 
150 
some study software and devices. Not all U.S. states may be eligible for inclusion due to 
151 
virtual clinic license status. 
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5. Use either an Android or iOS smartphone that is compatible with app requirements that are 
153 
needed for the study 
154 
6. Access to a compatible computer with internet 
155 
7. Understand written and spoken English 
156 
8. Willing and able to follow the study procedures as instructed 
157 
2.3 Participant Exclusion Criteria 
158 
Individuals meeting any of the following exclusion criteria at baseline will be excluded from 
159 
study participation: 
160 
1. Current use of a closed loop system where an insulin pump and CGM share information and 
161 
insulin dose is automatically adjusted based on glucose reading 
162 
2. Current CGM use where Time in Range is ≥60.0% or Time <54% is ≤1.0%. 
163 
3. Current use of any off-label glucose-lowering medications for diabetes type (Example: T1D 
164 
use of non-insulin, anti-diabetic medications including SGLT2 inhibitors) 
165 
Use of such medications during the study will also be prohibited. 
166 
4. Females who are pregnant, intending to become pregnant, or breastfeeding during the study 
167 
5. Current renal dialysis or plan to begin renal dialysis during the study 
168 
6. Active cancer treatment 
169 
7. Extreme visual or hearing impairment that would impair ability to use real-time CGM 
170 
8. Known adhesive allergy/prior skin reaction or skin reaction identified during the blinded 
171 
CGM use phase that would preclude continued CGM use 
172 
9. Participation in a different diabetes management study during the study 
173 
10. Planned relocation to a state other than current state of residence during the study if virtual 
174 
clinic is not licensed in the new state. 
175 
Individuals working routinely in a state other than current state of residence in the next six 
176 
months are also ineligible if the virtual clinic is not licensed in that state. 
177 
2.4 Screening Procedures 
178 
Participants will be asked to confirm eligibility by completing a screening questionnaire. 
179 
Participants who pass screening will be asked to provide baseline data. Current CGM users will 
180 
also be asked to share their CGM data to confirm eligibility. If current data cannot be shared, 
181 
current CGM users will be asked to complete blinded CGM data collection.  Non-CGM users 
182 
will also be asked to complete blinded CGM data collection. Participants will be asked to submit 
183 
a baseline HbA1c sample 
184 
2.5 Collection of Baseline Data and Testing 
185 
After informed consent is signed, baseline data will be collected, including the following: 
186 
 Contact information 
187 
 Date of birth 
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 Demographics 
189 
 Height and weight 
190 
 Socio-economic information such as education, income, and insurance 
191 
 Name and contact information of healthcare provider for diabetes management 
192 
 Diabetes history, including diabetes duration, prior management, insulin delivery method, 
193 
meal bolus determination method, prior severe hypoglycemia (SH), prior diabetic 
194 
ketoacidosis (DKA) 
195 
 Medical history 
196 
 Medications, including but not limited to medications other than insulin being used for 
197 
glycemic control  
198 
 Prior CGM experience and knowledge, including why CGM is not used 
199 
 General health 
200 
 Questionnaires (see Chapter 4) 
201 
 Finger stick to measure HbA1c 
202 
 Blinded CGM Data Collection 
203 
2.5.1 HbA1c 
204 
HbA1c will be measured at a central laboratory. The participant will be sent a kit, which will 
205 
include a blood collection tube and shipping materials, to obtain a finger stick blood sample. The 
206 
sample will be returned to the lab in a prepaid mailer. Participants will be able to view their 
207 
HbA1c results through the study website. 
208 
2.6 CGM System 
209 
Participants will use the Dexcom G6, which is a commercially available CGM system. CGM 
210 
data will be shared with CDCES and study team members. 
211 
Other sensors that become FDA approved during the course of the study may be included as an 
212 
option for participants. If additional sensors are included, the participants will be given 
213 
information about CGM system options and will review the CGM systems with a study team 
214 
member. A recommendation may be provided for one of the systems based on discussion with 
215 
the participant, or there may be an indication that there is no specific recommendation. 
