PROMISE Study: A Prospective, Multicenter Evaluation of Accuracy and Safety of an Implantable Continuous Glucose Sensor Lasting up to 180 Days
Phase: NA
Conditions: Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Sponsor: Senseonics, Inc.

Cover Page 
Title: PROMISE Study: A Prospective, Multicenter Evaluation 
of Accuracy and Safety of an Implantable Continuous Glucose Sensor 
Lasting up to 180 Days 
NCT Number: 03808376 
Document Type: Protocol 
Document Date: April 14, 2020 

Confidential
Signature Manifest
Document Number: CTP-0036
Revision: 09
Title: PROMISE Study
Effective Date: 14 Apr 2020
All dates and times are in Eastern Standard Time.
PROMISE Study
Approval
Name/Signature
Title
Date
Meaning/Reason
Margaret Lewis (MLEWIS)
Director of Clinical Ops
13 Apr 2020, 06:08:27 PM
Approved
Katherine Tweden (KTWEDEN)
VP, Clinical Sciences
13 Apr 2020, 06:21:09 PM
Approved
Colleen Mdingi (CMDINGI)
Manager, Clinical Data Mgmt.
14 Apr 2020, 10:11:00 AM
Approved
Quality Approval
Name/Signature
Title
Date
Meaning/Reason
Dawit Belete (DBELETE)
Director, Quality Sciences
14 Apr 2020, 10:20:42 AM
Approved
Quick Approval
Approve Now
Name/Signature
Title
Date
Meaning/Reason
Melissa Leygan (MLEYGAN)
Sr. Doc. Control Specialist
14 Apr 2020, 03:25:55 PM
Approved

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
Title of Protocol: PROMISE Study: A Prospective, Multicenter Evaluation 
of Accuracy and Safety of an Implantable Continuous Glucose Sensor 
Lasting up to 180 Days
Protocol Number: CTP-0036
Protocol Version: 9
Senseonics, Incorporated
20451 Seneca Meadows Parkway
Germantown, MD 20876
USA
Confidential Information
Property of Senseonics, Incorporated ®
This Clinical Protocol contains confidential information for use by the investigators and their 
designated representatives participating in this clinical investigation. It must be held as
confidential and maintained in a secure location.  It must not be copied or made available for
review by any unauthorized person or firm.

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
SUMMARY OF CHANGES
ProtocolVersion
Change Description
01
Initial release
02
Additional visits on days 7, 14 and 22. Added cohorts A and B to 
determine which subjects attend those visits. Changed sampling 
duration from 6.5 to 8 hours. Increased number of subjects with 2 
sensors. Decreased total number of subjects inserted from 125 to 124. 
Added safety criteria for withdrawing subjects and stopping the study.
03
Update to subject withdrawal criteria (7.6.4) and disqualification for 
glucose challenge (4.3.4) for subjects who develop DKA or severe 
hypoglycemia
04
Increased number of subjects inserted from 124 to 160. Increased 
possible sites from 8 to 15. Modified visit schedule. Added 
randomization for (1) day 1 visits to occur at 1-12 or 12-24 hours after
first CGM glucose value, (2) subjects to complete either day 7 or day 14 
visits. Added enrollment targets. Accuracy visit lengths increased. Visit 
windows increased. Screening may occur up to 45 days prior to 
insertion. 
05
Day 1 subjects to be randomized to one of three, 8 hour sampling (10 
hour accuracy visits), Sampling decreased to 8 hours for all visits for all 
subjects except for Day 180 visit which has 10 hour sampling.  
Glucocorticoids use allowed expect for topical over sensor. Allowed for 
repeat of screening if insertion cannot be scheduled within window.
During the study the primary system may go into a “blinded mode” 
(called Clinical Mode by the device).
06
Updated sections 3.2.2, 7.6.4 and 8.6 to removed MRI scan from the
study exclusion criteria, subject withdrawal criteria, and as possible 
interaction with concomitant medical treatment; updated sections 
4.2.8, 4.2.9, 4.3 and 4.3.7 to clarify CGM system calibration per system 
requirements during accuracy visits; updated section 4.3.7.2 to clarify
that CGM System calibration should be performed using SMBG values 
from the study-supplied meter (Contour Next One meter).

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
07
Increased sample size from 180 enrolled to 210 enrolled. Increased 
number of subjects inserted from 160 to 180. Updated study duration 
to reflect timelines for additional enrollment.
08
Increased wear period for subjects with a secondary sensor to one year 
and added an additional primary sensor cycle for observational 
purposes. Added 3 accuracy visits in follow up phase at 240, 300 and 
365 days.
09
Removed Accuracy visits at D240, D300, and D360. Adjusted for site 
visits to be for device download and safety review.

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
PROTOCOL SIGNATURE PAGE (Sponsor)
PROMISE Clinical Study Protocol (CTP-0036)
                  Signed and Dated Electronically 
______________________________________ 
    _________________________
Katherine Tweden, PhD, Vice President, Clinical Sciences
Date
   
                  
____________________________________________                         ____________________________
Chris Mullin, MS, NAMSA Statistical Consultant
   Date
*Updates to Rev 09 do not impact statistical methods; review by statistician not required

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
PROTOCOL SIGNATURE PAGE
Investigator’s statement
I agree to conduct this clinical investigation in accordance with the design and specific
provisions of this protocol and all applicable regulatory requirements. Modifications to the 
clinical investigation are acceptable only with a mutually agreed upon protocol
amendment as approved by the sponsor, regulatory bodies and Institutional Review Board/
Ethics Committee. I agree to await Institutional Review Board/ Ethics Committee approval
of the protocol, informed consent, and sponsor approval before initiating the study, and to
obtain consent from subjects prior to their enrollment in the study. I agree to collect and
record data as required by the protocol and case report forms, and to maintain study
documents for the period of time required.
Confidential
This document contains confidential information belonging to Senseonics, Inc. Except as
may be otherwise agreed to in writing, by accepting or reviewing these materials, I agree to 
hold such information in confidence and not to disclose it to others (except where required
by applicable law), nor use it for unauthorized purposes.
Investigator’s signature
Date of signature

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
SYNOPSIS
Title of Protocol
PROMISE Study: A Prospective, Multicenter Evaluation of Accuracy 
and Safety of an Implantable Continuous Glucose Sensor Lasting 
up to 180 Days  
Sponsor
Senseonics, Inc.
Investigational Device
Eversense® 180 Continuous Glucose Monitoring (CGM) System
(the “System”)
Reference
Instrument
Reference Glucose Analyzer (bedside, YSI 2300 STAT PLUS®
Glucose and Lactate Analyzer, Yellow Springs Instruments,
Yellow Springs, OH, USA).
Calibration
Standard
FDA-cleared Blood Glucose Meter (Subject SMBG Meter)
Study Purpose
The purpose of this clinical investigation is to evaluate the accuracy
of the Eversense® Continuous Glucose Monitoring System
(Eversense® 180 CGM System) measurements when compared with
reference standard measurements up to 180 days of sensor use. 
The investigation will also evaluate safety of the Eversense® 180 
CGM System usage.
Target Indication for
Use
The Eversense® 180 CGM System is a glucose monitoring device
intended to continually measure interstitial fluid glucose levels
in individuals with diabetes for the operating life of the sensor.
The Eversense® 180 CGM System is intended to be used:
!
To provide real-time glucose readings directly to the user.
!
To provide glucose trend information.
!
To provide alerts for the detection and prediction of
episodes of low blood glucose (hypoglycemia) and high
blood glucose (hyperglycemia).
Study Design Summary
This is a prospective, multi-center study, enrolling adult 
subjects with diabetes mellitus in the United States at up to 15
sites. The investigation will include both clinic visits and home
use of the Eversense® 180 CGM System. Subjects will have one
Sensor inserted in the upper arm by trained Investigators.  A 
minimum of 80 subjects will have two sensors inserted. The
accuracy of the system will be evaluated during clinic visits,
comparing CGM glucose with laboratory reference values. For
qualifying subjects, during the clinic visits, there are planned
hyperglycemia and hypoglycemia challenges.  All diabetes care
decisions will be based on blood glucose values, rather than
CGM results. 

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
Random assignment will be used to obtain sufficient numbers 
of subjects for each shift of the day 1 accuracy visit (hours 1-8
vs. hours 9-16 vs. hours 17-24 after first CGM glucose value) 
and for the timing of the Visit 4 accuracy assessment (day 7 or 
14). Each randomization (2 total, with 3 conditions for day 1 
and 2 conditions for days 7/14) will be independent. 
Randomization is only intended to ensure adequate numbers 
of subjects within conditions and is not intended to form the 
basis for formal statistical comparisons. 
Visit Schedule:
!
Screening Visit (Visit 1). Following informed consent
process, screening evaluation will determine subject
eligibility for enrollment. Visit lasts approximately 2
hours. Visit includes screening medical and diabetes
history, examination and laboratoryassessments. 
Baseline blood draw for HbA1c and Quality of Life 
Questionnaire will be done. At this visit subjects will be 
randomized to determine the subsequent follow-up 
visit schedule.
!
Day 0 (+0-45 days from screening) Sensor Insertion
Visit (Visit 2). Sensors will   be inserted by Investigator
in the upper arms.   Subjects will receive one sensor or
two sensors (one in each arm). In two sensor subjects,
one sensor will be designated the secondary system and 
will not require calibration. This system will have the 
ability to collect and log data only and will not display 
glucose.  Subject receives training on study and
devices.
Sensor Accuracy Visits. The following visits include Sensor
accuracy assessment with reference laboratory glucose
comparison, Sensor calibration with blood glucose (BG) meter, and
safety assessments. Blood draws to measure HbA1c will be done 
at the 90 and 180-day visits.
!
Day 1 – hours 1-8 (± 0 Day) Visit 3A.  Visit lasts
approximately 11 hours (Day 1 Early Shift Group). 
!
Day 1 – hours 9-16 (± 0 Day) Visit 3B.  Visit lasts 
approximately 10 hours (Day 1 Middle Shift Group). 

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
!
Day 1 – hours 17-24 (± 0 Day) Visit 3C.  Visit lasts 
approximately 10 hours (Day 1 Late Shift Group). 
!
Day 7 (± 1 Day) Visit 4A.  Visit lasts approximately 10
hours (Day 7 Accuracy Group). 
!
Day 14 (± 1 Day) Visit 4B.  Visit lasts approximately 10
hours (Day 14 Accuracy Group). 
!
Day 22 (± 1 Day) Visit 5.  Visit lasts approximately 10
hours (all subjects).
!
Day 30 (-3/+7 Days) Visit 6. Visit lasts approximately 
10 hours (all subjects). 
!
Day 60 (-7/+7 Days) Visit 7. Visit lasting approximately 
10 hours (all subjects). 
!
Day 90 (-7/+7 Days) Visit 8. Visit lasting approximately 
10 hours (all subjects). 
!
Day 120 (-7/+7 Days) Visit 9. Visit lasting 
approximately 10 hours. 
!
Day 150 (-7/+7 Days) Visit 10. Visit lasting 
approximately 10 hours.
!
Day 180 (-3/+2 Days) Visit 11. Visit lasting 
approximately 12 hours.
A subset of subjects inserted with 2 sensors may be requested to 
continue participation in the study after Day 180. Those subjects 
will not participate in any additional accuracy visits. Subjects will 
return to the clinic for device downloads and  safety assessments 
for Adverse Events approximately every 2 months A blood draw 
will be done at the 365-day visit to measure HbA1c.
!
Day 240 (±7 Days) Visit 13. Visit lasting approximately 1
hours. 
!
Day 300 (±7Days) Visit 14. Visit lasting approximately 1 hours.

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
!
Day 365 (+7 Days) Visit 15. Visit lasting approximately 1 
hours.
Following the day 180 accuracy visit, Sensors are removed at end 
of visit or within 7 days of the day 180 visit. For subjects with two 
sensors, only the primary sensor will be removed following the 
day 180 visit. At the removal visit, a new primary sensor will be 
inserted for an additional 180 days of wear. Both sensors will be 
removed following the 365 clinic visit (+7 days). Blood draws for 
HbA1c and quality of life questionnaires will be conducted at the 
removal visits. In the case that a sensor enters clinical mode prior 
to removal, subjects will be asked to complete the quality of life 
questionnaires at the visit following confirmation of Clinical 
Mode. 
!
Follow-up Visit: Visit 12. Sensor Site Assessment is 
performed approximately 10 days (-3/+7 days) after
Sensor removal and insertion, as applicable, to
assess Sensor sites. At this visit, if there is a
concern by investigator about healing of sensor
site, subject will return in approximately 10 days
and followed until resolution.
Visit 16. Sensor Site Assessment is performed 
approximately 10 days (-3/+7 days) after final 
sensor removals to assess Sensor sites. At this visit,
if there is a concern by investigator about healing
of sensor site, subject will return in approximately
10 days and followed until resolution.
Home Use: Subjects will follow their usual diabetes care routine
as per their medical team recommendations while wearing the
System. All diabetes management decisions by the subject and
health care team will be made based on standard of care with
blood glucose monitoring, and not based on Eversense® 180
CGM glucose values. Subjects will be advised to wear the
Transmitter over the Sensor for data collection, except during
transmitter charging.
Subjects will calibrate the CGM using the study-provided Subject 
SMBG Meter as prompted by the CGM and according to
Instructions for Use. Subjects will use the same study-provided
BG meter for monitoring their diabetes care, and this meter will
be downloaded during the clinic visits. Subjects will be

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
requested to check the BG meter glucose for all diabetes care 
decisions approximately 7 times per day. Subjects will be 
monitored for compliance to a minimum of 4 SMBG readings per 
day including at least 1 pre-prandial and one bedtime reading.
All SMBG readings will be requested to be entered into the 
Eversense mobile app as events.
The cohort of subjects that are participating in the PROMISE 
extension to 365 days will have the accuracy of their new 180 
day sensor monitored approximately every 2 weeks to ensure 
that the distribution of performance for that cohort is consistent 
with what was seen in previous clinical studies. If the 
performance is not consistent with what has been seen in 
previous clinical studies, the study subject’s SMBG entry 
compliance will be monitored on a daily basis until performance 
comes back within the distribution. If performance is not 
restored to the expected distribution within 2 weeks, the 180-
day sensor will be placed in blinded Clinical Mode for the 
remainder of the study. The subject will be blinded to glucose 
values, alerts and alarms.
Clinic Visits: Blood samples, meter BG, and Sensor glucose
values will be collected. Diabetes care decisions during the visit
will be made based on blood glucose determinations, rather 
than Eversense® 180 CGM System results.
During sampling periods, blood samples will be collected for 
glucose reference analysis approximately every 15 minutes and
more frequently (approximately every 5 minutes) during periods
of hypoglycemia and hyperglycemia as described in the
protocol.
Safety Assessments and Management
There will be trained staff and an emergency cart available at
the site at all times. Safety guidelines will be utilized for subject
care during periods of hyperglycemia (including monitoring
blood ketones) and hypoglycemia. A physician, PA or nurse 
practitioner will be available at all times during hypoglycemia and
hyperglycemiachallenges.

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
The sensor insertion site(s) will be assessed at each clinic visit.
A review and documentation of adverse events occurring in
the clinic and during home use will be on-going.
Laboratory tests will be performed as per protocol for safety
assessment. Additional details of the study design and safety
assessments and management are described in the protocol.
Blood draws for HbA1c measurements will be made at 
Screening, Day 90, Day 180, and Day 365 (Visits 1, 8, 11 & 15).  
Estimated Study
Duration of Study and
Subject Participation
Enrollment Period: Approximately 8 months
Individual Subject Participation: Approximately 8 months and 
up to 14 months for subjects with two sensors
Duration of Study: Approximately 18 months for the primary 
analysis and up to 26 months for the 365-day analysis group
Study Sites
Up to 15 investigative sites located in the United States.
Subject Population
The subject population consists of adult subjects with
diabetes mellitus. Based on sample size calculations,
approximately 210 adult subjects will be enrolled and 
approximately 180 will be inserted with the CGM Sensor in
the investigation. Subgroups based on diabetes type
(approximately 70% type 1), baseline HbA1c and age ranges 
will be targeted for enrollment.
Inclusion Criteria
Male and Female Subjects meeting all of the following
inclusion criteria will be included in this study:
1. Adult subjects, age ≥18 years
2. Clinically confirmed diagnosis of diabetes mellitus for ≥1
year
3. Subject has signed an informed consent form and is
willing to comply with protocol requirements
Subjects meeting any of the following exclusion criteria at the
time of screening will be excluded from this study:
1. History of unexplained severe hypoglycemia in the previous 6
months. Severe hypoglycemia is defined as hypoglycemia
resulting in loss of consciousness or seizure
2. History of diabetic ketoacidosis requiring emergency room
visit or hospitalization in the previous 6 months
3. Subjects with gastroparesis.
4. Female subjects of childbearing capacity (defined as not
surgically sterile or not menopausal for ≥1 year) who are
lactating or pregnant, intending to become pregnant, or
not practicing birth control during the course of the study.

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
Exclusion Criteria
5. A condition preventing or complicating the placement,
operation, or removal of the Sensor or wearing of
transmitter, including upper extremity deformities or skin
condition. 
6. Symptomatic coronary artery disease; unstable angina;
myocardial infarction, transient ischemic attack or stroke in
the past 6 months; uncontrolled hypertension (systolic>160
mm Hg or diastolic >100 mm Hg at time of screening);
current congestive heart failure; history of cardiac
arrhythmia (benign PACs and PVCs allowed). Subjects with 
asymptomatic coronary artery disease (e.g. CABG, stent 
placement or angioplasty) may participate if negative stress 
test within 1 year prior to screening and written clearance 
from Cardiologist documented.
7. Hematocrit <30% or >60% 
8. History of hepatitis B, hepatitis C, or HIV
9. Current treatment for a seizure disorder unless written
clearance by neurologist to participate in study
10. History of adrenal insufficiency
11. Currently receiving (or likely to need during the study
period): immunosuppressanttherapy;chemotherapy;
anticoagulant/antithrombotic therapy (excluding aspirin);
topical glucocorticoids over sensor site only; antibiotic for
chronic infection (e.g. osteomyelitis,endocarditis)
12. Known topical or local anesthetic allergy
13. Known allergy to glucocorticoids
14. Any condition that in the investigator’s opinion would make
the subject unable to complete the study or would make it
not in the subject’s best interest to participate in the study.
Conditions include but are not limited to psychiatric 
conditions, known current or recent alcohol abuse or drug
abuse by subject history, a condition that may increase the
risk of induced hypoglycemia or risk related to repeated
blood testing. Investigator will supply rationale for
exclusion
15. Participation in another clinical investigation (drug 
or device) within 2 weeks prior to screening or
intent to participate during the study period
16. The presence of any other active implanted device (as defined
further in protocol)
Effectiveness Objective:
To determine accuracy of the Eversense® 180 CGM System
measurements through approximately 180 days post-insertion.