216 
Participants will be able to select the CGM system that they prefer, regardless of 
217 
recommendation. After a CGM system is selected, the participant may be asked why that system 
218 
was selected. 
219 
2.7 Blinded CGM 
220 
Non-CGM users will use a blinded CGM device for a single sensor wear period (usually at least 
221 
10 days) prior to CGM initiation. Current CGM users will be asked to use a blinded CGM device 
222 
for a single sensor wear period if their current CGM data cannot be successfully shared to 
223 
confirm eligibility. Study supplies required for blinded CGM data collection will be sent to the 
224 
participant by mail. An Android phone may be provided which is used as a receiver to collect 
225 
data from the blinded Dexcom G6 Pro. Current non-Dexcom CGM users, including pump users 
226 
with integrated CGM should continue to use their personal CGM for glucose management. 
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A virtual clinic team member will be available to answer questions about blinded CGM use. The 
228 
participants will not be able to see the glucose values and will be expected to follow their normal 
229 
diabetes management practice during this blinded CGM use period. The goal will be to obtain 
230 
ten days of blinded data. Participants may be asked to use a blinded CGM for an additional 
231 
sensor wear period if enough CGM data are not available to establish baseline comparator data. 
232 
Participants will be dropped from the study if blinded data cannot be obtained. Participants who 
233 
have a serious skin reaction to the sensor during blinded CGM wear that precludes continued use 
234 
of a sensor will be dropped. If additional FDA-approved CGM options are available for use in 
235 
this study, the participant may be offered the opportunity to try the other CGM system; in this 
236 
case blinded data collection would be repeated with another system. 
237 
2.8 Psychosocial Screening Questionnaires  
238 
Separate from the patient-reported outcome questionnaires, psychosocial screening 
239 
questionnaires are administered to study participants 4 times during the study: as part of baseline 
240 
data collection and 1, 2, and 3 months after unblinded CGM initiation. These screening 
241 
questionnaires are validated tools to evaluate depression, diabetes distress, and hypoglycemia 
242 
fears. Questionnaire administration is repeated to ensure that the virtual clinic team delivering 
243 
diabetes care is aware of any mental health issues that may make diabetes management harder 
244 
for the study participant. An elevated score on any of these questionnaires prompts an automated 
245 
alert to the virtual clinic team (See section 3.2).
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 Study Procedures and Data Collection 
247 
3.1 Overview 
248 
Training and data collection for the study will be completed remotely. Study supplies will be sent 
249 
to the participant by mail. Participants will be followed for up to 12 months or until they 
250 
discontinue CGM use. After initial CGM training has been completed, participants will continue 
251 
to be followed by the virtual clinic team for six months. After the initial six months of follow up, 
252 
participants who decide to continue to use CGM will be asked to extend follow up for an 
253 
additional 6 months and complete questionnaires, submit HbA1c samples, and share CGM data. 
254 
During the extended follow up phase, participants will be able to contact the virtual clinic with 
255 
questions or to request assistance as needed. 
256 
3.2 Virtual Clinic Team Interactions with Study Participant 
257 
Each participant will be assigned to work with virtual clinic team members who are able to 
258 
provide clinical care for diabetes management in the state where the participant resides. The 
259 
virtual clinic team members will teach participants to use and incorporate CGM into self-
260 
management practices. Mental health service support options for diabetes-related mental health 
261 
issues will be discussed as needed. 
262 
The virtual clinic team will assist with initiation of CGM, as needed, after CGM supplies are 
263 
received and will provide additional training after approximately one week of CGM use, and 
264 
after approximately three weeks of CGM use. Virtual clinic team members will check in with 
265 
participants during study follow up to review CGM data and recommendations related to 
266 
diabetes management, and additional virtual visits may be scheduled. Contact with a virtual 
267 
clinic team member may be requested by the participant at any time. 
268 
In addition, the virtual clinical team member will follow up with the study participant if there is 
269 
an elevated score on the psychosocial screening questionnaires (section 2.8). The virtual clinic 
270 
team will follow their internal processes for diabetes related mental health services support. 
271 
Participants may be offered the opportunity to work with a behavioral health coach from the 
272 
virtual clinic team at no cost. Follow up communication with a personal healthcare provider is at 
273 
the discretion of the virtual clinic for any issues which may require additional support. 
274 
The virtual clinic team member(s) may interact with the participant through texts, emails, phone 
275 
calls and/or virtual training sessions. Phone calls may be recorded. Additional mobile 
276 
applications may be required to facilitate communications between participant and virtual clinic 
277 
team member(s) depending on program enrollment. 
278 
3.2.1 Virtual Clinic Team Interactions with Personal Healthcare Provider 
279 
Communications will be provided to the health care provider whom the participant designates for 
280 
diabetes management, so that the provider is aware of the participant’s study participation and of 
281 
information related to care or treatment (See section 3.5.2). 
282 
3.3 CGM Initiation (Unblinded Use) 
283 
CGM supplies will be sent to the participant by mail. Device user manuals will be provided 
284 
along with study instructions. The study website will include a resources page which may 
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include device user manuals, study instructions and tutorials, and links to standard of care 
286 
diabetes-related educational information recommended by the study team. Live webinars may be 
287 
available for those who want to receive additional education about diabetes management and use 
288 
of CGM technology. 
289 
A virtual training session will be arranged with the participant’s virtual clinic team member to 
290 
answer questions regarding CGM set up, sensor insertion, alerts and alarms, uploading data, and 
291 
visualizing data. 
292 
3.4 CGM Use and Data Interpretation 
293 
After the initial training to initiate CGM use, participants will receive additional training on how 
294 
to use data visualization tools and how to use the CGM data to make self-management changes 
295 
in insulin dosing, meals, exercise, etc. The training approach may vary by participants’ age 
296 
and/or comfort with technology. 
297 
3.5 Insulin Dose Changes 
298 
If the virtual clinic team believes that changes in insulin type or dosing should be considered, 
299 
they will work with the participant to implement any such changes. 
300 
3.5.1 Decision Support 
301 
Decision support tools, which include use of a mobile application, may be used, if available, to 
302 
provide the virtual clinic team with potential recommendations regarding insulin use. The virtual 
303 
clinic team will review all data, including any available decision support recommendations, 
304 
before making recommendations. Use of decision support for T1D is approved for 
305 
recommendations to providers. Use for T2D is investigational. For both T1D and T2D, use of 
306 
decision support would be classified as a Non-Significant Risk as the decision support 
307 
recommendation is made to the provider and does not replace virtual clinic team review of all 
308 
available CGM and insulin data when considering management decisions. 
309 
3.5.2 Personal Healthcare Provider Notification 
310 
The health care provider whom the participant designates for diabetes management will be 
311 
informed of insulin dose and other medication changes. 
312 
3.6 Follow-up Data Collection 
313 
Data will be collected throughout study follow up and will include information related to 
314 
diabetes management, psychosocial outcomes, adverse event and device issues, patient-related 
315 
outcomes and questionnaires, HbA1c measurement, and upload of device data. 
316 
3.6.1 HbA1c 
317 
HbA1c will be collected at approximately 13, 26, 39, and 52 weeks and measured at a central 
318 
laboratory. A kit, which will include a blood collection tube and shipping materials, will be sent 
319 
to the participant to obtain a fingerstick blood sample and return the sample to the lab. 
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3.7 Data Uploads 
321 
Instructions for downloads and data sharing from diabetes-related care devices and applications 
322 
used for the study will be reviewed with each participant as part of their training. 
323 
3.8 Insulin Delivery and Collection of Insulin Data 
324 
Participants will use their own insulin during the study. If the participant uses an insulin pump, 
325 
training will include uploading (or linking) of these devices.  