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
Investigation
Objectives
Safety Objective:
To demonstrate safety of the Eversense® 180 CGM System 
through 180 days post-Sensor insertion or removal and follow-
up by measuring the incidence of device-related and 
insertion/removal procedure-related serious adverse events 
during the investigation. 
After completion of Visit 8 (day 90 accuracy visit), analysis may 
be performed for the corresponding endpoints and may serve 
as the basis of a regulatory submission. After completion of Visit 
12, analysis will be performed for subsequent visits. There are 
no formal hypothesis tests so there are no type I error concerns.  
Measures/Endpoints
Effectiveness Measures:
The effectiveness measure will be mean absolute relative 
difference (MARD) for paired Sensor and reference measurements 
through 180 days post-insertion for reference glucose values from 
40-400 mg/dL. Effectiveness measures will be evaluated
descriptively.  Neither inferential analysis nor hypothesis testing will 
be performed.
Safety Endpoint:
Incidence of device-related or sensor insertion/removal 
procedure-related serious adverse events through 180 days post-
Sensor insertion or removal and follow-up. 
Other Safety 
Endpoints
1. Incidence of all device-related or sensor insertion/removal 
procedure-related adverse events in the clinic and during home 
use.
2. Incidence of all adverse events in the clinic and during home 
use.
3. Incidence of hospitalizations due to hypoglycemia,
hyperglycemia or ketoacidosis occurring during home
use.
4. Incidence of reported hypoglycemic and hyperglycemic
events occurring during home use.

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
ABBREVIATIONS
AE
Adverse Event
BG
Blood Glucose
BG Meter
Blood Glucose Meter (also known as SMBG Meter)
β-HOB
β-hydroxybutyrate or “ketones,” also abbreviated B-HOB
BMI
Body Mass Index
CD
Compact disc
CFR
Code of Federal Regulations
CGM
Continuous Glucose Monitoring 
CRF
Case Report Form
CRO
Contract Research Organization 
DCF
Data Clarification Form
DKA
Diabetic Ketoacidosis
eCRF
Electronic Case Report Form
EDC
EKG
Electronic Data Capture
Electrocardiogram (also commonly abbreviated as ECG) 
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HbA1c
Hemoglobin A1c or A1C 
HCT
Hematocrit
HIV
Human Immunodeficiency Virus
HHD
Hand Held Device
ICH
International Conference on Harmonization
IRB
Institutional Review Board
ISO
International Organization for Standardization 
MARD
Mean absolute relative difference
MAD
Mean absolute difference
MDI
Multiple Daily Injections
MMA
Mobile Medical Application  
MRD
Mean relative difference
PARD
Percent absolute relative difference
PI
Principal Investigator
POC
Point of Care
SAE
Serious Adverse Event
SMBG
Self-Monitoring Blood Glucose
SQ
Subcutaneous
UADE
Unanticipated Adverse Device Effect 
USB
Universal Serial Bus
YSI
Yellow Springs International (Blood glucose analyzer)

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Protocol #:  CTP-0036   , Version 09  
Effective Date: 14 Apr 2020   
1
INTRODUCTION,IDENTIFICATION OF THE INVESTIGATIONAL DEVICE, AND RATIONALE....... 18
1.1
NAMES, INTENDED USE, AND DESCRIPTION OF STUDY DEVICE ................................... 19
1.2
SUMMARY OF CLINICAL EXPERIENCE .......................................................................... 22
2
STUDY OBJECTIVES............................................................................................................. 22
2.1
EFFECTIVENESS........................................................................................................... 22
2.2
SAFETY........................................................................................................................ 22
3
STUDYDESCRIPTION .......................................................................................................... 22
3.1
STUDY POPULATION: .................................................................................................. 23
3.2
INCLUSION AND EXCLUSION CRITERIA: ....................................................................... 23
3.3
STUDY DESIGN............................................................................................................ 24
4
STUDY METHODS, PROCEDURES AND CLINIC VISITS ........................................................... 27
4.1
VISIT 1 - SCREENING/ENROLLMENT ............................................................................ 30
4.2
DAY 0-VISIT 2- SENSOR INSERTION/TRAINING............................................................. 31
4.3
SENSOR ACCURACY VISITS .......................................................................................... 35
4.4
SENSOR REMOVAL...................................................................................................... 46
4.5
POST-SENSOR REMOVAL FOLLOW UP, VISIT 12 AND VISIT 16 ..................................... 47
5
GENERAL CONSIDERATIONS FOR STUDY VISITS.................................................................. 47
5.1
DEFINITION OF ENROLLMENT..................................................................................... 47
5.2
MEASUREMENT DEVICES– MAINTENANCE/CONTROL TESTING................................... 47
5.3
SENSOR REPLACEMENT .............................................................................................. 48
5.4
PRIMARY SENSOR BLINDING....................................................................................... 48
5.5
SPONSOR PRESENCE AT VISITS.................................................................................... 48
5.6
PHOTOGRAPH/VIDEOGRAPHY .................................................................................... 49
6
CLINICAL LABORATORY EVALUATIONS AND ESTIMATED BLOOD VOLUMES......................... 49
7
SUBJECT SAFETY, STOPPING RULES, AND STUDY EXIT......................................................... 49
7.1
DIABETES AND SAFETY CONSIDERATIONS DURING CLINIC VISITS................................ 49
7.2
MEDICAL OVERSIGHT.................................................................................................. 49
7.3
SENSOR SITE ............................................................................................................... 50
7.4
OTHER CONSIDERATIONS AND SAFETY ASSESSMENTS................................................ 50

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Protocol #:  CTP-0036   , Version 09  
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7.5
HYPOGLYCEMIA.......................................................................................................... 50
7.6
SUBJECT STOPPING RULES .......................................................................................... 54
7.7
STUDY STOPPING RULES ............................................................................................. 56
7.8
TERMINATION OF INVESTIGATOR OR INVESTIGATIONAL SITE..................................... 56
8
RISK AND BENEFIT ANALYSIS .............................................................................................. 56
8.1
POTENTIAL BENEFITS .................................................................................................. 56
8.2
POTENTIAL RISKS ........................................................................................................ 57
8.3
ANTICIPATED ADVERSE EFFECTS ................................................................................. 57
8.4
RESIDUAL RISKS ASSOCIATED WITH THE INVESTIGATIONAL DEVICE............................ 59
8.5
RISKS ASSOCIATED WITH PARTICIPATION IN THE CLINICAL INVESTIGATION................ 59
8.6
POSSIBLE INTERACTIONS WITH CONCOMITANT MEDICAL TREATMENTS .................... 62
8.7
DEXAMETHASONE ...................................................................................................... 62
8.8
ELECTROSTATIC SHOCK............................................................................................... 62
8.9
EFFORTS TO MINIMIZE RISK........................................................................................ 62
8.10
RISK TO BENEFIT RATIO............................................................................................... 63
9
ADVERSE EVENTS ............................................................................................................... 63
9.1
ADVERSE EVENT DEFINITIONS..................................................................................... 64
9.2
MONITORING ADVERSE EVENTS ................................................................................. 65
9.3
ADVERSE EVENT REPORTING ...................................................................................... 66
9.4
DEVICE DEFICIENCIES.................................................................................................. 67
10
SOURCE DOCUMENTATION, CASE REPORT FORMS AND DATA MANAGEMENT................... 67
10.1
SOURCE DOCUMENTS AND CASE REPORT FORMS ...................................................... 67
10.2
GLUCOSE MEASUREMENT DATA FLOW PROCESS........................................................ 68
11
statistical methods............................................................................................................. 69
11.1
STATISTICAL ANALYSIS OVERVIEW .............................................................................. 69
11.2
SAFETY ENDPOINTS .................................................................................................... 72
11.3
EFFECTIVENESS ENDPOINTS........................................................................................ 73
12
DEVICEACCOUNTABILITY................................................................................................... 76
13
ETHICALAND REGULATORY CONSIDERATIONS ................................................................... 76

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Protocol #:  CTP-0036   , Version 09  
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13.1
STATEMENT OF COMPLIANCE AND GOOD CLINICAL PRACTICE ................................... 76
13.2
INFORMED CONSENT AND INVESTIGATIONAL REVIEW BOARD................................... 77
13.3
PAYMENT FOR PARTICIPANTS..................................................................................... 78
13.4
AMENDMENTS TO THE PROTOCOL ............................................................................. 78
13.5
SPONSOR RESPONSIBILITIES ....................................................................................... 78
13.6
INVESTIGATOR REPONSIBILITIES AND DELEGATION OF STUDY SPECIFIC TASKS........... 78
13.7
TRAINING.................................................................................................................... 79
13.8
PROTOCOL COMPLIANCE............................................................................................ 79
13.9
PROTOCOL DEVIATION ............................................................................................... 80
13.10 DOCUMENT STORAGE AND RETENTION...................................................................... 80
13.11 CONFIDENTIALITY OF DATA ........................................................................................ 81
13.12 CLINICAL STUDY MONITORING ................................................................................... 81
13.13 MEDICAL MONITOR.................................................................................................... 81
13.14 AUDITING ................................................................................................................... 82
13.15 INSURANCE AND INDEMNITY...................................................................................... 82
14
FINAL REPORT.................................................................................................................... 82
15
PUBLICATIONPOLICY ......................................................................................................... 83
16
REFERENCES ...................................................................................................................... 84
17
APPENDIX 1 EXAMPLE fIGURES AND TABLES OF STATISTICAL ANALYSIS RESULTS............... 86

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1
INTRODUCTION, IDENTIFICATION OF THE INVESTIGATIONAL DEVICE, AND RATIONALE
In spite of recent improvement in therapies, diabetes mellitus continues to be a difficult
medical condition to treat. The challenge remains to achieve desired glycemic control and
to prevent both the short-term consequences (severe hypoglycemia and DKA) and long-
term complications (retinopathy, neuropathy, nephropathy and cardiovascular problems).
The monitoring of blood glucose by the patient with diabetes is one of the key tools of 
diabetes self-care. The current standard glucose monitoring regimen for patients with
diabetes involves using a small portable meter to obtain a capillary fingertip glucose 
measurement multiple times a day. According to the International Society of Pediatric and 
Adolescent Diabetes (ISPAD), “successful application of intensified diabetes management
with multiple injection therapy or insulin infusion therapy requires frequent self-
monitoring of blood glucose (four to six times a day) and regular, frequent review of the 
results to identify patterns requiring adjustment to the diabetes treatment plan.”1 Despite 
this diagnostic procedure and therapeutic interventions, due to the nature of diabetes
glucose values may fluctuate widely throughout the day. In addition, as the BG meter value
shows only a point in time glucose level, even patients who monitor frequently, may miss
significant hypoglycemic and hyperglycemic excursions. Continuous glucose monitoring 
(CGM), which measures interstitial glucose levels, has been developed recently and has
been shown to be associated with improved glycemic control in adults with type 1
diabetes. Current commercially available CGM devices require the repeated, frequent
insertion of a sensor by the patient.
Senseonics, Inc. a medical device manufacturer headquartered in Germantown, Maryland,
USA, is developing a new CGM System  intended for measuring interstitial fluid glucose
levels in adults with diabetes mellitus. The Eversense® 180 CGM System measures glucose
levels every 5 minutes and is implanted under the skin by a trained health care professional 
(HCP). Unlike commercially available transcutaneous continuous glucose monitoring
devices with short operating lives (up to 14 days), the Eversense® 180 Sensor is intended 
to be inserted subcutaneously with no sensor part protruding from the skin, and the 
operating life is intended to be up to 180 days or until the end of life indicator is reached.
This clinical trial is being carried out to assess the safety and efficacy of the Eversense® 180
CGM System. It is intended that the results of this study will support the targeted indication
as described in Section 1.1 below, providing quantification of accuracy and demonstrate 
safety in clinic and home use settings over the operating life of the Sensor.

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1.1
NAMES, INTENDED USE, AND DESCRIPTION OF STUDY DEVICE
The study investigational Device is the Eversense® 180 CGM System (“System”). The
Eversense® 180 Continuous Glucose Monitoring System is a glucose monitoring device
intended to measure interstitial fluid glucose levels every 5 minutes in individuals with
diabetes for the operating life of the sensor. The Eversense® 180 Continuous Glucose
Monitoring System is intended to be used:
!
To provide real-time glucose readings directly to the user
!
To provide glucose trend information
!
To provide alerts for the detection and prediction of episodes of low
blood glucose (hypoglycemia) and high blood glucose 
(hyperglycemia).
The Eversense® 180 CGM System consists of:
1. Glucose Sensor, (approximately 3.5 mm [0.138”] diameter x 18.3 mm [0.720”] length) 
which has a ring that elutes the steroid dexamethasone, primary and secondary (in 
subjects with 2 sensors) 
2. Battery-powered external Transmitters (“Transmitter”, primary and secondary (in 
subjects with 2 sensors)
3. Mobile Medical Application (MMA) for display of glucose information that runs on
a Handheld Device (HHD).    

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Accessories to the system include:
1.
Adhesive Patch: To secure the Transmitter over the Sensor
2.
Insertion tool (Blunt dissector, Sensor Inserter): To place the Sensor into the 
subcutaneous space.
3.
Charger and Charging Cradle: To charge the Transmitter.
The use of the Eversense® 180 system in this clinical study is outside the current 
commercial indications for use.
1.1.1
DESCRIPTION
The Sensor uses a selective, fully reversible binding between glucose and a unique
fluorescent indicator macromolecule that is grafted on the surface of the Sensor. The
fundamental recognition reaction is a reversible condensation of the cis-diol groups of 
glucose with the bis-boronate moiety of an indicator. Glucose binding by the indicator
macromolecule results in an increase in fluorescence intensity. Glucose signal
transduction is accomplished by measuring the fluorescence intensity modulation using
the Sensor’s optical system.
The System Transmitter powers the Sensor and receives signals from the Sensor across
the skin. The Sensor does not contain a battery or other stored power source; instead

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it is powered discretely, as needed, by a simple inductive magnetic link between the
Transmitter and Sensor. Signals carrying glucose concentration data are superimposed
upon the magnetic power link between the two components. This results in “passive”
telemetry, rather than an “active” radio frequency (RF) transmission, between the 
Sensor and Transmitter. Between readings, the Sensor remains electrically dormant
and fully powered down. At each query (automatically set for approximately every five 
minutes, with a duration of approximately 100 milliseconds), the Transmitter sends
power (via magnetic link) to activate the sensor, and then uses this same magnetic link
to capture the reading. Finally, the Transmitter calculates and stores the measured
glucose value for transmission to the Mobile Medical Application.
Components of the Eversense® 180 CGM System are traced by serial number and/or lot
number. The Sensor, Sensor holder, insertion tool, and blunt dissector are provided
sterile. Sterilized components also have an expiration date. The device is labeled in
compliance with regulatory language requirements identifying it as investigational. The
Instructions for Use are provided with each shipment.
Insertion of the Sensor is a minimally invasive procedure and clinical investigators 
representing the intended use population (Endocrinologists, Internists, General and 
Family Practitioners and their medical staff) will be appropriately trained in the
procedure prior to insertion or removal of the Sensor. Training and qualifications of 
investigators will be documented.
Transmitters will be provided for single-subject use in this clinical trial.
1.1.2
CALIBRATION
The primary Eversense® 180 CGM System will be calibrated by the Subjects according to
the Eversense® 180 CGM User Guide, using the study-provided, commercially available
BG Meter (Subject SMBG Meter), according to the SMBG meter manufacturer
instructions. The calibration process automatically moves through three phases: Warm
Up, Initialization, and Daily Calibration:
!
Warm Up is the first 24 hours after Sensor insertion. During this period, Glucose 
information is not calculated. No calibration is performed.
!
Initialization can be performed a minimum of 24 hours after Sensor insertion.
Following the WarmUp phase, the entering of four successful calibration BG readings
within 24 hours is required for successful completion of Initialization. Glucose 
information will begin to be calculated after the second calibration is entered
successfully.

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!
Daily Calibration requires a minimum of 2 calibration per day.
The secondary Eversense® 180 CGM System will not require calibration and will have the 
ability to collect and log raw data only, and it will not calculate or store glucose 
information.
1.2
SUMMARY OF CLINICAL EXPERIENCE
Three major pivotal safety and efficacy studies have been completed and submitted for 
regulatory approval. The European pivotal study, PRECISE was completed in August 2015 
and Senseonics received CE Mark in May 2016; two U.S. pivotal studies (PRECISE II, 
completed in July 2016 and PRECISION, completed in February 2018) were also completed 
and FDA approval was received in June 2018. These studies demonstrated that the 
Eversense® 180 CGM System provided reliable glucose readings for periods of up to 
approximately 180 days when compared to laboratory blood glucose analyzer 
measurements, with no notable safety issues. 
2
STUDY OBJECTIVES
2.1
EFFECTIVENESS
The effectiveness objective is to determine accuracy of the Eversense® 180 CGM System
measurements through approximately 180 days post-insertion. The exploratory 
objectives are to determine other relevant Eversense® 180 CGM System performance 
measures during the period of Sensor use and are detailed further in Section 11.3.
2.2
SAFETY
The safety objective is to demonstrate safety of the Eversense® 180 CGM System 
through 180 days post-insertion by measuring the incidence of device-related or sensor 
insertion/removal procedure-related serious adverse events (SAEs) during the 
investigation.
After completion of Visit 8 (day 90 accuracy visit), analysis may be performed for the 
corresponding endpoints and may serve as the basis of a regulatory submission. After 
completion of Visit 12, analysis will be performed for subsequent visits. There are no 
formal hypothesis tests so there are no type I error concerns.
3
STUDYDESCRIPTION

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3.1
STUDY POPULATION:
The study population includes adults with diabetes mellitus.
3.2
INCLUSION AND EXCLUSION CRITERIA:
3.2.1
INCLUSION CRITERIA
Male and Female Subjects meeting all of the following inclusion criteria will be included
in this study:
1.
Adult subjects, age ≥18 years
2.
Clinically confirmed diagnosis of diabetes mellitus for ≥1 year.
3.
Subject has signed an informed consent form and is willing to comply with protocol
requirements
3.2.2
EXCLUSION CRITERIA
Subjects meeting any of the following exclusion criteria at the time of screening will be 
excluded from this study:
1.
History of unexplained severe hypoglycemia in the previous 6 months. Severe
hypoglycemia is defined as hypoglycemia resulting in loss of consciousness or
seizure
2.
History of diabetic ketoacidosis requiring emergency room visit or hospitalization in
the previous 6 months
3.
Subjects with gastroparesis
4.
Female subjects of childbearing capacity (defined as not surgically sterile or not
menopausal for ≥1 year) who are lactating or pregnant, intending to become
pregnant, or not practicing birth control during the course of the study
5.
A condition preventing or complicating the placement, operation or removal of the 
Sensor or wearing of transmitter, including upper extremity deformities or skin 
condition
6.
Symptomatic coronary artery disease; unstable angina; myocardial infarction,
transient ischemic attack or stroke within 6 months; uncontrolled hypertension
(systolic>160 mm HG or diastolic >100 mm Hg at time of screening); current
congestive heart failure; history of cardiac arrhythmia (benign PACs and PVCs 
allowed). Subjects with asymptomatic coronary artery disease (e.g. CABG, stent 
placement or angioplasty) may participate if negative stress test within 1 year prior 
to screening and written clearance from Cardiologist documented.
7.
Hematocrit <30% or >60%

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8.
History of hepatitis B, hepatitis C, or HIV
9.
Current treatment for a seizure disorder unless written clearance by neurologist to
participate in study
10. History of adrenal insufficiency
11. Currently receiving (or likely to need during the study period): immunosuppressant
therapy; chemotherapy; anticoagulant/antithrombotic therapy (excluding aspirin);
topical glucocorticoids over sensor site only; antibiotics for chronic infection (e.g.
osteomyelitis, endocarditis)
12. Known topical or local anesthetic allergy
13. Known allergy to glucocorticoids
14. Any condition that in the investigator’s opinion would make the subject unable to 
complete the study or would make it not in the subject’s best interest to
participate in the study. Conditions include, but are not limited to, psychiatric
conditions, known current or recent alcohol abuse or drug abuse by subject
history, a condition that may increase the risk of induced hypoglycemia or risk
related to repeated blood testing. Investigator will supply rationale for exclusion
15. Participation in another clinical investigation (drug or device) within 2 weeks 
prior to screening or intent to participate during the study period
16. The presence of any other active implanted device*
* An example of an active implanted device includes but is not limited to an implantable
defibrillator. Passive implantable devices are allowed. An example of a passive
implantable device includes, but is not limited to, a cardiac stent.  
3.3
STUDY DESIGN
3.3.1
OVERVIEW
This is a prospective, multi-center study, whereby approximately 210 subjects will be 
enrolled, and 180 subjects will be inserted in the United States at up to 15 sites. The
investigation will include both clinic visits and home use of the Eversense® 180 CGM 
System. A minimum of 80 subjects, will have two Sensors inserted by trained 
Investigators. The Sensor(s) will be inserted in the upper arms of the subjects. The
accuracy of the Eversense® 180 CGM System will be evaluated during clinic visits 
comparing Sensor glucose values and plasma glucose values measured on a bedside 
glucose analyzer. For qualifying subjects, during the clinic visits, there will be planned
hyperglycemia and hypoglycemia challenges, as described in Section 4.3.

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In this study, including the clinic and home settings, all diabetes care decisions will be 
based on SMBG blood glucose values and clinical standard of care, rather than 
Eversense® 180 CGM System results.
To ensure adequate numbers of subjects for specific scenarios of interest, there will be 
two randomizations:
!
Shift of the Day 1 sensor accuracy assessment: early (hours 1-8) vs. middle (hours 
9-16) vs. late (hours 17-24)
!
Day of the Visit 4 accuracy assessment: Day 7 vs. Day 14
Shift of the Day 1 assessment will be for the Day 1 of sensor life (the day after insertion). 
Both randomizations are independent of one another.
The Subject visit schedule includes 12 visits over a period of approximately 8 months 
(inclusive of visit windows from screening visit through follow-up visit). For the subset of 
subjects inserted with 2 sensors, the subject visit schedule includes 16 visits over a period 
of proximately 14 months. 
The study is anticipated to take approximately 26 months, including the enrollment
period.
3.3.2
JUSTIFICATION FOR CLINICAL INVESTIGATIONAL DESIGN
The design of the clinical investigation was developed following a review of current
published clinical studies evaluating the accuracy of continuous glucose monitors.2, 3, 4   In
addition, the recommendations of the following standards and guidelines were 
considered in the clinical investigation design:
!
CLSI: Performance Metrics for Continuous Interstitial Glucose Monitoring:
Approved Guideline. CLSI Document POCT05-A. Wayne, PA. Clinical and
Laboratory Standards Institute. 2008.5
!
ISO: In-vitro Diagnostic Test Systems-Requirements for Blood Glucose Monitoring
Systems for
Self-Testing in Managing Diabetes Mellitus. ISO 15197. Geneva.
International Organization for Standardization. 2013.6
!
FDA: Content of Premarket Submissions for Management of Cybersecurity in
Medical Devices. Guidance. 2014.7

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!
FDA: The Content of Investigational Device Exemption (IDE) and Premarket
Approval (PMA) Applications for Artificial Pancreas Device Systems. Guidance.
2012.8
!
FDA: Design Considerations for Pivotal Clinical Investigations for Medical Devices.
Guidance 2013.9
The operational components of the investigation are consistent with:
!
US Code of Federal Regulations (21 CFR Part 812)
!
ICH GCP E6
Potential for bias during this investigation has been minimized by design of a well-
controlled study, expected conduct under the terms of an approved study protocol, use 
of specific inclusion and exclusion criteria, careful definitions for study procedures and 
outcomes and prospectively defined methods of data analysis and careful selection of 
investigators and investigative sites.
3.3.3
OVERVIEW OF VISIT SCHEDULE
!
Screening Visit (Visit 1): Following the informed consent process, the screening
evaluation will determine subject eligibility for sensor insertion. This visit will last
approximately 2 hours. Screening will include medical and diabetes history, physical 
examination, quality of life questionnaire and laboratory assessments including EKG.  
Randomization as described above will occur at this visit.
!
Day 0 (+0-45 days) Sensor Insertion (Visit 2):   Sensors are inserted by Investigator
in the upper arm(s). A minimum of 80 subjects, will have two Sensors inserted.
Subject training on study and devices. Visit lasting approximately 2 to 3 hours.
!
Sensor Accuracy Visits: The following visits include Sensor accuracy assessment
with bedside reference comparison, Sensor calibration with Subject SMBG
Meter, and safety assessments.   Procedure details are described in Section 4 of 
the protocol.
o
Day 1 – Hours 1-8 (±0 Days) Visit 3A. Visit lasting approximately 11 hours. (Day 
1 Early Shift)
o
Day 1 – Hours 9-16 (±0 Days) Visit 3B. Visit lasting approximately 10 hours.
(Day 1 Middle Shift)
o
Day 1 – Hours 17-24 (±0 Days) Visit 3C. Visit lasting approximately 10 hours.
(Day 1 Late Shift)
o
Day 7 (± 1 Day) Visit 4A.  Visit lasts approximately 10 hours. (Day 7 Group)
o
Day 14 (± 1 Day) Visit 4B.  Visit lasts approximately 10 hours. (Day 14 Group)
o
Day 22 (± 1 Day) Visit 5.  Visit lasts approximately 10 hours. (all subjects)

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o
Day 30 (-3/+7 Days) Visit 6. Visit lasting approximately 10 hours (all subjects). 
o
Day 60 (-7/+7 Days) Visit 7. Visit lasting approximately 10 hours (all subjects). 
o
Day 90 (-7/+7 Days) Visit 8. Visit lasting approximately 10 hours (all subjects). 
o
Day 120 (-7/+7 Days) Visit 9. Visit lasting approximately 10 hours (all subjects). 
o
Day 150 (-7/+7 Days) Visit 10. Visit lasting approximately 10 hours (all 
subjects). 
o
Day 180 (-3/+2 Days) Visit 11. Visit lasting approximately 12 hours (all 
subjects). 
 Following the Day 180 accuracy visit, Sensors are removed at end of visit 
or within 7 days of the day 180 accuracy visit. For subjects with 2 sensors, 
only the primary sensor will be removed and a new sensor will be 
inserted. The Secondary sensor will remain in situ. Subjects will complete 
the following additional visits.
!
Clinic Visits: Subjects with 2 sensors will return to the clinic approximately every 60 
days (±7 days) after completion of the first 180 day phase of the study. The subject’s
transmitters and study meter will be downloaded. Study staff will review fingerstick 
and study compliance with the subject. Study staff will assess for any new or ongoing 
Adverse Events.  
o
Day 240 (±7 Days) Visit 13. Visit lasting approximately 1 hours (2 sensor 
subjects).
o
Day 300 (-±7 Days) Visit 14. Visit lasting approximately 1 hours (2 sensor 
subjects).)
o
Day 365 (+7 Days) Visit 15. Visit lasting approximately 1 hours (2 sensor 
subjects).
!
Follow-up Visits (Visit 12 & 16): Sensor Site Assessment is performed approximately
10 days (- 3/ +7 days) after Sensor removals and insertion, as applicable, to assess
Sensor sites. At this visit, if there is a concern by investigator about healing of sensor
site, subject will return in approximately 10 days and followed until resolution.
4
STUDY METHODS, PROCEDURES AND CLINICVISITS
Each visit is described in detail in this section.

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Day Post-Insertion
-45 -0
0
1
7
14
22
30
60
90
120
150
180
10 Day 
Follow-
up
240
300
365
10 Day 
Follow-
up
Visit Type
Screening
Sensor 
Insertion 
& 
Training
Accuracy 
Visit. 
Accuracy 
Visit (Day 
7)
Accuracy 
Visit (Day 
14)
Accuracy 
Visit
Accuracy 
Visit
Accuracy 
Visit
Accuracy
Visit
Accuracy
Visit
Accuracy 
Visit 
Accuracy
Visit & Sensor 
Removal
Follow-
up
Clinic 
Visit
Clinic 
Visit
Clinic 
Visit & 
Sensor 
Removal
Follow-
up
Study Visit and 
Window
Visit 1
Visit 2
(+0 to 45 
days after 
Visit 1)
Visit 3A, 
3B, 3C 
(± 0 
Days)
Visit 4A
(± 1 Day)
Visit 4B
(± 1 Day)
Visit 5
(± 1 Day)
Visit 6
(-3/+7 
Days)
Visit 7
(±7 Days)
Visit 8
(±7 
Days)
Visit 9
(±7 
Days)
Visit 10
(±7 
Days)
Visit 11
(-3/+2 Days)
Visit 12
(-3/+7
days)
Visit 13
(±7 
Days)
Visit 14
(±7 
Days)
Visit 15
(+7 Days)
Visit 16
(-3/+7
days)
Anticipated Length 
of Visit 
2 Hours
2-3 
Hours
10-11
hours
10 hours
10 hours
10 hours
10 hours
10 hours
10 hours
10 hours
10 hours
12 hours
1 Hour
1 Hour
1 hour
1 hour
1 Hour
ICF Process
X
Screening history, 
exam, labs to assess 
I&E
X
Sensor Insertion
X
X
Device Training
X
Urine pregnancy
X
X
X
X
X
X
X
X
X
X
X
X
IV Catheter
X
X
X
X
X
X
X
X
X
X
Approximate length 
of time to collect 
blood Samples
8 Hours
8 Hours
8 Hours
8 Hours
8 Hours
8 Hours
8 Hours
8 Hours
8 Hours
10 Hours
HCT
X
X
X
X
X
X
X
X
X
X
X
A1C (2.0 mL)
X
X
X
X
Fingerstick blood 
glucose and ketones 
per protocol
X
X
X
X
X
X
X
X
X
X
X
Download 
Transmitter and BG 
Meters
X
X
X
X
X
X
X
X
X
X
X
X
X
Assess changes in 
medications and 
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assess Sensor site
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hypoglycemia 
Hyperglycemia 
Challenge1
X
X
X
X
X
X
X
X
X
X
Questionnaires2
X
X
X
X

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1 Only hypoglycemiachallenge or hyperglycemia challenge, depending on glucose level Investigator discretion and patient safety will also be considered in determining appropriate challenge. 
2 Diabetes Distress Scale at screening, day 90 and day 180/removal and day 365(visits 1, 8, 11, and 15); CGM satisfaction scale at day 180/removal and day 365/removal (visit 11 and Visit 15). 
Questionnaires may also be given at the time the subject’s primary sensor is confirmed to enter clinical mode.
Sensor Removal
X
X
Approximate 
Samples for glucose 
analysis
43
43
43
43
43
43
43
43
43
51
Estimated Blood 
Draw Volume
2
86
86
86
86
86
86
88
86
86
104

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4.1
VISIT 1 - SCREENING/ENROLLMENT
Subjects will be enrolled into the study following informed consent. Screening evaluation 
will determine subject eligibility for sensor insertion. No study-specific procedures may be 
performed prior to informed consent signature. The Screening Visit is anticipated to last 
approximately 2 hours. The visit will occur within 45 days before the Sensor Insertion Visit 
(V2). In the event that an insertion visit cannot be scheduled within the 45 day window, a 
qualified subject may repeat the screening visit.
The Screening Visit includes performing/collecting the following information: 
•
Demographics - including age, gender at birth, race/ethnicity, dominant hand, and BMI
•
Diabetes History - including type of diabetes, date of diagnosis or length of diabetes, 
history of DKA and severe hypoglycemia, current treatment (type of insulin and type of 
insulin delivery (injections or insulin pump), insulin doses, and when applicable: basal 
rates, correction factors, glucose targets, insulin duration, insulin to carbohydrate 
ratios).
•
Current and Past Medical History - including concomitant medications
•
Physical examination and vital signs - including height, weight, blood pressure, pulse, 
temperature, assessment of potential sensor insertion sites, assessment of venous 
access for repeated blood draws
•
EKG - An EKG will be performed with the results kept in the subject records  
•
Laboratory - Blood samples (approximately 2 ml total) will be drawn for hemoglobin 
A1c (HbA1c)
!
Quality of Life questionnaire - The diabetes distress scale will be administered
4.1.1
POINT OF CARE TESTING
!
Urine pregnancy test- for females of childbearing capacity (defined as not surgically 
sterile or not menopausal for ≥ 1 year)
!
Hematocrit (using local lab or point of care testing device)
4.1.2
RANDOMIZATION
To ensure adequate numbers of subjects for specific scenarios of interest, there will be 
two randomizations:

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•
Shift of the Day 1 sensor accuracy assessment: early (hours 1-8) vs. middle (hours 9-
16) vs. late (hours 17-24)
•
Day of the Visit 4 accuracy assessment: Day 7 vs. Day 14
Both randomizations are independent of one another.
4.2
DAY 0-VISIT 2- SENSOR INSERTION/TRAINING
4.2.1
SUBJECT ADMISSION
The subject will arrive at the clinic, at an appropriate time to allow for sensor insertion to 
occur a minimum of 24 hours before any planned study activities, and the following tests 
will be performed to confirm eligibility:
•
Female subjects of childbearing capacity will undergo a urine pregnancy test. If 
positive, the subject will discontinue study participation. Subject withdrawal will be 
documented.
•
Fingerstick glucose and ketones will be measured.
•
The study team will confirm the absence of a febrile or vomiting illness within 24 
hours of the admission.
•
If all admission criteria are not met, the subject will be rescheduled. If all of the 
admission readiness conditions are met, the subject will be admitted to the Clinical 
Research Unit. 
The subject will be asked about any adverse events or changes to medications since 
the last study visit.
4.2.2
DEVICE PREPARATION
All Study devices will be time synchronized and checked for function as described in 
section 4.3.1.3.
4.2.3
SENSOR INSERTIONS
Each subject will have the Sensor(s) inserted at Visit 2 (Day 0); above the elbow of their 
arms. The study team will prepare the Sensor insertion site appropriately. The hair at the 
insertion area may be clipped in order to ensure appropriate visualization of the insertion 
site. The Sensor will be prepared by qualified personnel (Sponsor personnel or trained 
investigative staff).

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A trained study clinician will insert the Sensor(s) into the subcutaneous tissue using 
appropriate technique described in the Eversense® 180 CGM Sensor Insertion and 
Removal Instructions. The location of the sensor(s) will be documented.  
Subjects will be advised that they may take over the counter pain medication if needed 
for any discomfort after the insertion process. No medication, including medication-
containing creams and patches is to be applied over the Sensor insertion sites.
Subjects will be advised on the proper incision care:
! Do not swim or soak in a tub for five days 
! Avoid strenuous activities that may pull at the incision or cause a lot of sweating 
around the insertion area while the incision heals 
! Replace Tegaderm™ if it becomes saturated; otherwise, leave it on over the Steri-
Strips™ for at least 2 days
! Leave Steri-Strips™ on until they fall off 
! Trim the edges of the Steri-Strips™ if they start to curl; do not remove them when 
doing so 
! Place the smart transmitter over the Tegaderm™ after the first day 
Subjects will be advised to notify the study doctor if:
! Steri-Strips™ come off before incision is fully closed 
! They develop a fever, or experience pain, redness, swelling, warmth or drainage at 
the incision site 
! They experience a significant change in health or well-being that they believe is 
related to the incision site
A minimum of 80 subjects will have two sensors inserted, one in each upper arm.
Identification of the Sensor(s), Transmitter(s) and accessories will be recorded (part 
number, serial number, lot number, and expiration date as applicable).
After Sensor insertion, the transmitter(s) will be worn briefly (approximately 20 minutes) 
while the sensor is linked to the transmitter, and to ensure proper operation of the 
system (confirmation of system operation).  
4.2.4
DEVICE DISBURSEMENT
Subjects will be assigned the following devices:
!
Eversense® 180 Continuous Glucose Monitoring (CGM) Systems consisting of the 
following:
o
One Transmitter and accessories (charger, adhesive patches)  

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o
Handheld Device (1 per Subject) running the Mobile Medical Application (MMA)
o
Eversense® 180 CGM User Guides
!
A widely-used, commercially available FDA-approved self-monitoring blood glucose 
(SMBG) meter and associated supplies:
o
BG meter strips
o
Lancets
o
control solution
o
Instructions for Use
For those subjects with two sensors inserted, a second transmitter will be provided. See 
Section 4.2.10 for a description of the operation requirements of two separate CGM 
systems.
4.2.5
SUBJECT TRAINING
Subjects will be issued transmitters as appropriate and trained in their use along with a 
hand-held device which will be used for entering calibration information.
The subject will be given instructions on how to contact study staff for 24 hours per day 
to report any study- related problems.  The subject will be instructed to contact the study 
staff for prolonged hyperglycemia, severe hypoglycemia, or if he/she experiences nausea, 
vomiting, or abdominal pain within 48 hours after discharge. The subject will be 
instructed to contact the study staff for any problems related to the sensor sites, 
including fever, pain, redness, itching, discharge, warmth or swelling at the sensor 
insertion sites. If infection is experienced, standard medical practice and administration of 
antibiotics as required should be followed until resolution. Subjects will be further 
instructed to advise the investigator if new medications have been prescribed or started, 
or if any hospitalizations or significant medical changes have occurred.
The subject will be instructed on the proper use and quality control of the Subject SMBG 
Meter including the number and timing of fingersticks expected during each day
(approximately 7 times per day (before meals, approximately 2 hours after meals, and at 
bedtime)). Subjects will be requested to enter all SMBG readings into the Eversense® app 
as glucose events. Subjects will be monitored for compliance to a minimum of 4 SMBG 
readings per day including at least 1 pre-prandial and 1 before bedtime, and will be 
contacted by the study site if they are found to be out of compliance. Subjects will be 
requested to enter all insulin injections/boluses into the Eversense app to aid in 
evaluation of subject compliance with adjunctive use of the CGM system.

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The subject will be instructed on the proper use of the Transmitter and Mobile Medical 
Application (refer to the Eversense® 180 CGM User Guides). The transmitter(s) will be 
worn over the sensor at all times (except while charging) starting approximately 24 hours 
post insertion. Subjects will be prompted to calibrate the sensor using fingerstick 
measurements using the Subject SMBG meter.  
4.2.6
DISCHARGE
Discharge will occur upon completion of confirmation of system operation and subject 
training. The site will document any adverse events that may have occurred during the 
visit.
4.2.7
ESTIMATED VISIT DURATION
The total duration of the inpatient visit is approximately 2-3 hours
4.2.8
SUBJECTS ASSIGNED TO Day 1 Early Shift Group
Subjects in Day 1 Early Shift Group will leave their transmitters at the clinical site and will 
return the following day for visit 3A sensor accuracy visit. They will place the transmitters 
and perform their first calibrations at the clinical site as prompted by the Eversense® 180 
CGM System.
4.2.9
SUBJECTS ASSIGNED TO Day 1 Middle and Late Shift Groups
Subjects in Day 1 Middle and Late Shift Groups will be instructed to start wearing the 
transmitters approximately 24 hours after the sensor was inserted.  Subjects will then be 
prompted by the Eversense® 180 CGM System to enter their first calibration, and the 
Eversense® 180 system will enter the initialization phase. The clinical site should 
communicate with the subject during this time to make sure the subject was successful 
with entering initialization.
4.2.10 SUBJECTS WITH TWO SENSORS INSERTED
Subjects with two sensors inserted will be issued two transmitters to be worn over the 
sensors. Transmitters will be designated as primary (left arm) and secondary (right arm) 
and will have distinguishing visual marks to ensure matching to the correct limb. Each 
transmitter is linked to a specific sensor as described in the Eversense® 180 CGM system
User Guide. Subjects will be issued a hand-held display which will be used for entering 
calibration information into the primary transmitter only. The secondary transmitter 
worn on the opposite arm will have the ability to collect and log data only and will not 
calculate and store glucose. The handheld device, when paired to the secondary 
transmitter, will only display battery level and the placement guide used for wearing the 
transmitter as described in the Eversense® 180 CGM system User Guide.