326 
MDI users with a compatible insulin pen may be given a Biocorp Mallya (Mallya) device to use 
327 
during the study that automatically logs insulin dose. Mallya is a data collection device that 
328 
automatically captures data such as date of injection, time of injection, insulin type, and dose. 
329 
Mallya attaches directly to the insulin pen and does not alter how the pen is used. Mallya is 
330 
intended for data collection purposes only, with minimal information communicated to the 
331 
participant via the app or device. Mallya is an investigational device, and it is classified as a 
332 
Non-Significant Risk device by the Sponsor. 
333 
An app that is needed to transfer data from the device used to log insulin dose will be installed 
334 
on the participant’s personal smartphone. Participants will be trained on use of the device and 
335 
app as needed. If a device that automatically logs insulin dose is not available, the participant 
336 
may be asked to enter insulin doses directly through an app. 
 
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 Questionnaires 
338 
Questionnaires are completed by all participants on the study website. The responses to the 
339 
outcome surveys are not monitored in real-time. The procedures for administration are described 
340 
in the study procedures manual. 
341 
Measure 
DESCRIPTION 
Patient Health 
Questionnaire- 8 
8-item survey to evaluate depression-related symptoms; 3 minutes to 
complete 
Diabetes Distress 
Scale (Management 
Distress Items) 
17-item management burden scale to measure the degree of distress 
related to diabetes; 4 minutes to complete. 
Fear of 
Hypoglycemia 
(Worry) 
6- item survey to measure concerns about low blood sugar; 2 minutes 
to complete 
CDC Healthy Days 
4 questions developed by the CDC to obtain a general assessment of 
physical and mental health; 2 minutes to complete 
Hypoglycemia 
Confidence 
Presents 8 common situations where hypoglycemia occurs and 
evaluates level of confidence of how it can be managed in those 
situations; 4 minutes to complete. 
Diabetes Technology 
Attitudes 
5-item survey to measure perceptions about the benefits of diabetes 
technology and devices; 2 minutes to complete. 
Glucose Monitoring 
Satisfaction 
15-item survey to evaluate treatment satisfaction/burden; 4 minutes to 
complete. 
Sleep 
1-item sleep survey that measures quality of sleep; 1 minute to 
complete 
Benefits and Burdens 
of CGM 
16 items per section with 2 sections that list situations (e.g. ability to 
share data, glycemic events, physical activity) and designation of 
whether they are barriers or benefits; 4 minutes to complete. 
CGM 
Discontinuation 
3-item survey; participants who discontinue CGM will be asked to 
complete this. 
Participants may also be asked to answer questions, which have been approved by the IRB, 
342 
regarding their participation experience.
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 Miscellaneous Considerations 
344 
5.1 Adverse Events 
345 
Participants will be asked to complete questionnaires to report events that have occurred. For 
346 
each event reported, the participant will be asked if the event could have been related to the use 
347 
of CGM. 
348 
If there is no response, the participant may be contacted again to encourage questionnaire 
349 
completion. 
350 
Participants will be asked to report the following events: 
351 
● 
Severe hypoglycemia 
352 
o Reportable events will be defined as hypoglycemia during which the participant was 
353 
impaired cognitively to the point that he/she was unable to treat himself/herself, was 
354 
unable to verbalize his/her needs, was incoherent, disoriented, and/or combative, or 
355 
experienced seizure or loss of consciousness. 
356 
● 
DKA 
357 
o The participant will be asked if he/she was seen at a health care facility and/or 
358 
hospitalized and what the ketone level was if known. 
359 
● 
Hospitalizations 
360 
Adverse event data reported to virtual clinic team members and study staff will be collected.  
361 
5.2 Device Issues 
362 
Participants will also be asked to report the following device issues: 
363 
● 
Device-related events with potential impact on participant safety 
364 
o Skin reactions at the sensor site will be reported as adverse events if they are 
365 
classified as severe and/or required treatment. 