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The secondary transmitter will use the SMBG calibration points collected and entered 
into the primary system (using the same time stamp information) for calculation of 
glucose results in the analysis data set.
This subset of subjects will be used to explore the following endpoints: PARD, and 
dominant vs non-dominant arm effects. Analysis of data from subjects with two sensors 
inserted is further described in Section 11. Additionally, this subset of subjects will 
continue participation for 365 days of sensor wear. At Day 180, the primary sensor will be 
removed and a new sensor will be inserted. The secondary sensor will remain in situ for 
observation of sensor life for up to 365 days.
4.3
SENSOR ACCURACY VISITS
Day 1 (Day 1 Early Shift Group only) – Visits 3A
Approximate visit duration - 11 hours
Approximate sampling duration – 8 hours
Approximate visit timeline:
Approximate 
time*
Activity**
Time relative to first IV 
sample
~06:00
Admission
T=0 -2:00
~07:15-07:45
Free range glucose control
T=0 -0:45 - -0:15
~08:00
First IV blood sample drawn 
T=0 0:00
~08:00 –
13:00
For qualifying subjects, hypoglycemia 
challenge to achieve hypoglycemia target 
<70 mg/dL for 1 hour
! Sampling every 5 min when glucose 
≤70 mg/dL 
! Challenge may be stopped once 13 YSI 
values ≤70 mg/dL are collected
! Subjects fed at end of challenge
! Note: Subjects should not be held <55 
mg/dL for more than 20 minutes
T=0 0:00 – +5:00

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Approximate 
time*
Activity**
Time relative to first IV 
sample
~08:00 –
13:00
Alternatively, for qualifying subjects, 
hyperglycemia challenge to achieve 
hyperglycemia target >300 mg/dL for 75 
minutes
! Sampling every 5 min when glucose 
≥300 mg/dL 
! Challenge may be stopped once 16 YSI 
values ≥300 mg/dL are collected 
T=0 0:00 – +5:00
~08:00 –
13:00
For those subjects not following a 
basal/bolus routine on MDI or CSII, glucose 
control will be free range
T=0 0:00 – +5:00
~09:00
Fingerstick blood glucose
T=0 +1:00 
~10:00
Fingerstick blood glucose
T=0 +2:00 
~11:00
Fingerstick blood glucose
T=0 +3:00 
~12:00
Fingerstick blood glucose
T=0 +4:00 
~13:00
Fingerstick blood glucose
T=0 +5:00 
~13:00-16:00
Recovery Period with meal/bolus and 
glucose stabilization
T=0 +5:00 - +8:00
~14:00
Fingerstick blood glucose
T=0 +6:00 
~15:00
Fingerstick blood glucose
T=0 +7:00 
~16:00
Fingerstick blood glucose
T=0 +8:00 
~ 15:00 –
16:00
Discharge preparation period
~16:00
Last IV blood sample draw
T=0 +8:00
~16:30
Discharge
T=0 +8:30
  *Times may change based on time sensors are inserted.
** CGM calibration will be performed as prompted by the Eversense® 180 CGM System
throughout the visit.
Other 8-Hour Sampling Sensor Accuracy Visits – Visits 3B (Day 1 Middle Shift Group), 3C
(Day 1 Late shift Group) and Visits 4-10 (all subjects)
Approximate visit duration - 10 hours
Approximate sampling duration – 8 hours
Approximate 
time*
Activity**
Time relative to first IV 
sample
~07:30
Admission
T=0 -:30
~07:30-07:45
Free range glucose control
T=0 -0:45 - -0:15
~08:00
First IV blood sample drawn.
T=0 0:00

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Approximate 
time*
Activity**
Time relative to first IV 
sample
~08:00 –
13:00
For qualifying subjects, hypoglycemia 
challenge to achieve hypoglycemia target 
<70 mg/dL for 1 hour
! Sampling every 5 min when glucose 
≤70 mg/dL 
! Challenge may be stopped once 13 YSI 
values ≤70 mg/dL are collected
! Subjects fed at end of challenge
! Note: Subjects should not be held <55 
mg/dL for more than 20 minutes
T=0 0:00 – +5:00
~08:00 –
13:00
Alternatively, for qualifying subjects, 
hyperglycemia challenge to achieve 
hyperglycemia target >300 mg/dL for 75 
minutes
! Sampling every 5 min when glucose 
≥300 mg/dL 
! Challenge may be stopped once 16 YSI 
values ≥300 mg/dL are collected 
T=0 0:00 – +5:00
~08:00 –
13:00
For those subjects not following a 
basal/bolus routine on MDI or CSII, glucose 
control will be free range
T=0 0:00 – +5:00
~09:00
Fingerstick blood glucose
T=0 +1:00 
~10:00
Fingerstick blood glucose
T=0 +2:00 
~11:00
Fingerstick blood glucose
T=0 +3:00 
~12:00
Fingerstick blood glucose
T=0 +4:00 
~13:00
Fingerstick blood glucose
T=0 +5:00 
~13:00-16:00
Recovery Period with meal/bolus and 
glucose stabilization
T=0 +5:00 - +8:00
~14:00
Fingerstick blood glucose
T=0 +6:00 
~15:00
Fingerstick blood glucose
T=0 +7:00 
~16:00
Fingerstick blood glucose
T=0 +8:00 
~ 15:00 –
16:00
Discharge preparation period
~16:00
Last IV blood sample draw
T=0 +8:00
~16:30
Discharge
T=0 +8:30
        *Times may change based on time sensors are inserted.
** CGM calibration will be performed as prompted by the Eversense® 180 CGM System
throughout the visit.

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10-Hour Sampling Sensor Accuracy Visit –Visit 11 (all subjects)
Approximate visit duration - 12 hours
Approximate sampling duration – 10 hours
Approximate 
time
Activity**
Time relative to first IV 
sample
~07:30
Admission
T=0 -:30
~07:30-07:45
Free range glucose control
T=0 -0:45 - -0:15
~08:00
First IV blood sample drawn
T=0 0:00
~08:00 –
13:00
For qualifying subjects, hypoglycemia 
challenge to achieve hypoglycemia target 
<70 mg/dL for 1 hour
! Sampling every 5 min when glucose 
≤70 mg/dL 
! Challenge may be stopped once 13 YSI 
values ≤70 mg/dL are collected
! Subjects fed at end of challenge
! Note: Subjects should not be held <55 
mg/dL for more than 20 minutes
T=0 0:00 – +5:00
~08:00 –
13:00
Alternatively, for qualifying subjects, 
hyperglycemia challenge to achieve 
hyperglycemia target >300 mg/dL for 75 
minutes
! Sampling every 5 min when glucose 
≥300 mg/dL 
! Challenge may be stopped once 16 YSI 
values ≥300 mg/dL are collected 
T=0 0:00 – +5:00
~08:00 –
13:00
For those subjects not following a 
basal/bolus routine on MDI or CSII, glucose 
control will be free range
T=0 0:00 – +5:00
~09:00
Fingerstick blood glucose
T=0 +1:00 
~10:00
Fingerstick blood glucose
T=0 +2:00 
~11:00
Fingerstick blood glucose
T=0 +3:00 
~12:00
Fingerstick blood glucose
T=0 +4:00 
~13:00
Fingerstick blood glucose
T=0 +5:00 
~13:00-18:00
Recovery Period with meal/bolus and 
glucose stabilization
T=0 +5:00 - +8:00
~14:00
Fingerstick blood glucose
T=0 +6:00 
~15:00
Fingerstick blood glucose
T=0 +7:00 
~16:00
Fingerstick blood glucose
T=0 +8:00 
~17:00
Fingerstick blood glucose
T=0 +9:00 

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Approximate 
time
Activity**
Time relative to first IV 
sample
~18:00
Fingerstick blood glucose
T=0 +10:00 
~ 17:00 –
18:00
Discharge preparation period
~18:00
Last IV blood sample draw
T=0 +10:00
~18:30
Discharge
T=0 +10:30
        ** CGM calibration will be performed as prompted by the Eversense® 180 CGM System
throughout the visit.
4.3.1
THE FOLLOWING PROCEDURES/INSTRUCTIONS WILL BE FOLLOWED FOR ALL ACCURACY 
VISITS
4.3.1.1
PRE-VISIT PHONE CALL (DAY 7-180 VISITS)
Approximately 12 hours prior to the Accuracy Visit, site personnel will contact the subject 
to ensure the subject is in compliance with study device wear prior to the scheduled start 
of glucose sampling.   Subjects may be instructed to calibrate at a specific number of 
hours before the scheduled visit start in order to assess accuracy over the entire 
calibration window. Subjects may also be given appropriate instructions regarding pre-
visit medications and meals.
4.3.1.2
SUBJECT INSTRUCTIONS PRIOR TO ADMISSION
Prior to admission, subjects should take morning medications as usual as follows:
!
If challenge subjects need to eat or take insulin for safety reasons, they should inform 
study staff of this information on arrival to the clinic.
!
Subjects should consume the food they would normally consume to treat or prevent 
hypoglycemia at the blood glucose level they feel is appropriate.
A clinician trained in the treatment of diabetes should also discuss and make 
recommendations about each subject’s insulin regimen for the remainder of the day to 
prevent post-visit rebound hypoglycemia which can occur 12 hours later.
4.3.1.3
DEVICE SET UP
4.3.1.3.1 DEVICE CALIBRATION
Prior to subject blood sampling, the CRC study equipment (YSI glucose analyzer, ketone 
meter and study-supplied Subject SMBG Meter) will be checked for proper function and 
the appropriate quality controls will be run per the manufacturer’s guidelines as 
appropriate. 

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4.3.1.3.2 TIME SYNC
At each study visit the date and time on all study devices (i.e.  study clocks, laptop(s), 
Subject SMBG Meter, Reference instrument and Eversense® 180 Continuous Glucose 
Monitoring System) will be synchronized at the start of the visit to the Official US Time 
using www.time.gov or to an equivalent atomic clock. 
The study devices do not all automatically adjust for daylight savings time. Subjects 
should not adjust the study device times on their own – they should wait until someone 
at the clinic can adjust the time so any offsets can be documented in order to reconcile 
the data.
4.3.2
MEDICATIONS AND MEDICAL SUPPLIES
All medications and medical supplies required for the Clinical Research Center (CRC) 
hypoglycemia and hyperglycemia treatment protocols will be readily available at the time 
of subject treatment including a code cart. The subject will be rescheduled if he/she did 
not bring his/her required medications or appropriate medications are not available at 
the clinic.  
4.3.3
SUBJECT ADMISSION
The subject will arrive at the clinic and the following tests will be performed to confirm 
eligibility for participation in the visits:
!
Hematocrit will be assessed using local lab or Point of Care testing device. Subject 
must be within reference range to participate in accuracy visit.
!
Female subjects of childbearing capacity will perform a urine pregnancy test. If 
positive, the subject will discontinue study participation. Subject withdrawal will be 
documented.
!
Study subjects using tetracyclines within 4 days of visit start will be asked to 
reschedule the visit. 
!
Study subjects using sorbitol/mannitol within 12 hours of visit start will be asked to 
reschedule the visit. 
!
The study team will confirm the absence of a febrile or vomiting illness within 24 
hours of the admission.
!
The study team will confirm that the subject brought his/her personal insulin and 
insulin pump or injection supplies (as applicable) and regular medications. The subject 
will continue to use his/her diabetes treatment regimen throughout the admission. 
The subject will be rescheduled if he/she did not bring his/her regular medications or 
appropriate medications are not available at the clinic. 

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!
Clinical staff to confirm that the subject is wearing the transmitter and that the 
transmitter and hand-held device are in communication and functioning.
!
The subject will be rescheduled if he/she did not bring his/her Transmitter and cannot 
make them available during the visit.
If all admission readiness criteria are not met, the subject will be rescheduled. If all of the 
admission readiness conditions are met, the subject will be admitted to the Clinical 
Research Unit.
4.3.4
ADVERSE EVENTS
Upon admission subject will be asked about any adverse events or changes in medication 
since the last study visit. If subjects experienced DKA or Severe hypoglycemia during the 
past 30 days, they will be excluded from participating in the glucose challenge, but may 
continue with the accuracy visit under observation only. The sensor insertion site will be 
examined. Adverse events including those associated with the insertion site will be 
documented on the appropriate eCRF.
4.3.5
KETONE TESTING
Ketone (β-hydroxybutyrate (β-HOB)) measurements will be made using a study supplied 
FDA-approved self-monitoring ketone meter and strips as described in 5.2.3. Subject 
blood ketones should be evaluated from capillary or venous blood using the ketone 
meter while in the clinic for sensor insertion and accuracy visits at the following times:
!
On arrival and at discharge from the clinic 
!
Glucose ≥300 mg/dL (measure approximately within 20 minutes of the first glucose 
reading >300 mg/dL and repeat approximately every 60 minutes until < 300mg/dL)
!
Ketones  ≥0.6 mmol/L (repeat approximately every 60 minutes until < 0.6 mmol/L)
!
Subject has nausea, vomiting or abdominal pain regardless of glucose level.
Treatment guidelines for ketones can be found in section 7.5.3.
4.3.6
SMBG TESTING
During in-clinic days, subjects should continue testing blood glucose using the study-
supplied Subject SMBG Meter following the schedule for each visit (hourly). For home use 
periods, it is requested that subjects test approximately 7 times per day (before meals, 2 
hours after meals, and at bedtime). Subjects will be requested to enter all SMBG readings 
into the Eversense® app as glucose events. Subjects will be monitored for compliance to a 
minimum of 4 SMBG readings per day including at least one pre-prandial and one 
bedtime reading, and will be contacted by the study site if they are found to be out of 

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compliance. Subjects will be requested to enter all insulin injections/boluses into the 
Eversense app to aid in evaluation of subject compliance with adjunctive use of the CGM 
system.
All fingersticks for capillary blood glucose testing will be preceded by hand washing (with 
soap, warm water and a dry towel), or by using an alcohol swab and allowing the area to 
air dry.
4.3.7
SYSTEM CALIBRATION
The Eversense® 180 Continuous Glucose Monitoring (CGM) System (primary sensor) will 
be calibrated and maintained per Eversense® 180 CGM User Guide. After the initialization 
period (approx. 30 hours after sensor insertion), the system enters the Daily Calibration 
phase. For this study, subjects should follow the recommendations below:
4.3.7.1
IN CLINIC
During the in-clinic sessions, subjects will calibrate as prompted by the Eversense® 180 
CGM System.  
4.3.7.2
AT HOME
During periods of home use, it is required to calibrate the Eversense® 180 CGM System 
using SMBG values from the study-supplied meter, the Contour Next One blood glucose 
meter. Calibration is best done when glucose is neither rapidly rising nor falling.  The 
Eversense® 180 CGM System will prompt the user when it is time to calibrate.
4.3.8
USE OF STUDY DEVICES FOR DIABETES TREATMENT
For the duration of the study, all diabetes care decisions will be based on reference blood 
glucose values or SMBG as appropriate, rather than Eversense® 180 CGM System results.
4.3.9
IV/BLOOD DRAW GUIDELINES
4.3.9.1
IV PLACEMENT/SETUP
IVs for blood sampling may be placed in the arm or hand. IV Access will be maintained 
during the sampling portion of the study for blood sampling and for the treatment of 
severe hypoglycemia or hyperglycemia during the study. If an IV fails, a reasonable effort 
should be made to replace it.
It is advised that sites use a heating pad in order to help keep IV sampling sites patent and 
improve blood flow.

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4.3.9.2
TIMING OF BLOOD SAMPLING
Blood will be sampled approximately every 5 to 15 minutes, dependent on the value of 
the previous sample according to the following ranges:
!
BG ≥ 300 mg/dL: every 5 minutes (+/- 2 minutes) *
!
BG >70 mg/dL and < 300 mg/dL: every 15 minutes (+/- 2 minutes)
!
BG ≤70 mg/dL:  every 5 minutes (+/- 2 minutes)
*When > 400 mg/dL, sampling may be reduced to every 15 minutes 
Blood sampling can also be reduced to every 15 minutes after the challenge is met. 
Additional samples may be drawn for YSI glucose analysis as needed for patient safety or 
to recheck a suspected erroneous value (e.g. dilute sample).
In the event of loss of IV access or loss of functional YSI and need for continued subject 
monitoring, glucose measurements will be made on capillary whole blood using the 
Subject SMBG meter as needed. 
Samples missed due to loss of IV access or other interruptions will not be considered 
protocol deviations.   
4.3.9.3
SAMPLE VOLUME
Approximately 0.5 ml IV blood samples will be collected (after 1.5 ml waste is cleared 
from sampling apparatus) in sample containers with an appropriate anticoagulant 
additive (BD Microtainer K2E tubes (REF 365955) or Sarstedt Monovette with K2E (REF 
06.1664.001) or similar) for analysis. 
4.3.9.4
CENTRIFUGE
Centrifuge sample to sufficiently separate the plasma, approximately 30 seconds in 
StatSpin Express 2 (or similar) centrifuge (8500 rpm).
Samples centrifugation should begin as soon as possible after the blood draw (within a 
maximum of 3 minutes).   Samples should be discarded if not run within this time frame.
4.3.10 GLUCOSE CHALLENGES
4.3.10.1 SUBJECT ELIGIBILITY 
Subjects not on insulin therapy will not be expected to undergo hypoglycemic challenges.  
Eligible subjects will be required to participate in glucose challenges. Subjects unable to 
participate in glucose challenges will participate in the accuracy sessions using free range 
glucose control.