366 
5.3 Study Costs 
367 
CGM supplies will be provided for the first six months of the study. Participants will be able to 
368 
keep the provided CGM supplies after follow up has ended. Participants who plan to continue 
369 
use of CGM after 6 months will need to work with their insurance provider to obtain approval 
370 
for CGM. 
371 
Costs of standard medical care for diabetes that would occur even if the participant were not in 
372 
this study, including insulin, will be the participant’s responsibility. 
373 
5.4 Participant Compensation 
374 
Participant compensation will be specified in the informed consent form. 
375 
5.5 Participant Withdrawal 
376 
Participation in the study is voluntary, and a participant may withdraw at any time. The reason 
377 
for withdrawal will be collected. Additionally, at the time of withdrawal, the participant will be 
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asked to complete device downloads and questionnaires. For participants who withdraw, their 
379 
data will be used up until the time of withdrawal. 
380 
Participants who do not complete baseline procedures in a timely fashion or are noncompliant 
381 
with respect to the protocol may be withdrawn. 
382 
5.5.1 Pregnancy 
383 
If pregnancy occurs, the participant will be withdrawn from the study. 
384 
5.6 Contact Information 
385 
Contact information for each participant, including name, email address, mobile number, and 
386 
mailing address will be provided to the coordinating center, the Jaeb Center for Health Research 
387 
in Tampa, FL. Permission to obtain such information will be included in the Informed Consent 
388 
Form. The contact information for the study will be maintained in a secure database and will be 
389 
maintained separately from study data. 
390 
Contact information is necessary for shipment of study supplies, set up of certain apps needed for 
391 
the study on the participant’s personal smartphone, and participant payments. Contact 
392 
information will be used by virtual clinic team members for training and follow up. Participants 
393 
will receive reminders via text, email, or phone to complete questionnaires or submit study data. 
394 
Mobile number will be shared with parties involved in processing of data if the mobile number is 
395 
required to send automated text reminders to minimize missing data. 
396 
Communications will be provided to a health care provider designated by the participant. 
397 
5.6.1 Personal Healthcare Provider Information 
398 
Participants will be asked to provide the contact information of a health care provider that they 
399 
designate for their diabetes management. Provider information is necessary so that the provider 
400 
can be made aware of the participant’s study participation and of information related to care or 
401 
treatment. Permission for communication to the designated health care provider will be included 
402 
in the Informed Consent Form. 
403 
5.7 Confidentiality 
404 
For security purposes, participants will be assigned an identifier that will be used instead of their 
405 
name. Protected health information gathered for this study will be shared with the JCHR 
406 
coordinating center in Tampa, FL, virtual clinic and study team members involved with 
407 
participant training and review of CGM data, participating institutions and investigators in the 
408 
research study, and parties involved in collecting and processing of data in accordance with the 
409 
terms of the study contracts. Participant calls with the virtual team members may be recorded. 
410 
The informed consent form will specify entities that will have access to or receive data. 
411 
No identifiable health information of an enrolled participant will be released by the coordinating 
412 
center, except as described above. 
413 
5.8 Quality Assurance and Monitoring 
414 
Designated personnel from the coordinating center will be responsible for maintaining quality 
415 
assurance and quality control systems to ensure that the trial is conducted, and that data are 
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generated, documented and reported in compliance with the protocol, GCP and the applicable 
417 
regulatory requirements. 
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 Statistical Considerations 
419 
6.1 Statistical and Analysis Plan 
420 
The approach to sample size and statistical analyses are summarized below. A Statistical 
421 
Analysis Plan (SAP) will be written and finalized prior to the completion of the study. The 
422 
analysis plan synopsis in this chapter contains the framework of the anticipated final SAP. The 
423 
SAP will describe the analyses to be performed for the primary manuscript. 
424 
6.2 Sample Size 
425 
The goal for the study is to include at least 300 participants who initiate training for CGM. This 
426 
is a convenience sample and not based on statistical principles. 
427 
6.3 Outcome Measures 
428 
The following outcome measures will be stratified by type of diabetes. 
429 
Efficacy Outcomes: 
430 
 HbA1c 
431 
 CGM use 
432 
 Mean of sensor glucose levels 
433 
 Percentage of time spent with sensor glucose levels <54 and <70 mg/dL 
434 
 Percentage of time spent with sensor glucose levels >180 and >250 mg/dL 
435 
 Percentage of time spent with sensor glucose levels in the target range (70-180 mg/dL) 
436 
 Glycemic variability measured by the coefficient of variation 
437 
 Insulin metrics 
438 
 Questionnaire scores (and their corresponding subscales) 
439 
 Psychosocial metrics 
440 
 Healthcare utilization metrics 
441 
 
442 
CGM, HbA1c, and questionnaires outcomes will be evaluated at all time points they are 
443 
collected.  
444 
 
445 
Safety Outcomes: Severe Hypoglycemia and DKA events, and hospitalizations 
446 
6.4 Description of Statistical Methods 
447 
6.4.1 Analysis Cohorts 
448 
All subjects enrolled in the study who initiate the CGM and have a minimum amount of data as 
449 
defined in the SAP will be included in the tabulations of   baseline and the efficacy analyses. All 
450 
subjects enrolled in this study will be included in the safety analyses. 
451 
6.5 Analysis of Efficacy Outcomes 
452 
CGM metrics and HbA1c will be calculated and summarized at 13, 26, 39, and 52 weeks. 
453 
Summary statistics for questionnaires will be provided at all time points when they are collected. 
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A linear mixed model with a random subject effect will be used to assess whether the change 
455 
from baseline significantly differs from zero. If values are highly skewed, then the winsorized 
456 
mean will be tested or a transformation utilized. A complete-case analysis using a paired t-test or 
457 
Wilcoxon signed rank test will also be assessed. 
458 
6.6 Subgroup Analyses 
459 
Subgroup analyses for HbA1c and selected CGM outcomes will be performed by baseline 
460 
HbA1c group, insulin delivery modality, age, healthcare provider (endocrinologist or primary 
461 
care provider), and various participant characteristics as described in the SAP. 
462 
6.7 Safety Analyses 
463 
All adverse events that occur post enrollment will be listed in a table. Additionally, each of the 
464 
following safety metrics will be tabulated for reported SH and DKA events, hospitalizations and 
465 
emergency room visits: 
466 
 Number of subjects with ≥1 event 
467 
 Number of events per subject 
468 
 Incidence rate per 100 person-years 
469 
6.8 Baseline Descriptive Statistics 
470 
Baseline demographic and clinical characteristics of the cohort of all subjects who initiate the 
471 
CGM will be summarized in a table. 
472 
6.9 Multiple Comparisons/Multiplicity 
473 
No adjustments for multiple comparisons will be made. 
474 
6.10 Additional Analyses 
475 
Several additional analyses will be performed in this study. These will include the following: 
476 
 Tabulations of CGM glycemia and CGM use by month and comparing the first 26 weeks 
477 
and last 26 weeks of the study (overall and within subgroups) 
478 
 Tabulations of CGM glycemia by time of day 
479 
 Tabulations of the number of participant contacts with the virtual clinic 
480 
 Bivariate relationship between questionnaires and glycemic metrics following CGM 
481 
initiation
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 Ethics/Protection of Human Participants 
483 
7.1 Ethical Standard 
484 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
485 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 
486 
21 CFR Part 56, and/or the ICH E6. 
487 
7.2 Institutional Review Boards 
488 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
489 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
490 
form must be obtained before any participant is enrolled. Any amendment to the protocol will 
491 
require review and approval by the IRB before the changes are implemented to the study. All 
492 
changes to the consent form will be IRB approved; a determination will be made regarding 
493 
whether previously consented participants need to be re-consented. 