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4.3.10.2 GUIDELINES FOR DETERMINING WHICH CHALLENGE TO CHOOSE (ALL VISITS)
Subject BG levels and direction of those levels determined using the first three SMBG/YSI 
readings will inform whether the subject will participate in the hypoglycemia or 
hyperglycemia challenge on that study day, according to the following table as a 
guideline:
Glucose level
Challenge*
<180 mg/dL
Hypoglycemia challenge
≥180 mg/dL
Hyperglycemia challenge
*Investigator discretion and patient safety will also be considered 
in determining appropriate challenge. Additional SMBG can be done to determine the 
appropriate challenge.
4.3.10.3 INITIATING THE GLUCOSE CHALLENGE
Hyperglycemia challenges may be initiated by administering a mixed meal of (30 to 40%)
carbohydrate content gradually targeting maintaining a glucose level of >300 mg/dL for 
75 minutes, based on subject’s insulin/carbohydrate ratio. Liquid carbohydrates (such as 
Boost, soda, juice) can be given in small volumes only if the mixed meal is not successful 
in reaching the target.  Hypoglycemia challenges may be initiated by administrating SQ 
fast-acting insulin targeting maintaining <70 mg/dL for 1 hour, based on subject’s insulin 
sensitivity ratio. Details about all carbohydrates (time, type and amount) will be recorded 
for entry into the study database, as well as all bolus insulin given.
4.3.11 DOWNLOADING DEVICES
The study issued Subject SMBG meter and the Transmitter(s) will be downloaded at the 
end of each sensor accuracy visit (Days 1-180 visits), during each clinic visit for subjects in 
the cohort continuing to 365 days, or at any unscheduled visit as appropriate. Transmitter 
data will also be uploaded to a data management system to monitor calibration 
compliance. Additionally, for the subjects continuing to 365 days of sensor wear with the 
secondary sensor and a new primary sensor, accuracy of the new 180 day primary sensor 
will be monitored for performance approximately every 2 weeks.  Since the compliance 
monitoring of the daily SMBG entry will continue on for the second primary sensor, the 
performance monitoring with use entered SMBG points to assess that the accuracy is 
within the distribution of the 20/20% agreement per day from the PRECISE II study
throughout that two week monitoring interval. If performance is not restored to within 
the PRECISE II distribution within 2 weeks, the 180-day sensor will be placed in blinded 

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Clinical Mode for the remainder of the study. The subject will be blinded to glucose values, 
alerts and alarms.
4.3.12 HbA1c BLOOD DRAW
Blood samples will be drawn for HbA1c measurement at the 90-day, 180-day, and 
365-day visits, as applicable. All samples will be collected and processed as 
described in the instructions provided by the central lab.
4.3.13 QUESTIONNAIRES
At visits 8 (Day 90 visit), 11 (Day 180 visit), and 15 (Day 365 visit) subjects will 
complete the Diabetes Distress Scale questionnaire. At the removal visit, subjects 
will complete the CGM Satisfaction questionnaire. Subjects who have a sensor enter 
Clinical Mode prior to the designated visits, the Diabetes Distress Scale 
questionnaire and CGM Satisfaction questionnaire may be completed at the visit 
following confirmation of Clinical mode.
4.3.14 DISCHARGE INSTRUCTIONS – SENSOR ACCURACY VISITS
The discharge procedure will occur upon completion of visit related activities. Blood 
glucose (either SMBG or YSI) and ketone measurements will be assessed. If the glucose 
level is <75 mg/dL or >300 mg/dL, corrective action will be taken by the investigator.
Subjects may be discharged when they have had 2 glucose readings taken at least 15 
minutes apart that are >75 and < 300 mg/dL. Ketones should be ≤1.5mmol/L. Site will 
document any adverse events that may have occurred during the visit.
Additional inpatient time for BG stabilization will not be considered an adverse event or 
protocol deviation.
Subjects will be provided a standard meal or snack as necessary prior to release to 
prevent post-discharge hypoglycemia. Snacks will be available in the clinic for subjects to 
take with them on the ride home.
A clinician trained in the treatment of diabetes should also discuss and make 
recommendations about each subject’s insulin regimen for the remainder of the day to 
prevent post-visit rebound hypoglycemia which can occur 12 hours later.
4.3.15 ESTIMATED TOTAL BLOOD VOLUME
Approximately 43-51 blood samples will be obtained throughout the course of each of 
the respective visits in addition to the blood samples (2 ml) required for HbA1c analysis
(as required) and fingersticks. The estimated amount of blood for each accuracy visit is 
approximately 2 ml per sample, exclusive of lab draws.

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4.3.16 ESTIMATED VISIT DURATION
The total duration of the inpatient visit is approximately 10-12 hours depending on the 
visit.  The study time may be extended for glucose stabilization prior to discharge.
4.4
SENSOR REMOVAL
All sensors will be removed approximately 180 days post insertion. Removal of the 
Sensor may also be scheduled after the Day 180 accuracy visit if more convenient for 
subject and clinicians. Sensor removal before or after the specified visit will not be 
considered a protocol deviation provided that removal is performed no longer than 189 
days post-insertion and Visit removal procedures/activities are followed. 
Subjects will be asked to complete Diabetes Distress Scale and CGM Satisfaction
questionnaires related to their experiences at the end of sensor wear period.
Prior to Sensor removal, the Investigator will assess the Sensor location visually as well 
as by palpation. The Sensor will be removed following the procedure in the Eversense®
CGM Sensor Insertion and Removal Instructions.
The removed Sensor(s) will be handled in compliance with institution/regulatory 
requirements for biomedical waste, and will be returned following Eversense®
instructions, using the provided Biohazard Return Kit.
4.4.1
Day 180 Sensor Removal and Insertion (2 Sensor Subjects)
For subjects with 2 sensors, only the primary sensor will be removed approximately 180 
days post insertion. A new Eversense 180 sensor will be inserted in the same arm. The 
secondary sensor will remain in situ. The Investigator will determine if the initial incision 
created for the removal of the primary sensor is adequate for the insertion of the new 
sensor per recommendations of Deiss D, et all13. Based on Investigator discretion, a new 
incision and insertion location may be used for placement of the new sensor. Based on 
recommended practices, durable performance of multiple sensor cycles is expected 
with consecutive insertions14,15. Both sensors will be removed 365 days post insertion of 
the secondary sensor. Sensor removal before or after the specified visit will not be 
considered a protocol deviation provided that removal is performed no longer than 374
days post-insertion for the secondary sensor and Visit removal procedures/activities are 
followed.   

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4.5
POST-SENSOR REMOVAL FOLLOW UP, VISIT 12 AND VISIT 16
Subjects will return to the clinic approximately 10 days following Sensor removal (sensor 
removal date +7 to +17 Days). The healing of the Sensor site will be evaluated at this 
planned final visit. If there is a concern by the investigator about healing of the Sensor
site, the subject will be asked to return to the clinic in approximately 10 days, and
followed until resolution. Any adverse event would be reported. Clinicians may request 
photographic images as part of the follow-up process if subjects are unable to return to 
the clinic.
Subjects will exit the study after the Follow-up Visit 12 is completed as above. The subset 
of subjects with 2 sensors completing additional visits 13-15 will exit the study after 
Follow-up Visit 16. Subjects will continue to follow their diabetes care routine according
to their health care provider recommendations.
5
GENERAL CONSIDERATIONS FOR STUDY VISITS
5.1
DEFINITION OF ENROLLMENT
A subject is considered enrolled in the clinical trial after he or she has provided informed 
consent.
Subjects who fail one or more of the eligibility criteria are considered screen failures.
Subjects who withdraw consent or are withdrawn by the investigator after enrollment
and prior to the first Sensor insertion attempt are “withdrawn prior to Sensor insertion”
and are withdrawn from the study without data acquisition. A listing of screen failures and 
“withdrawals prior to Sensor insertion” subjects including the reason for study exit will be
reported.
Subjects who begin a first Sensor insertion procedure (defined as injection of local
anesthetic) remain enrolled in the study and will be analyzed as evaluable subjects per the
description of study populations in Section 11 Statistical Methods.
5.2
MEASUREMENT DEVICES– MAINTENANCE/CONTROL TESTING
Study equipment (bedside YSI glucose analyzer, ketone meter and study-supplied (SMBG) 
meter) are described in detail below. 
5.2.1
BEDSIDE YSI
The primary instrument for plasma glucose measurements is the YSI glucose analyzer 
(2300 Stat Plus Glucose & Lactate Analyzer, Yellow Springs Instruments, Yellow Springs, 

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OH, USA).  Manufacturer instructions for operation, calibration, quality control, and 
maintenance will be followed.
5.2.2
SUBJECT SMBG METER
The study will supply and use a widely-used, commercially available FDA-approved self-
monitoring blood glucose (SMBG) meter and strips. Control solution testing of the 
meter/strips will be verified with the control solution(s) specific to the meter and strips. 
The tested control solutions must read within the established range on the glucometer 
strips per manufacturer labeling in order to be used in the study. Manufacturer 
instructions for operation and quality control will be followed. Subjects will be advised to 
perform control solution testing each time a new package of strips is deployed, or any 
time the subject suspects improper performance of the meter.
5.2.3
KETONE METER
The study will supply and use an FDA-approved self-monitoring ketone meter and strips 
(Abbott Precision Xtra or similar), which will measure β-hydroxybutyrate (β-HOB). Ketone 
meters will remain at the clinical site (not disbursed to the subject). Calibration of the 
ketone meter will be verified with the control solution(s) specific to the meter and strips. 
The tested control solutions must read within the established range on the strips per 
manufacturer labeling in order to be used in the study. Manufacturer instructions for 
operation and quality control will be followed.
5.3
SENSOR REPLACEMENT
Primary sensors that fail within 30 days of sensor insertion will be replaced at an 
unscheduled visit.  Subjects will continue to follow their originally scheduled visits. 
5.4
PRIMARY SENSOR BLINDING
During the study the primary system may go into a “blinded mode” (called Clinical Mode 
by the device). Under these circumstances subjects will continue to wear the system, and 
enter calibrations (as prompted) and SMBG values, but the system will not provide sensor 
glucose information or glucose related alerts. Subjects should continue with all remaining 
sensor accuracy visits with the blinded system. 
If a primary sensor displays a “sensor replacement” alert, it (and the secondary sensor if 
applicable) will be removed at an unscheduled visit, and the subject will be withdrawn.
5.5
SPONSOR PRESENCE AT VISITS 

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One or more technical representatives of the sponsor may be present during clinic visits
under supervision of the Clinical Investigator.
5.6
PHOTOGRAPH/VIDEOGRAPHY
The procedure for inserting or removing the sensors may be photographed and/or 
recorded on video after receiving subject authorization in writing. Only the area 
immediately nearby the sites will be photographed and/or recorded and subjects will not 
be identifiable.
At the discretion of the study Sponsor and primary investigator, at any visit, the locations of 
the devices may be documented for safety reasons through a variety of means including,
but not limited to, photography, x-ray, and ultrasound examination.
6
CLINICAL LABORATORY EVALUATIONS AND ESTIMATED BLOOD VOLUMES
Standard clinical laboratory analysis equipment, procedures and quality control will be used
for all laboratory evaluations in this clinical trial. Blood samples will be drawn for glycemic 
challenges and for laboratory measurement of HbA1c.  Blood loss will not exceed the 
American Red Cross Guidelines of more than 475 ml over any 8-week period. Hematocrit will 
be assessed using local lab or Point of Care testing device. 
7
SUBJECT SAFETY, STOPPING RULES, AND STUDY EXIT
7.1
DIABETES AND SAFETY CONSIDERATIONS DURING CLINIC VISITS
Diabetes care in the Clinic Visit will be the responsibility of the Investigator and
appropriately delegated staff. As diabetes self-management is an integral part of 
diabetes care, the Investigator may work closely with the Study subject, when
appropriate, to determine the best approach, however the ultimate responsibility lies
with the Investigator.
7.2
MEDICAL OVERSIGHT
There will be staff trained in emergency response, and there will be an EKG and emergency
cart available at the site at all times.  Site-specific safety guidelines will be utilized for
subject safety management during periods of hyperglycemia (including monitoring blood
ketones) and hypoglycemia. Study staff (MD, DO, PA or NP who has experience in 
diabetes management) will also be immediately available at all times during hypoglycemia

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and hyperglycemia challenges. A nurse, nurse practitioner, or physician/PA will be at the
bedside or on the unit throughout the entire visit.
7.3
SENSOR SITE
The sensor insertion sites will be assessed (visually, as well as by palpation, and by eliciting 
Subject history) at each clinic visit, and the Subject will be instructed to call the clinic if 
signs or symptoms of irritation or infection (increased temperature, pain, redness, 
warmth, swelling, or purulence) are observed at any time.  Sensor site infections are to be 
treated with antibiotics, either topical or oral.
At any time during the study, if the study physician determines that there is an infection at 
the sensor insertion site that has not responded to treatment within 3 days, the sensor will 
be removed. In the event of an insertion site infection and sensor removal in a subject 
with one sensor only, the subject will be withdrawn from the study and not replaced. In 
Subjects with two sensors, if the primary sensor is removed due to infection, the other 
sensor will become the primary sensor.
7.4
OTHER CONSIDERATIONS AND SAFETY ASSESSMENTS
!
An assessment and documentation of adverse events occurring in clinic and during
home use will be on-going.
!
Urine pregnancy testing (for women of childbearing potential) will be performed at the 
start of visits as scheduled with study exit as described in section 7.6.5 if the Subject is
pregnant.
!
Subjects will arrive at Clinic Visits, having followed their usual diabetes care,
including insulin dosing and food.
!
Subjects must not be febrile in the 24 hours prior to Clinic Visits 2-15.
!
IV access is required during most clinic visits. In the event of loss of IV access,
glucose measurements may be made using Subject SMBG meter or alternate
sampling method for subject care. Investigator may determine when further
attempts at IV access will cease.
!
In order to prevent adverse effects that may occur as a result of the hyperglycemia 
challenge, unlimited sugar free oral fluids should be provided to subjects to prevent 
dehydration secondary to hyperglycemia.
7.5
HYPOGLYCEMIA 
The Subject will be asked to alert the study team anytime he or she experiences
symptoms of hypoglycemia (i.e., shakiness, dizziness, sweating, headache, moodiness,

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difficulty concentrating, or the Subject’s usual symptoms of hypoglycemia). The
symptoms will be confirmed by Subject SMBG Meter and/or YSI.
Intravenous access is to be maintained during the Clinic Visit and available for
hypoglycemia treatment as indicated. Glucagon by injection and IV dextrose will be 
available at the site and may be used as clinically indicated. A heating pad or heating 
chamber may be used during the session to minimize potential for occlusion or to 
enable the insertion of the IV.
7.5.1
GUIDELINES FOR TREATMENT FOR HYPOGLYCEMIA WHEN NOT IN A CHALLENGE 
PERIOD
Subject safety prevails, and Investigator may treat for hypoglycemia when clinically
indicated at any time.  However, when the subject is not in a challenge and becomes 
hypoglycemic and safety is a concern, the guidelines below should be followed to treat 
the hypoglycemia.
Glucose level
Glucose administration
Safety
<60 mg/dL
Treat hypoglycemia as 
appropriate using oral 
carbohydrates such as glucose 
tablets (~15 g. and check glucose 
in 15 minutes minimum, repeat) 
until BG >60 mg/dL
If subject is unable to ingest 
glucose orally, IV dextrose 
(~2-3 mL/kg D10 intravenous 
or up to 30 ml D50%) may be 
used. Glucagon will be 
available for emergency.
60 – 75 
mg/dL
Treat hypoglycemia as 
appropriate using oral 
carbohydrates such as glucose 
tablets (~10 g. and check glucose 
in 15 minutes minimum, repeat) 
until BG >75 mg/dL
!
Risk for severe hypoglycemia is defined as any of the following situations:
o
Glucose <50 mg/dL
o
The subject is unable to cooperate with oral treatment of hypoglycemia
o
The glucose is dropping at a rate that may not respond adequately to oral 
treatment
o
The subject experiences symptoms of neuroglycopenia (e.g. lethargy, 
disorientation, confusion [disordered processing of information or 
communication], or inappropriate behavior) 

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o
The subject experiences symptoms of severe hypoglycemia (i.e. hypoglycemic 
seizure or loss of consciousness) 
!
In the event that there is NO intravenous access and the subject is at risk for severe 
hypoglycemia (as defined above), the subject will be treated with 1 mg of glucagon 
subcutaneously or intramuscularly. 
o
The drug will be reconstituted and administered per package 
insert/instructions. 
o
Glucagon may be repeated as needed every 20 minutes to achieve glucose level 
≥75 mg/dL. Once the subject is able to consume oral treatment, the subject will 
be treated orally with fast acting carbohydrate as needed until a glucose level of 
≥75 mg/dL is achieved. Orange juice and milk will be avoided after glucagon 
administration. 
o
Attempts will be made to reestablish intravenous access. 
!
The accuracy visit will be stopped if the subject experiences a hypoglycemic seizure 
or loss of consciousness and only safety procedures will be continued. The study 
physician/PA or nurse practitioner will take control over glucose sampling decisions 
in order to stabilize the subject’s glucose between 100-300 mg/dL and determine 
the appropriate subject disposition (i.e. home or medical facility). 
7.5.2
HYPERGLYCEMIA AND BLOOD KETONE MONITORING
The Subject will be asked to alert the study team anytime he or she notes symptoms of 
hyperglycemia (i.e. thirst, increased urination, or other symptoms). A glucose level will be 
confirmed by YSI or Subject SMBG meter.
Fingerstick blood ketones, using a commercially available ketone meter, will be 
monitored if blood glucose ≥300 mg/dl hourly until resolved. If glucose >400 mg/dl and 
no symptoms and no ketones, the cause of the hyperglycemia will be investigated and 
treated as appropriate by the Investigator.
If blood ketones > 1.5 mmol/L; subject participation in glucose challenges will be stopped
for the day (see below). Appropriate care will be provided, including fluids and insulin
as determined by Investigator. Standard-of-care troubleshooting for insulin pump users
will take place, including change of infusion set if indicated and insulin by injection if
indicated. If the subject's home parameters are not felt to be working adequately due 
to hyperglycemia, ketonemia, or other factors (e.g. intercurrent illness), the study MD 

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or NP will administer corrective insulin either via insulin syringe or via a new pump site 
using an ISF determined to be appropriate for the setting and a goal glucose of 120 
mg/dL. The subject will continue to be monitored until a glucose level between 100-300 
mg/dL and ketone measurement <0.6 mmol/L has been achieved (or the subject is 
discharged to an appropriate medical team).
7.5.3
GUIDELINES FOR TREATMENT OF HYPERGLYCEMIA AND KETONES WHEN NOT IN A 
CHALLENGE
Subject safety prevails, and Investigator may treat for hyperglycemia when clinically
indicated at any time.  However, when the subject is not in a challenge and becomes 
hyperglycemic and safety is a concern, the guidelines below should be followed to treat 
the hyperglycemia. 
Ketone
BG
<0.6
0.6-1.5
>1.5
<300
• Ketone testing will be 
repeated hourly until <0.6
• Subject will be treated with 
SQ or IV insulin targeting 
120mg/dL using subject’s 
insulin sensitivity factor
• Glucose challenges will be stopped, 
and subject will enter free range 
glucose control
• Ketone testing will be repeated 
hourly until <0.6
• Subject will be treated with SQ or 
IV insulin targeting 120mg/dL using 
subject’s insulin sensitivity factor
>300
• Ketone testing will be 
repeated hourly until 
BG <300
• Ketone testing will be 
repeated hourly until <0.6
• Subject will be treated with 
SQ or IV insulin targeting 
120mg/dL using subject’s 
insulin sensitivity factor
• Continue monitoring until 
BG <300
• Glucose challenges will be stopped, 
and subject will enter free range 
glucose control
• Ketone testing will be repeated 
hourly until <0.6
• Subject will be treated with SQ or 
IV insulin targeting 120mg/dL using 
subject’s insulin sensitivity factor
• Continue monitoring until BG <300
!
Insulin treatment for hyperglycemia or ketones should be done using the subject’s 
own insulin. In the event that the subject’s own insulin appears to be compromised 
(not having the expected effect on the subject’s blood glucose), appropriate insulin 
(based on the subject’s normal insulin type and concentration) provided by the site 
may be used.

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7.6
SUBJECT STOPPING RULES
7.6.1
STOPPING CHALLENGES – REATTEMPT IN FUTURE GLUCOSE CHALLENGES 
Glucose challenges will be stopped, and subject will enter free range glucose control if:
!
Subject requests to end the challenge due to discomfort (desires food and/or 
insulin)
!
Subject ketone measurement >1.5 mmol/L 
These subjects will be eligible to continue participating in challenges at future accuracy 
visits. Blood sample collecting and analysis on YSI will continue during this time.
7.6.2
STOPPING CHALLENGES – NO RE-ATTEMPT IN FUTURE GLUCOSE CHALLENGES
!
Subject develops significant nausea, vomiting, abdominal pain, chest pain, or 
develops ketoacidosis
!
The subject is unable to cooperate with oral treatment of hypoglycemia
!
The glucose is dropping at a rate that may not respond adequately to oral 
treatment, and the administration of glucagon is required
!
The subject experiences symptoms of neuroglycopenia (e.g. lethargy, 
disorientation, confusion [disordered processing of information or 
communication], or inappropriate behavior) 
7.6.3
STOPPING ACCURACY VISIT
During accuracy visits, study procedures other than those required for subject safety will
be stopped for that day if any of the following occur:
!
The subject had a serious adverse event that is deemed either related to study 
or in the investigator’s opinion requires stopping
!
Medical intervention is required to treat severe hypoglycemia (seizure,
unconsciousness, etc.)
!
Adequate intravenous access cannot be maintained
!
The YSI and back-up YSI, (if available), stop functioning and neither can be re-
established within 2 hours.
!
Subject requests to stop
!
Investigator determines it is in Subject’s best interest to stop the accuracy visit

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!
Subject develops DKA
7.6.4
SUBJECT WITHDRAWAL
Subjects will be withdrawn from the study if:
!
Subject is noted to be pregnant 
!
The subject may withdraw if he/she had a serious adverse event that is 
deemed either related to study device or procedures 
!
Subject voluntarily withdraws from study
!
There is an infection at the sensor insertion site that has not responded to 
treatment within 3 days and subject has only one functional sensor 
!
Subject develops more than one instance of DKA or more than one 
instance of severe hypoglycemia which require stopping an accuracy visit.
!
Investigator determines it is in Subject’s best interest to withdraw.
!
Subject is lost to follow-up
!
Subject dies
7.6.5
STUDY EXIT
A Subject’s participation is considered complete after the follow-up Visit post-Sensor 
removal. A Subject may choose to withdraw at any time without adverse effect on their 
care. The subject will continue with their medical follow-up, according to standard-of-
care. The reason for study withdrawal will be documented.
In the event that a subject withdraws from the investigation or is lost to follow-up, the 
Investigator will make all reasonable efforts to locate a Subject and encourage Subject 
to return for Sensor removal. If a subject is lost to follow-up, three separate telephone 
calls should be made to attempt to schedule a follow-up visit or obtain follow-up 
information. All attempts and contacts should be documented in the source documents. 
The subject’s Primary Care Physician may also be contacted as stated in the Informed 
Consent Form.  If the Subject does not respond to the three telephone calls, then the 
Investigator will send a certified letter to the Subject. The Subject will be considered lost 
to follow-up if this communication is unsuccessful.  
7.6.6
REPLACEMENT OF SUBJECTS
Subjects who exit the study prematurely may not re-enter the study and will not be

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replaced.
7.7
STUDY STOPPING RULES
Senseonics may choose to suspend or prematurely terminate the investigation for the
following reasons:
!
Subject safety issue
!
More than 3 subjects require withdrawal from the study due to Severe hypoglycemia 
or DKA
!
Production limitation
!
Administrative decision
The Medical Monitor will review adverse events on a scheduled periodic basis as outlined 
in Section 13.13. In the case of device-related serious adverse events, the Medical
Monitor will consult with the Sponsor and Principal Investigator if appropriate to ensure
that the necessary steps are taken to protect the safety and well-being of the Subjects.
In the event that that study is stopped, the Investigator will promptly inform the Subjects
and ensure appropriate therapy and follow-up, including Sensor removal.  Additionally,
the investigator will promptly inform the IRB and provide a detailed written explanation.
The pertinent regulatory authorities will be informed according to local regulations.
7.8
TERMINATION OF INVESTIGATOR OR INVESTIGATIONAL SITE
Senseonics reserves the right to terminate an investigator/investigational site for any of 
the following reasons, which are considered major deviations:
!
Failure to secure subject informed consent including protection of personal data
prior to enrollment
!
Failure to report unanticipated adverse device effects and serious adverse events 
to Senseonics and to the IRB within its required reporting time after learning of
the event
!
Repeated investigational plan deviations
!
Loss of or unaccounted for investigational product inventory.
8
RISK AND BENEFIT ANALYSIS
8.1
POTENTIAL BENEFITS

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Studies have shown that real-time CGM use improves patients overall glycemic control.10
Improved glycemic control may not be achieved by all subjects. However, subjects are
contributing to the overall advancement of medical and scientific knowledge that may
benefit future subjects with similar conditions. The CGM data collected will not be used
for any clinical decisions or care.
8.2
POTENTIAL RISKS
The Eversense® CGM System has been approved for measuring interstitial fluid glucose for 
up to 90 days by FDA in June 2018. However, the Eversense® 180 CGM System for 
measuring interstitial fluid glucose for up to 180 days is considered investigational in the 
United States. To evaluate the Eversense® 180 CGM system, blood draws for glucose 
measurements will be performed more frequently than in daily routine. In addition to 
use of the System, hyperglycemia and hypoglycemia challenges may be performed
exclusively for study purposes.
8.3
ANTICIPATED ADVERSE EFFECTS
The following adverse effects could occur in association with insertion, removal, and/or
use of the Eversense® 180 CGM System Sensor and/or Transmitter:
•
Infection, local or systemic, possibly resulting in sensor removal
•
Excessive bleeding during insertion or removal
•
Bruising or swelling
•
Poor wound healing after insertion or removal
•
Keloid and/or scar formation
•
Excessive or prolonged pain or discomfort at the Sensor site
•
Nerve damage causing tingling, numbness, pain or weakness
•
Uncomfortable heating
•
Burn
•
Electrostatic shock
•
Skin irritation and/or redness
•
Itch
•
Discoloration of skin
•
Skin thinning
•
Hematoma formation
•
Device migration
•
Skin erosion

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•
Allergic reaction to the device components, local anesthetic, or other medication or
materials used in the procedure
•
Anxiety and/or nervousness and/or lack of sleep
•
Device fragments or particulate matter remaining in the body
•
Failure to retrieve device or device left behind
•
Difficulty in removing device that may require surgery
•
Device malfunctions of the Sensor and/or Transmitter with possible need to
remove and/or replace the Sensor and/or Transmitter
•
Burning sensation or pain.
•
Elevated blood pressure
•
Water retention in the tissue, swelling or edema
•
Airway spasms
•
Shortness of breath
•
Circulatory disorders
•
Confusion
•
Disorientation
•
Increased or decreased sensitivity to touch or pain
•
Metallic taste
•
Sleepiness
•
Visual disturbances and/or blurred vision
•
Tinnitus
•
It is possible that the local anesthetic could cause a reaction other than listed or 
previously seen.
•
Fluid/electrolyte disturbances such as fluid retention
•
Muscle weakness
•
Osteoporosis
•
Peptic ulcer
•
Pancreatitis
•
Ulcerative esophagitis
•
Impaired wound healing
•
Headache
•
Psychic disturbances and mood swings
•
Convulsions
•
Glaucoma

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•
Weight gain
•
Nausea and/or vomiting
•
Malaise
•
Irritability
•
Insomnia
•
Heartburn
•
Hyperglycemia
•
Ketosis
•
Headaches
•
Dizziness, lightheadedness, and/or fainting
•
It is possible that the use of the Eversense® 180 CGM system could cause a reaction
other than listed or previously seen.
•
It has not been determined whether the risks usually associated with injectable 
dexamethasone apply to the use of dexamethasone elution ring, a highly localized,
controlled-release device.
•
The dexamethasone ring could cause other adverse events not listed or previously
seen.
•
Other adverse events typically related to diabetes treatment and diabetes are 
unknown
8.4
RESIDUAL RISKS ASSOCIATED WITH THE INVESTIGATIONAL DEVICE
Components of the Eversense® 180 CGM System are manufactured under the Quality 
System provisions of ISO 13485:2016.
Risk analysis has been performed and adequate control put in place as prescribed in
relevant provisions of IEC 62304, ISO 14971, and IEC 60601-1, in accordance with the 
requirements of ISO 13485:2016. Residual risks associated with the device included risks
in the categories of electromagnetic and thermal energy, biocompatibility, biologic,
chemical and mechanical factors, and user-related error.  All identified risks have been
reduced as far as possible using various control methods including software revision and re-
validation, hardware design modification, packaging and sterilization process validation
and labeling revision. The calculated residual risks were determined to be acceptable for
conduct of this clinical investigation.
8.5
RISKS ASSOCIATED WITH PARTICIPATION IN THE CLINICAL INVESTIGATION

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This clinical investigation involves subjects with diabetes mellitus. These subjects may
experience hyperglycemia and hypoglycemia as a consequence of their existing
condition and medical management (e.g. insulin administration). For this study,
hyperglycemia and hypoglycemia will not be reported as adverse events unless meeting
criteria of a Serious Adverse Event. Episodes of hyperglycemia and hypoglycemia as 
documented by the Subject SMBG Meter will be reported in an extra listing separate
from the AE listings. Should a known side effect(s) occur to administered medication(s)
used in the intervention, such effects will be reported as part of the adverse event
description and will not be considered a separate adverse event.
The amount of blood drawn for in-clinic testing during the study is below the
acceptable limits of blood donation of approximately 475 mL per 8 weeks; hence it does
not pose any additional unacceptable risk to the subjects.
This clinical investigation involves the following procedures that present risk:  placement
of an intravenous catheter, frequent blood sampling, and conduct of hyperglycemia and 
hypoglycemia challenges at the clinic visits. In addition, Subjects in this study may use an
insulin pump or syringes to administer subcutaneous insulin.
The following risks are potentially associated with such procedures:
!
Routine administration of insulin may cause hematoma, redness, swelling and itch at 
the injection site, skin rash, itch, sweating, gastro-intestinal complaints, edema,
difficulty breathing, palpitations and drop in blood pressure, and even death.
!
Hypoglycemic symptoms requiring medical intervention which may
include seizures, neuroglycopenia, coma and even death (including
occurrence during home use)
!
Insulin administration leading to hypoglycemia include: cold sweating, cool and
pale skin, fatigue, nervousness, shakiness, anxiety, weakness, confusion, feeling
of numbness, hunger, impairment of vision, problems with concentration,
headache, nausea, palpitations, coma, or death.
!
Hyperglycemia and diabetic ketoacidosis requiring medical intervention which may
include potential complications such as nausea, vomiting, abdominal pain,
dehydration, difficulties with breathing, confusion, bad breath, low blood pressure,
coma, kidney failure, cardiac arrhythmia, myocardial infarction, cerebral edema,
rhabdomyolysis and even death (including occurrence during home use).
!
Excessive pain during insertion of the IV catheter
!
Multiple sticks due to IV placement

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!
IV placement failure
!
Restricted mobility
!
Fainting, dizziness, lightheadedness or low blood pressure in response to blood 
sampling
!
Bleeding during catheter insertion or infusion pump infusion set change
!
Bruise formation at catheter site or due to infusion pump use
!
Fluid overload due to saline flushes of IV catheter
!
Skin redness or scarring due to infusion pump use
!
Temporary muscle or nerve irritability, arrhythmia or death due to electrolyte 
disturbance
!
Tissue damage (burn) due to heating devices
!
Severe gastro-intestinal distress
!
Difficulty breathing
!
Cardiovascular symptoms
!
Nerve damage
!
Rash
!
Pain
!
Infection, local or systemic
!
Blood clots, which may cause inflammation, swelling and pain
!
Circulatory disorders, including but not limited to low blood pressure
!
Skin irritation or pruritus due to medical adhesive (electrodes, tapes, etc.)
!
Infection, inflammation or phlebitis at IV insertion sites or infusion pump infusion set
sites
!
Edema at the insertion site
!
Erythema at the insertion site
!
Allergic reaction
!
Excessive pain or burning sensation associated with injections
!
Headache
!
Vasovagal response or fainting
!
Anemia due to blood sampling
Subject may have an X-ray or ultrasound of the sensor site. X-rays may cause damage to
cells in the body, which in turn may increase the risk of developing cancer. This increase

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in risk associated with each X-ray procedure is extremely low but does slowly increase 
with the increasing number of X-rays tests you have.
Even though there are no known risks of ultrasound imaging, it can produce effects on 
the body. When ultrasound enters the body, it heats the tissues slightly. In some cases, it
can also produce small pockets of gas in body fluids or tissues (cavitation). The long-
term effects of tissue heating, and cavitation are not known.
8.6
POSSIBLE INTERACTIONS WITH CONCOMITANT MEDICAL TREATMENTS
The transmitter is incompatible with magnetic resonance imaging (MRI) procedures. The 
transmitter is MR Unsafe and must be removed before undergoing an MRI procedure. 
Before undergoing an MRI procedure, the subjects should contact the study staff. Subjects 
should also let the MRI staff know that they have a sensor and transmitter. 
The sensor is MR conditional and subjects can be safely scanned in an MR system meeting 
the following conditions:
!
Static magnetic field of 1.5T or 3.0T
!
Maximum spatial field gradient of 2000 gauss/cm (20 T/m)
!
Maximum MR system reported, whole body averaged specific absorption rate (SAR) 
of 4 W/kg (First Level Controlled Operating Mode)
8.7
DEXAMETHASONE
It has not been determined whether the risks usually associated with injectable
dexamethasone apply to the use of dexamethasone elution ring, a highly localized,
controlled-release device.
8.8
ELECTROSTATIC SHOCK
The external device (Transmitter) has been tested and passed the Electrostatic Discharge 
(ESD) test according to IEC 61000-4-2:2008 air and contact immunity test levels in 
accordance with IEC 60601-1-2:2014 EMC collateral standard. No known damage to the
external device or to the overall CGM system has been observed as documented in the 
EMC report.
8.9
EFFORTS TO MINIMIZE RISK
This investigation will be conducted by investigators who are qualified by training and
experienced in the treatment of diabetes mellitus and specifically in the execution of 
hyperglycemia and hypoglycemia challenges. In the event of a clinical emergency,

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detailed safety plans will be in place at each clinical site for monitoring and the 
management of clinically significant hypoglycemia and hyperglycemia. A full resuscitation
cart with defibrillator, and staff trained in the care of diabetes and cardiac emergencies
will be present at site. A nurse, nurse practitioner or physician/PA will be present at the
bedside or unit at all times. A study physician/PA or nurse practitioner will be present
during the hypoglycemia and hyperglycemia challenge times.
In addition, adequate measures including eligibility criteria limitations, subject screening
and pre-visit assessment of the subject’s diabetes status have been incorporated into the 
clinical investigation with the intention of minimizing such risks.
Investigators will be trained in the technique for Sensor insertion and removal.
Investigators will examine the insertion site during each in-clinic visit and document any 
suspected adverse event. Subjects will be instructed to contact the investigator
immediately upon any sign of significant irritation or discomfort or evidence of infection 
as described previously. In addition, an independent medical monitor will review safety
related aspects of the investigation including review of serious adverse events and
unanticipated adverse device effects.
Furthermore, potential risks associated with participation in this investigation will be 
minimized and managed in accordance with 21 CFR Part 812, ISO 1415511, regulations by
local regulatory authorities and requirements of the approving Investigational Review
Boards.
8.10
RISK TO BENEFIT RATIO
The Sponsor believes that any potential risk presented by this investigation has been
minimized and that adequate testing, safeguards, and safety monitoring have been
incorporated into the investigation to further minimize and mitigate the risks.
The Sponsor believes that the value of the knowledge to be gained by conducting this
clinical investigation to demonstrate the safety and accuracy of the Eversense® 180 CGM
System outweighs the potential risks posed to participating subjects.
All potential study Subjects will sign an informed consent form and conduct a discussion
with delegated investigative personnel concerning the risks and benefits of participating
in the clinical trial.
9
ADVERSE EVENTS

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The following are definitions and requirements for adverse event monitoring and
reporting. The definitions and requirements of local regulations will be followed if
different from below.
The name and telephone number of the individual for the Site to contact regarding safety
issues is listed in the General Information and Contacts section in the front of the
protocol. Subjects will contact the Investigator with any questions or concerns. The
Investigator will contact Senseonics with questions regarding recording and reporting of
adverse events.
9.1
ADVERSE EVENT DEFINITIONS
Adverse Event (AE) is defined as any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users 
or other persons, whether or not related to the investigational medical device.  
NOTE 1: This definition includes events related to the investigational medical device 
or the comparator.
NOTE 2: This definition includes events related to the procedures involved.
NOTE 3: For users or other persons, this definition is restricted to events related to 
investigational medical devices.
Serious Adverse Event (SAE) is defined as an adverse event that:
!
Leads to death;
!
Leads to a serious deterioration in the health of the Subject that either:
o
Results in life-threatening illness or injury; or
o
Results in a permanent impairment of a body structure or a body function; or
o
Requires inpatient or prolonged hospitalization; or
o
Results in medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function;
!
Led to fetal distress, fetal death or congenital abnormality or birth defect;
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by 
the CIP, without serious deterioration in health, is not considered a serious adverse 
event.
Anticipated adverse events are AEs that have been identified as possible adverse events 
related to the investigational device or procedure. 