494 
7.3 Informed Consent Process 
495 
7.3.1 Consent Procedures and Documentation 
496 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
497 
the study and continues throughout the individual’s study participation. Individuals who indicate 
498 
that they are interested in study participation will be directed to a website with information about 
499 
the study. Interested individuals will be able to have a live chat or arrange for a phone call to 
500 
answer questions about the study as part of the informed consent process. Participants who want 
501 
to participate in the study will sign the IRB-approved electronic consent form. 
502 
The participants should have the opportunity to discuss the study with their surrogates or think 
503 
about it prior to agreeing to participate. The participant will sign the informed consent document 
504 
prior to any procedures being done specifically for the study. The participant may withdraw 
505 
consent at any time throughout the course of the study. The participant will be able to print a 
506 
copy of the informed consent document for their records. The rights and welfare of the 
507 
participants will be protected by emphasizing to them that the quality of their medical care will 
508 
not be adversely affected if they decline to participate in this study. 
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 References 
510 
1. 
Acciaroli G, Vettoretti M, Facchinetti A, Sparacino G. Toward calibration-free 
511 
continuous glucose monitoring sensors: Bayesian calibration approach applied to next-
512 
generation Dexcom technology. Diabetes Technology & Therapeutics. 2018;20(1):59-67. 
513 
2. 
Bailey TS, Chang A, Christiansen M. Clinical accuracy of a continuous glucose 
514 
monitoring system with an advanced algorithm. J Diabetes Sci Technol. 2015;9(2):209-
515 
214. 
516 
3. 
Beck R, Riddlesworth T, Ruedy K, et al. Effect of continuous glucose monitoring on 
517 
glycemic control in adults with Type 1 Diabetes using insulin injections: The DIAMOND 
518 
randomized clinical trial. JAMA. 2017;317(4):371-378. 
519 
4. 
Bergenstal RM, Tamborlane WV, Ahmann A, et al. Effectiveness of sensor-augmented 
520 
insulin-pump therapy in Type 1 Diabetes. New England Journal of Medicine. 
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2010;363(4):311-320. 
522 
5. 
Bolinder J, Antuna R, Geelhoed-Duijvestijn P, Kröger J, Weitgasser R. Novel glucose-
523 
sensing technology and hypoglycaemia in Type 1 Diabetes: A multicentre, non-masked, 
524 
randomised controlled trial. Lancet. 2016;388(10057):2254-2263. 
525 
6. 
Heinemann L, Freckmann G, Ehrmann D, et al. Real-time continuous glucose monitoring 
526 
in adults with Type 1 Diabetes and impaired hypoglycaemia awareness or severe 
527 
hypoglycaemia treated with multiple daily insulin injections (HypoDE): A multicentre, 
528 
randomised controlled trial. Lancet. 2018;391(10128):1367-1377. 
529 
7. 
Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, 
530 
Beck R, Hirsch I, et al. The effect of continuous glucose monitoring in well-controlled 
531 
Type 1 Diabetes. Diabetes Care. 2009;32:1378-1383. 
532 
8. 
Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, 
533 
Tamborlane W, Beck R, et al. Continuous glucose monitoring and intensive treatment of 
534 
Type 1 Diabetes. New England Journal of Medicine. 2008;359(14):1464-1476. 
535 
9. 
Lind M, Polonsky W, Hirsch I, et al. Continuous glucose monitoring vs conventional 
536 
therapy for glycemic control in adults with Type 1 Diabetes treated with multiple daily 
537 
insulin injections: The GOLD randomized clinical trial JAMA. 2017;317(4):379-387. 
538 
10. 
Little S, Leelarathna L, Walkinshaw E, et al. Recovery of hypoglycemia awareness in 
539 
long-standing Type 1 Diabetes: A multicenter, 2 x 2 factorial, randomized controlled trial 
540 
comparing insulin pump with multiple daily injections and continuous with conventional 
541 
glucose self-monitoring (HypoCOMPaSS). Diabetes Care. 2014;37:2114-2122. 
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