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Unanticipated adverse device effects (UADEs) are defined as any serious adverse effect
on health or safety or any life-threatening problem or death caused by, or associated
with, a device, if that effect, problem, or death was not previously identified in nature,
severity, or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of study subjects.
Severity
Mild: Awareness of a sign or symptom that does not interfere with the Subject’s usual
activity or is transient, resolves without treatment and with no sequelae
Moderate: Interferes with the Subject’s usual activity and/or requires symptomatic
treatment
Severe: Symptom(s) causing severe discomfort and significant impact on the Subject’s
usual activities and/or requires treatment
Causality: The causal relationship should be determined with respect to the investigational
device, the insertion or removal procedure, or other study-related procedures.
None: The event is not associated with the device or procedure. There is no relation
between the event and the device or procedure.
Possibly Related: The temporal sequence between the device or procedure and the event
is such that the relationship is not unlikely or there is no contradicting evidence that can
reasonably explain the Subject’s condition. There is a possibility of any relation between
the event and the device or procedure.
Related: The temporal sequence is relevant, or the event abates upon device application
completion/removal or the event cannot be reasonably explained by the patient’s
condition or comorbidities. The event is related or most likely associated with the device 
or procedure.
Unknown: There is no evidence or relevant data available to assess the relationship
between the event and the device or procedure.
9.2
MONITORING ADVERSE EVENTS
Adverse events (AEs) may be volunteered by Subjects, elicited by Investigator or others, or
observed. All AEs will be assessed by the Investigator who will determine whether or not
the event is related to the device, and/or insertion or removal procedure or other study-
related procedure. The Investigator will determine whether or not the event meets the

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serious criteria. If it is determined that an AE has occurred, the Investigator should obtain
all the information required to complete the reporting process, including source
documentation.
9.3
ADVERSE EVENT REPORTING
All adverse events (AEs) will be reported by the Investigator and reviewed by the Sponsor
in compliance with applicable regulations. Site will follow local IRB reporting
requirements for reporting to IRB.
All SAEs must be reported to Sponsor as soon as possible but in no event later than 3 days
after learning of the event. Include Study ID, Study Site, Adverse Event, causal
relationship to device and procedure (insertion/removal/other study procedure),
seriousness, expectedness, and provide source documentation as soon as available. The
AE form of the CRF must be completed within 3 days of awareness for all SAEs.
All UADEs must be reported to the Sponsor and to the reviewing IRB as soon as possible, 
but in no event later than 3 days after the Investigator first learns of the event. The AE
form of the CRF must be completed as soon as possible but no later than 3 days for all
UADEs.
All adverse events classified as possibly related or related to the device or procedure will
be reported to Senseonics as soon as possible but no later than 3 days of learning of 
events.
9.3.1
AE REPORTING PERIOD
Adverse events are reported from enrollment until study participation has ended.
Adverse events related to the device or procedure will be followed until resolution, AE
has stabilized, or the study has been completed.
9.3.2
PRE-EXISTING MEDICAL CONDITIONS
Pre-existing medical conditions or symptoms reported prior to enrollment will not be
recorded as an AE. In the event there is a change in the pre-existing medical condition or
symptoms due to the device or study-related procedure, then an AE must be recorded.
9.3.3
PROTOCOL SPECIFIC REPORTING INFORMATION
For the purpose of this protocol, mild (i.e., clinically non-significant) hypoglycemia and
hyperglycemia symptoms or blood glucose values out of the normal range will not be
reported as adverse events unless determined to meet the criteria of a Serious Adverse 
Event.

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9.4
DEVICE DEFICIENCIES 
All device deficiencies related to the identity, quality, durability, reliability, safety, or 
performance of an investigational medical device shall be documented throughout the
clinical investigation and appropriately managed by the Sponsor. Device deficiencies 
include malfunctions, use errors, and inadequate labeling.
10 SOURCE DOCUMENTATION, CASE REPORT FORMS AND DATA MANAGEMENT
Data in this study will be collected on Case Report Forms (electronic or paper) as well as
electronic file transfers.
10.1
SOURCE DOCUMENTS AND CASE REPORT FORMS
The investigator or his/her designee at each site is responsible for recording
investigation-related data onto the CRFs and maintain source documentation supporting
the data. Good Clinical Practice in the documentation on source documents and CRFs
will be followed. For source documentation or if papers CRFs are used, the data must be
legibly written in ink. If changes are required, a single line is to be drawn through the
incorrect information, the correct information written in and the change initialed and
dated by the individual making the change. The reason for correction may be noted,
unless obvious. Pencil, correction fluid or correction tape must not be used, and
incorrect information must not be obscured (scribbled-out).
The investigator must review, sign, and date the CRFs as indicated on the form or
electronically; these responsibilities cannot be delegated to another person. It is the
investigator’s responsibility to comply with regulatory requirements including, but not
limited to, the maintenance of accurate, complete and current records relating to the 
CRFs.
The Sponsor (or their designee) will review the data against the original source
documents and ensure any noted discrepancies are resolved by the investigational site.
Subject data will be compared to information originally recorded on source documents
related to the trial (i.e. professional notes, laboratory reports, investigation-specific
worksheets, etc.).
Investigation-related information collected on CRFs will be entered into a secure
database. The database design and installation will be validated prior to use.

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Validation techniques used by Senseonics are consistent with applicable regulations and
guidelines. Each database must pass a series of standard tests that demonstrate the
usability and correctness of the database system to approved specifications. The test
process generates detailed test result logs, which are provided as part of the database
documentation.
The details of data review, database cleaning and data querying are described in a Data 
Quality a n d  Management Plan (DQMP). This plan is updated throughout the 
investigation as amended data management requirements and investigation-specific 
data conventions are determined.
A comprehensive EDC User Guideline will be developed for participating
investigational sites describing general instructions on CRF completion; this
guideline also includes investigation- specific data entry, and query management
instructions.
Data entered by investigational sites will be reviewed by the Sponsor or their
designee on an ongoing basis to ensure adequate query resolution and identify and
query adverse events, protocol deviations, and any other ambiguous data points.
10.2
GLUCOSE MEASUREMENT DATA FLOW PROCESS
10.2.1 TRANSMITTER DATA LOGGING
The Transmitter is a rechargeable, external device worn over the Sensor insertion site
that supplies power to the Sensor. The Transmitter periodically (usually every 5
minutes) reads sensor data and calculates sensor glucose and trends. The information
from the Transmitter is then transmitted for display to a handheld device (e.g.
Smartphone) via Bluetooth Low Energy with AES-CCM encryption. At any one time, the 
Transmitter contains all of the data collected since last erasure, extending back in time
to the limit of its capacity. Each Sensor reading is recorded with a timestamp. Successive 
uploads from a subject’s assigned Transmitter can be assembled into a cumulative time
profile, using these timestamps.
10.2.2 TRANSMITTER DATA RETRIEVAL
Data from Subject Assigned Transmitters will be collected at clinic visits. The data will
be downloaded by a data communication device running Senseonics’ custom software
application and saved to a file. The file will be uploaded to a 21CFR11 compliant record,
utilizing a 21CFR11- compliant third-party software application.

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The Senseonics’ software application will identify the Sensor serial number and ask the 
user to enter the site ID, subject ID and visit number. The file name will include these 
identifiers as well as the download date and time. Transmitter data will also be 
uploaded to a data management system to monitor calibration compliance.  
Incomplete or missing data downloads that cannot be used in the analysis or cannot
be made available at a future visit would be considered missing data for the purpose 
of analysis for the corresponding time interval.
10.2.3 REFERENCE GLUCOSE ANALYZER DATA
Plasma glucose data will be recorded by a YSI Analyzer and recorded on Source 
Document Forms. This data will be transferred to a 21CFR11-compliant electronic
record system. Paper strip records and/or electronic records collected from the YSI
Reference Glucose Analyzer will be retained according to GCP. Printouts should be 
labeled, including a patient identifier, sample number, and operator initials, and either
photocopied or scanned.
10.2.4 BLOOD GLUCOSE METER DATA
Data from the study Subject SMBG Meters will be uploaded at clinic visits and
electronically transferred to a 21CFR11-compliant electronic record system.
Incomplete data downloads that cannot be used in the analysis or cannot be made
available at a future download would be considered missing data for the purpose of 
analysis for the corresponding time interval.
10.2.5 DATA RETENTION
During and/or at the conclusion of the investigation, original data from the laptop at the
clinical site will be transferred to a 21CFR11-compliant electronic record system. The 
clinical site will be provided a master CD/USB of the electronic data to meet record 
retention requirements.
11 STATISTICAL METHODS
11.1
STATISTICAL ANALYSIS OVERVIEW
11.1.1 GENERAL CONSIDERATIONS
The statistical analysis of the data is focused on assessing performance via downloads and 
data from the clinic including the Fingerstick Blood Glucose Meter Data (Subject SMBG), 
the YSI Reference Glucose Data, the Eversense® 180 CGM System Data, and other manual 

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entries (e.g. Implant Time, Subject Number). Descriptive statistics will be used to 
summarize all subject Baseline and outcome data collected during the study.  Continuous 
variables will be summarized using means, standard deviations, and ranges.  Categorical 
variables will be summarized in frequency distributions.
Statistical analyses will be performed by validated software (e.g., MATLAB and SAS® 9.4).  
Adequate source document verification and/or audit activities will be utilized to assess 
the validity of investigation conclusions.  Copies of databases used to prepare clinical 
report summaries will be archived to enable any statistical analyses performed to be 
replicated.
11.1.2 DATA POOLING 
Subjects will be selected consecutively (i.e., selecting every subject in the order they 
present at the site) among those who meet the inclusion/exclusion criteria.  All subjects 
will receive sensors and transmitters.  The primary effectiveness measure (MARD) will 
be analyzed with data pooling across sites.  Site effects will be examined, but only 
descriptively.
Analyses will be performed based on aggregating all patients in the study, and again 
separately for each randomized groups. The analysis by randomized groups will be only 
performed descriptively and there will be no formal statistical comparisons. Transmitters 
will be designated as primary (left arm) and secondary (right arm).
Analyses will be performed for subgroup of interest (based on type of diabetes (type I vs. 
type 2), age (≥ 65 years of age vs. < 65), and baseline HbA1c (≥8% vs. < 8%).
11.1.3 SENSOR EVALUATION PERIOD
The Eversense® 180 CGM System performance will be evaluated in the period after 
insertion.  The Transmitter will assess the Sensor’s signal sensitivity in real time for any 
premature failure independent of the expected lifetime based on time from insertion.  If 
the measurement of potential degraded response of the Sensor optical system signal 
drops below a pre-defined percent of its original value and/or systemic patterns in Sensor 
accuracy to entered calibration points drops below a pre-defined threshold, then the 
device has reached it end of life (sensor retirement) and will no longer provide glucose 
readings.  This end of life determination marks the end of the accuracy evaluation period 
for this Sensor.  The distribution of times between Sensor insertion and end of life or 
completion of scheduled study visits, whichever occurs first will be summarized.

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11.1.4 EXPECTED PAIRED POINTS BY RANGE*
The expected number of paired YSI/sensor points by YSI glucose range are targeted as 
follows:
Day  
1
Day   
7
Day 
14
Day 
22
Day 
30
Day 60 Day 
90
Day 
120
Day 
150
Day 
180
Total 
through 
180 days
YSI Range / 
Min # of 
subjects
160
80
80
160 160
160
155
140
130
112-
120
40-70     
mg/dL
104
0
520
520
104
0
104
0
1040
100
8
910
845
728-
780
8691-8743
71-299   
mg/dL
440
0
2200 2200 440
0
440
0
4400
426
3
3850
3575
3976-
4260
37664-
37948
300-400 
mg/dL
128
0
640
640
128
0
128
0
1280
124
0
1120
1040
896-
960
10696-
10760
Total
672
0
3360 3360 672
0
672
0
6720
651
0
5880
5460
5600-
6000
57050-
57450
Total paired 
points
57050-
57450
*Estimates based on 160 subjects inserted, with challenge type distributed equally  
11.1.5 EVALUABLE DATA FOR ANALYSIS
All data will be evaluable for the study safety and effectiveness analysis.
11.1.6 ANALYSIS POPULATION
Effectiveness Analysis population: The effectiveness analysis and exploratory 
effectiveness endpoints will be based on all data from all subjects in this investigation 
with at least one paired glucose reading (one Sensor with one reference glucose). The 
Eversense® 180 CGM System and reference readings are compared by pairing each 
reference reading with the first Sensor reading that occurred up to 5 minutes after 
sample acquisition.  
Safety Analysis Population: Safety analysis will be based on all subjects that undergo the 
sensor insertion in this investigation.

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11.1.7 SUBJECT ACCOUNTABILITY 
A Subject Accountability flow diagram will account for all subjects from informed consent 
through end of study and includes any early explants or withdrawals (Figure 1 in 
APPENDIX 1).  
11.1.8 STUDY DEMOGRAPHICS ANALYSIS
Descriptive statistics will be provided for demographic variables and other baseline 
characteristics, such as age, gender, race, BMI, diabetes type, insulin therapy, history of 
ketoacidosis, and history of hypoglycemia.  
11.1.9 TABULATION OF INVESTIGATIONAL DEVICE DEFICIENCIES
11.1.9.1 TRANSMITTER DEFICIENCIES
A tabulation of all reported transmitter device deficiencies will be presented (Table 1 in 
APPENDIX 1).
11.1.9.2 SENSOR DEFICIENCIES
A tabulation of all reported sensor device deficiencies will be presented (Table 2 in 
APPENDIX 1).
11.2
SAFETY ENDPOINTS
The safety endpoint is the incidence of device-related or insertion/removal procedure-
related serious adverse events (SAEs) in the clinic and during home use through 180 days 
post-insertion. 
An Adverse Event is considered ‘related’ if the relatedness is categorized as ‘possibly 
related’, or ‘related’. The assessment of seriousness and relatedness made by the Medical 
Monitor will be used for analysis.  The numbers of SAEs and the percentage of patients 
with SAEs will be reported for each SAE type that is observed, identified as device-related, 
procedure-related or unrelated to the study (Table 3 in APPENDIX 1).   The count and 
proportion of patients experiencing at least one device-related or procedure-related SAE 
will be presented. No inferential statistical analysis will be performed.
Other safety endpoints include:
!
Incidence of insertion/removal procedure or device-related adverse events in the 
clinic and during home use.
!
Incidence of all adverse events in the clinic and during home use.
!
Incidence of hospitalizations due to hypoglycemia, hyperglycemia or ketoacidosis 
occurring during home use.

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!
Incidence of reported hypoglycemic and hyperglycemic events occurring during 
home use.
For each of the adverse event (AE or SAE) categories above, the numbers of AEs and the 
percentage of patients with AEs will be reported for each AE type that is observed and be 
stratified by the target age enrollment categories (Tables 4A-4E in APPENDIX 1).   A listing 
(Table 5 in APPENDIX 1) will be prepared that identifies each patient with a reported AE or 
SAE, and relevant information including date of onset, severity level, seriousness, 
relatedness to the device or procedure, classification as anticipated or unanticipated, 
corrective action(s) taken, and resolution status (resolved or ongoing).
11.3
EFFECTIVENESS ENDPOINTS
11.3.1 SUMMARY
The effectiveness measure will be the mean absolute relative difference (MARD), 
calculated for all paired Sensor and reference measurements through 180 days post-
insertion.  
11.3.2 EFFECTIVENESS MEASURE
11.3.2.1 EFFECTIVENESS MEASURE: CRITERIA
The effectiveness objective is to descriptively document the distribution of absolute 
relative difference across all evaluable subjects and to estimate the MARD. MARD will be 
calculated based on all the data through 180 days of Sensor use.   Descriptive statistics 
will be provided for the MARD.  There is no hypothesis to be tested.  No inferential 
statistical analysis will be performed.
The effectiveness measure is the mean absolute relative difference (MARD), defined as 
the average of absolute difference of paired Eversense® 180 CGM System and reference 
glucose readings divided by the reference glucose reading (reference) for all reference 
glucose values, that is:  
MARD = 		∑| () –() |
()

n
⁄
 × 100%,
Where, n is the total number of CGM and reference glucose pairs during the evaluation 
period, that is, through 180 days of Sensor use.

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11.3.2.2 SAMPLE SIZE AND POWER CACULATION
This study does not feature any inferential statistics.  The sample size for the study was 
not determined based on a power calculation but was based on the desire to obtain a 
minimum number subjects at the 180 day visit (i.e. 120) 
Additionally, the enrollment target of 20 patients per subgroup of interest (based on 
type of diabetes (type I vs. type 2), age (≥ 65 years of age vs. < 65), and baseline HbA1c
(≥8% vs. < 8%) will provide a clinically reasonable amount of data to characterize these 
subgroups. A subgroup of size 20 will provide an 80% probability of observing one or 
more rare events in that subgroup for a subgroup population rate as low as 8%.  
11.3.2.3 OTHER EXPLORATORY EFFECTIVENESS MEASURES
Other exploratory effectiveness measures are discussed in this section.  Only 
descriptive statistics will be provided for these exploratory outcomes.  
11.3.2.3.1
MEAN ABSOLUTE DIFFERENCE (MAD) BETWEEN SENSOR AND REFERENCE 
MEASUREMENTS 
MAD =
	$ | (Glucose),-.,/0 – (Glucose)0-1-0-.2- |
n
3
11.3.2.3.2
MEAN RELATIVE DIFFERENCE (RD) BETWEEN SENSOR AND REFERENCE 
MEASUREMENTS 
Mean RD = 55$ (Glucose),-.,/0 – (Glucose)0-1-0-.2-
(Glucose)0-1-0-.2-
6
n
3
6 × 100%
11.3.2.3.3
MEDIAN ABSOLUTE RELATIVE DIFFERENCE (ARD) BETWEEN SENSOR AND 
REFERENCE MEASUREMENTS 
Median ARD = Median ((
| () –() |
()
)i) x 100%, i = 1, 2, …, n
11.3.2.3.4
MEDIAN ABSLOUTE DIFFERENCE BETWEEN SENSOR AND REFERENCE 
MEASUREMENTS
Median AD = Median ( | (Glucose),-.,/0 – (Glucose)0-1-0-.2- |9), i = 1,2, … , n
11.3.2.3.5
MEDIAN RELATIVE DIFFERENCE BETWEEN SENSOR AND REFERENCE 
MEASUREMENTS
Median RD = Median ((
() –()
()
)=) × 100%, i = 1, 2, …, n

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11.3.2.3.6 SYSTEM AGREEMENT WITH REFERENCE
The Agreement of the CGM System to reference measurements will be assessed by 
looking at the differences (
|() –() |
()
) x 100% in intervals of [0 
– 15%], [0 – 20%], [0-30%], and [0-40%). For readings less than or equal to 80 mg/dL, the 
absolute difference in mg/dL between the two glucose results will be calculated. For 
values greater than 80 mg/dL, the absolute percent difference (%) from the reference 
values will be calculated. 
11.3.2.4 EFFECTIVENESS MEASURE IN FULL GLUCOSE RANGE AND DIFFERENT GLYCEMIC 
REGIONS
Mean/median absolute relative difference, mean/median relative difference, 
mean/median absolute different when reference YSI≤70 mg/dl, and Agreement between 
CGM and YSI glucose will be stratified based on YSI glucose ranges. Similar stratification 
based on CGM glucose will also be performed. (Tables 6A-6D in APPENDIX 1).
11.3.2.5 CONCURRENCE OF SYSTEM READINGS AND YSI VALUES
Tables for concurrence of system and YSI values will be tabulated (Tables 7A and 7B in 
APPENDIX 1). 
11.3.2.6 STABILITY OF THE SYSTEM THROUGHOUT SENSOR LIFE
For the full 180 day duration of the study, performance of the system overtime will be 
assessed by visit number (Table 8 in APPENDIX 1).  
11.3.2.7
SENSOR PRECISION ANALYSIS
Sensor precision will be evaluated by paired absolute relative difference (PARD) and 
percent coefficient of variation (PCV). PARD is the absolute value of the Primary Sensor 
reading minus the paired Secondary Sensor reading divided by the average of the two 
Sensor readings. PCV is the standard deviation of the two paired Sensor readings 
divided by the average of the two paired Sensor readings. The mean values of PARD and 
PCV will be tabulated (Table 10 in APPENDIX 2).
PARD = 55$ ∀Glucose),-.,/0 ? – (Glucose),-.,/0 @ ∀
( Mean Glucose),-.,/0 ? ABC @
6
n
3
6 × 100%
PCV = 		∑,F G () H ABC () I
( JAB ) H KLM I

n
⁄
 × 100%

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11.3.2.8 CALIBRATION FREQUENCY ANALYSIS
After the conduct of the study, additional effectiveness analyses will be performed with 
a modified calibration scheme to support 1 calibration per day after Day 21 following 
Sensor insertion (i.e., calibration will be performed twice (2) per day for Days 1-21, 
followed by once (1) per day for Days 22 until the end of Sensor life).  It is important to 
note that the raw clinical data that is collected by the Sensor is independent of the 
calibration values that are entered into the MMA. Performing the effectiveness analyses 
after the collection of Sensor data is analogous to how the effectiveness analyses were 
performed to demonstrate the accuracy of the algorithm change that was included in 
Software 602 (SW602), which was approved in the Eversense CGM System PMA 
(P160048). A separate statistical analysis plan will be developed for this analysis to 
evaluate the new calibration frequency.
12 DEVICEACCOUNTABILITY
Only an approved Investigator and investigational site may receive and use the Eversense®
180 CGM System. The product will be packaged and labeled to clearly indicate that it is for
clinical investigational use only, and the investigational device must only be used in
subjects enrolled in this investigation. The Investigator is responsible for investigational
product accountability, reconciliation, and record maintenance. The accountability
includes storage of the investigational supplies in a secured location according to the
conditions set forth for the device on the label. The investigator must maintain
investigational product accountability records throughout the course of the investigation
including receipt, use, and final disposition of investigational inventory. The accountability 
includes documenting the part number, lot number, serial number (and expiration date for
sterile components) of investigational device (as applicable) assigned to each subject.
All investigational product (used or not used) must be returned to Senseonics unless
otherwise instructed by Senseonics. Explanted Sensors will also be returned to Senseonics
using Biohazard Return instructions and supplies.
13 ETHICAL AND REGULATORY CONSIDERATIONS
13.1
STATEMENT OF COMPLIANCE AND GOOD CLINICAL PRACTICE
This clinical investigation will be conducted in compliance with the principles that have 
their origin in the Declaration of Helsinki (Revision 6, 2008), this clinical investigation plan,
requirements of the approving IRB or EC, US Code of Federal Regulations applicable to

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clinical studies, ICH GCP E6, ISO 14155 and other applicable regulatory requirements.
This clinical investigation will not be initiated until approval has been obtained from the
FDA or local regulating authority as well as IRB/ EC. No deviation from the protocol will be
implemented without the prior review and approval of the Sponsor and /or IRB except
where it may be necessary to eliminate an immediate hazard to a subject. In such case, the
deviation will be reported to the IRB and Sponsor per their reporting requirements.
13.2
INFORMED CONSENT AND INVESTIGATIONAL REVIEW BOARD
The Investigator is responsible for assuring that informed consent is obtained from each
subject or (legally authorized representative) prior to participation in the clinical
investigation, according to the local clinical site’s IRB and applicable regulatory
requirements.
The Investigator will prepare an informed consent form (ICF) in accordance with this
protocol and applicable regulatory requirements. Prior to the start of the study or
revision to study, the informed consent form will be reviewed by the Sponsor for
consistency with protocol, and then must be submitted to and approved by the IRB. A
copy of the final IRB approved consent form and notification of approval of the clinical
protocol must be received and approved by the Sponsor prior to start of study or 
revision to study. Timely approvals for the continuation of the trial as well as the
informed consent form at each clinical site must also be forwarded to the Sponsor.
While an Investigator may discuss general availability of the investigation with a
prospective subject without first obtaining consent, informed consent must be obtained
from a subject prior to initiation of any clinical procedures dictated by the protocol (e.g.,
pregnancy testing) that are performed solely for the purpose of determining eligibility
to participate in the clinical investigation.
The informed consent process includes both verbal and written explanation. Subjects
must be fully counseled and informed of their options, risks and benefits, and have every 
opportunity to ask questions about participation in the investigation. Insurance
coverage will be explained to the subject. This process includes a thorough explanation
of the informed consent document that the subject will be asked to sign acknowledging
that they understand and desire to participate in the investigation. The subject will be
provided a copy of the signed informed consent form. The original ICF remains at the 
investigational site.

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If new information regarding the investigational device becomes available and/or the
protocol changes and this information can significantly affect a subject’s future health
and medical care, subjects will be informed of the information and may be asked to sign
a revised informed consent form.
The Investigator will notify the Sponsor within 5 working days, a withdrawal of approval 
by the reviewing IRB of the investigator’s part of an investigation. 
13.3
PAYMENT FOR PARTICIPANTS
Subjects will be compensated for their time and travel expenses as detailed in the 
Informed Consent document.
13.4
AMENDMENTS TO THE PROTOCOL
Investigators may not modify this protocol without obtaining written concurrence of the 
sponsor and approval by the IRB and required regulatory authorities.
13.5
SPONSOR RESPONSIBILITIES 
As the Sponsor of this clinical trial, Senseonics Incorporated has the overall responsibility
for the conduct of the clinical trial, including assurance that the study meets the
regulatory requirements of the appropriate regulatory bodies. In this study, the Sponsor
will have certain direct responsibilities and may delegate other responsibilities to
another organization such as a Contract Research Organization (CRO).
The Sponsor will submit all reports required by the appropriate regulatory authorities,
including unanticipated adverse device effects, withdrawal of IRB approval, current
investigators list, annual progress reports, final report, and protocol violations.
The Sponsor will select the qualified Investigators who will conduct clinical investigations
of medical devices under 21 CFR Part 812 and applicable local and regulations.
The Sponsor will maintain copies of correspondence, all data, device shipment records,
adverse events, device accountability, and required study documentation as required by
the appropriate regulatory authorities.
13.6
INVESTIGATOR REPONSIBILITIES AND DELEGATION OF STUDY SPECIFIC TASKS
The Investigators commit themselves to conducting the investigation in accordance with
the Clinical Trial Agreement, Protocol, and applicable FDA and local regulations for
patient safety and control of investigational devices. Investigators are responsible for

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submitting and obtaining initial and continuing review of the clinical trial at least
annually unless otherwise directed by the IRB and completing all required reports.
Study-specific tasks may be delegated by an Investigator to individuals who are qualified
by education, training, and experience. However, the Principal Investigator remains
responsible for the conduct of the clinical trial.
A Delegation of Authority Log will be maintained to document the study personnel and
their roles and delegated tasks. No study-specific tasks may be performed prior to the
appropriate training and completion of the Delegation of Authority Log.
Records to be maintained by the Investigator include, but are not limited to: clinical trial
investigational plan and all amendments, signed clinical study agreement, signed financial
disclosure forms, IRB communication including approvals and informed consent forms,
IRB membership list, correspondence related to the trial, curriculum vitae, delegation of 
authority documentation, sponsor sign-in documentation, laboratory certification and
normal ranges, reports (including annual reports, final reports). For each subject
enrolled: signed informed consent form(s), all completed case report forms with source
documentation supporting the data, and supporting documentation related to any
complication or adverse event.
13.7
TRAINING
The Sponsor or designee will provide training to the investigator(s) and site personnel.
Training will occur before the first device use and/or protocol-specific task. To ensure
protocol and regulatory compliance as well as accurate data collection, site training will
include a detailed review of the protocol, device accountability, CRF completion,
investigation-specific procedures, monitoring logistics, and regulatory requirements. The
appropriate investigator(s) and site personnel will be trained on procedures for insertion
and removal of the Sensor by qualified personnel (e.g. trained investigators and
investigative staff, Sponsor personnel) using appropriate training materials (e.g.
investigator meetings, demonstrations, labs, webinars, etc.). Only the personnel
responsible for the insertion and removal of the sensor will be required training on the
insertion/removal procedures.
Documentation of site personnel qualification and training will be maintained in the site’s
clinical files and Sponsor files. Training will be updated as appropriate, for example for
protocol amendments, revisions, and any device changes.
13.8
PROTOCOL COMPLIANCE

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Senseonics will evaluate protocol deviations and Subject compliance during the
investigation. Individual event corrective and preventive actions may be recommended.
Deviations occurring across investigational sites will be reviewed by Senseonics on an 
ongoing basis to determine if more global preventive actions may be required.
13.9
PROTOCOL DEVIATION
Ongoing monitoring of protocol compliance will be performed for each site. The sponsor
has the right to suspend enrollment at sites deemed to have excessive protocol
compliance issues.
The investigator agrees to conduct the investigation in accordance with this protocol. An
investigator must not intentionally deviate from the protocol without prior approval from
the Sponsor, except when necessary to eliminate apparent immediate hazards to a 
subject, or when the changes(s) involves logistical or administrative aspects of the study 
and do not affect the subject’s rights, safety and well-being, or the scientific integrity of 
the study.
Protocol deviations are documented on CRFs. Investigators will also adhere to
procedures for reporting investigation deviations to the IRB in accordance with the
specific IRB reporting policies and procedures.
Under emergency circumstances, deviations from this protocol to protect the rights, 
safety and well-being of a subject may proceed without prior approval of the Sponsor and 
the IRB. Such deviations must be reported to the Sponsor within 48 hours of occurrence 
and respective regulatory bodies as soon as possible per applicable reporting 
requirements.
13.10 DOCUMENT STORAGE AND RETENTION
All study records will be maintained according to local regulatory requirements or for two
years after marketing approval is obtained or two years after the site is notified that this
research protocol has been terminated by the Sponsor. Record retention dates will be
provided to all parties concerned by the Sponsor. Following the end of the retention
period, all records may be destroyed (papers shredded or deleted from electronic
media).
It is the investigator’s responsibility to meet applicable local retention requirements for
all investigation-related records and the investigator must notify Senseonics prior to
discarding any of these records.

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13.11 CONFIDENTIALITY OF DATA
All information and data pertaining to the clinical trial will be considered confidential.
Only authorized personnel may have access to the confidential data. Authorized
personnel from the regulatory authorities have the right to inspect and copy all records
pertinent to this trial. All data used in the analysis and reporting of this evaluation will
be without identifiable reference to the Subject.
13.12 CLINICAL STUDY MONITORING
The Sponsor or its designee will conduct investigational site monitoring visits to ensure
compliance with the protocol and the Investigator Agreement.
Monitoring will be carried out in compliance with 21 CFR Part 812, ISO 14155, Good
Clinical Practice (GCP) Guidelines, regulatory requirements, written standard operating
procedures, and an investigation-specific Monitoring Plan. The Monitoring Plan will
specify the minimum frequency, scope, and general conduct of monitoring visits as well
as identify any relevant study-specific monitoring responsibilities.
The monitoring responsibilities may be delegated by the Sponsor to a Clinical Research
Organization (CRO). Monitors for this study must be qualified by education, experience,
and training. The qualifications of monitors will be kept on file.
The investigator or their designee will permit access to subject source documents and
study documentation in order to verify that information on case report forms (CRFs) is
accurate and complete and study documentation is up to date and complete.
13.13 MEDICAL MONITOR
A Medical Monitor will be appointed to provide safety oversight for the investigation. The 
appointed Medical Monitor will be an independent physician with relevant therapeutic 
and medical expertise that is not participating as a clinical investigator in the clinical trial 
and does not have a financial, scientific, or other conflict of interest with the clinical trial.
Specific responsibilities of the Medical Monitor will include the following:
•
Provide medical and scientific input to review applicable clinical data, subject medical 
safety data and laboratory values
•
Maintain ongoing assessment of the safety profile of the investigational device during 
the investigation
•
Provide medical surveillance and evaluation of all device or procedure related adverse 
events, including serious adverse events (SAEs) and unanticipated adverse device 
effects (UADEs) on a periodic basis 

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!
Ensure implementation of the study stopping rule(s)
•
Adverse event adjudication including:
o
Assess and assign device and procedure relatedness used in the safety 
endpoint analysis
o
Provide adverse event categorization and physiologic system assignment
o
Provide adverse event characterization for Severity and if anticipated or 
unanticipated 
•
Other safety management/oversight as called upon by Senseonics during the study
In addition to engagement in individual adverse event adjudication, the Medical Monitor 
will complete a safety data review of summary data across all sites to include:
•
Adverse event summaries
•
Adverse event endpoint review
•
Unanticipated adverse device effects review 
•
Summary of protocol deviations, device deficiencies, subject terminations, and 
subject withdrawals related to device or procedure safety 
•
Study stopping rule assessment
Safety data review procedures will comply with the Safety Management Plan, which will 
include processes for individual event review and adjudication, periodic   safety data 
review and safety surveillance, and adverse event reporting requirements. Safety data 
review minutes will be documented in the study file.
13.14 AUDITING
The Sponsor or designee may perform periodic site and study file audits to evaluate
compliance with standards and Good Clinical Practice. Audits may include, but are not
limited to, device supply, presence of required documents, the informed consent
process, and comparison of CRFs with source documents. The investigator agrees to
participate with audits conducted at a reasonable time, in a reasonable manner.
13.15 INSURANCE AND INDEMNITY
Clinical trial insurance will be secured prior to investigation initiation.
14 FINAL REPORT

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Upon completion or termination of the study, the PI must submit a final written report to
the Sponsor and IRB as required by the regulations. The report should be submitted within
approximately 3 months (90 days) of completion or termination of the trial.
The Sponsor will submit a final report as required by the appropriate regulatory authorities.
15 PUBLICATIONPOLICY
Publication by Senseonics
Senseonics may at any time publish the results of and information pertaining to the
investigation Subject only to ensure compliance with regulatory requirements pertaining
to subject protected health information.
Publication by the Investigational Sites
Investigators will be invited to publish the results of this clinical investigation. The 
conditions under which an investigator may publish results from this clinical investigation
in any form are defined in detail in the clinical trial agreement.

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16 REFERENCES
1.
Rewers M, Pihoker C, Donaghue K, Hanas R, Swift P, Klingensmith GJ. Assessment and
monitoring of glycemic control in children and adolescents with diabetes. Pediatr
Diabetes. 2009 Sep;10 Suppl 12:71-81.
2.
Weinstein RL, Schwartz SL, Brazg RL, Bugler JR, Peyser TA, McGarraugh GV. Accuracy
of the 5- day FreeStyle Navigator Continuous Glucose Monitoring System: comparison
with
frequent
laboratory
reference
measurements.
Diabetes
Care.
2007 
May;30(5):1125-30.
3.
Zisser HC, Bailey TS, Schwartz S, Ratner RE, Wise J. Accuracy of the SEVEN continuous
glucose
monitoring system: comparison with frequently sampled venous glucose
measurements. J Diabetes Sci Technol. 2009 Sep 1;3(5):1146-54.
4.
Garg S, Zisser H, Schwartz S, Bailey T, Kaplan R, Ellis S, Jovanovic L. Improvement in
glycemic
excursions with a transcutaneous, real-time continuous glucose Sensor: a 
randomized controlled trial. Diabetes Care. 2006 Jan;29(1):44-50.
5.
Clinical and Laboratory Standards Institute. Performance Metrics for Continuous
Interstitial Glucose Monitoring: Approved Guideline. CLSI Document POCT05-A.
Wayne, PA. 2008.
6.
In-vitro Diagnostic Test Systems-Requirements for Blood Glucose Monitoring Systems
for Self Testing in Managing Diabetes Mellitus. ISO 15197:2003. Geneva.
7.
U.S.
Food
and
Drug
Administration.
Content
of
Premarket
Submissions
for
Management of Cybersecurity in Medical Devices. Guidance. 2014
8.
U.S. Food and Drug Administration. The Content of Investigational Device Exemption
(IDE) and
Premarket Approval (PMA) Applications for Artificial Pancreas Device
Systems. Draft Guidance. 2011.
9.
U.S. Food and Drug Administration. Design Considerations for Pivotal Clinical
Investigations for Medical Devices. 2013.
10. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group: 
Effectiveness of continuous glucose monitoring in a clinical care environment: evidence 
from the Juvenile Diabetes Research Foundation continuous glucose monitoring (JDRF-
CGM) trial. Diabetes Care 2010;33:17-22.
11. Clinical investigation of medical devices for human subjects — Good clinical
practice. ISO 14155:2011. Geneva.
12. CLSI. Performance Metrics for Continuous Interstitial Glucose Monitoring; 
Approved Guideline. CLSI document POCT05-A. Wayne, PA: Clinical and 
Laboratory Standards Institute; 2008.
13. Deiss D, Szadkowska A, Gordon D et al. Clinical practice recommendations on 
the routine use of Eversense, the first long-term implantable continuous 
glucose monitoring system. Diabetes Technol Ther 2019;21 
DOI:10.1089/dia.2018.0397
14. Deiss D, Irace C, Carlson G et al.  Real-World Safety of an Implantable 
Continuous Glucose Sensor over Multiple Cycles of Use: A Post-Market Registry 
Study. Diabetes Technol Ther. DOI: 10.1089/dia.2019.0159

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15.Tweden KS, Deiss D, Rastogi R et al. Longitudinal analysis of real-world performance 
of an implantable continuous glucose sensor over multiple sensor insertion and 
removal cycles. Diabetes Technol Ther 2019; DOI:10.1089/dia.2019.0342

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17 APPENDIX 1 EXAMPLE FIGURES AND TABLES OF STATISTICAL ANALYSIS RESULTS
Figure 1. Subject Accountability (Sample Data)
109 subjects consented
13 subjects (01-001, 04-002, 05-001, 06-001, 05-012, 04-011, 02-007, 02-008, 07-
002, 07-006, 05-021, 07-008, and 07-009) had screen failure
15 subjects (01-005, 01-006, 01-007, 01-009, 01-010, 01-012, 01-013, 01-014, 04-
003, 04-004, 05-003, 03-002, 05-015, 02-011, and 07-003) withdrew consent due 
to exceeding screening window
81 subjects completed sensor insertion
10 subjects (02-001, 03-001, 04-001, 05-002, 06-004, 01-002, 01-003, 01-004, 01-
008, and 01-011) are the training subjects
71 subjects are included in the effectiveness and safety endpoints
71 subjects completed Day 30 Visit
2 subject (01-017 and 04-009) withdrew consent
1 subject (03-010) withdrew consent due to AE
68 subjects completed Day 90 Visit
2 subjects (04-008 and 06-017) completed study with sensor retirement alert
66 subjects completed Day 180 Visit  
Table 1. Investigational Transmitter Deficiencies (Sample Data)
Type of Transmitter Deficiency
Number Reported
% of Total
Package Label
0
0%
Product Defect
21
87.5%
Damaged Package
0
0%
Product Safety
0
0%
Product Performance
1
4.2%
Other
2
8.3%
Table 2. Investigational Sensor Deficiencies (Sample Data)
Type of Sensor Deficiency
Number Reported
% of Total
Package Label
0
0%
Product Defect
21
87.5%
Broken Sterile Seal
0
0%
Damaged Package
0
0%
Product Safety
0
0%
Product Performance
1
4.2%

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Other
2
8.3%
Table 3. Summary of Serious Adverse Events (Sample Data) 
SAEs by 
Relationship to 
Study
Number 
of SAEs
Number of 
Patients with 
SAEs (%; 95% 
Confidence 
Interval)
All SAEs
1
1 (1.4%; 0.0%-
7.6%)
Device Related 
SAEs
0
0 (0.0%; 0.0%-
5.1%)
Sensor 
Insertion/Removal 
Procedure Related 
SAEs
0
0 (0.0%; 0.0%-
5.1%)
Unrelated to 
Study SAEs
1
1 (1.4%; 0.0%-
7.6%)
Table 4A. Other Safety Endpoint (Sample Data)
Type of Incidence
Number 
of 
Incidents
Number (%) of 
Subjects with 
Incidents
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor 
0
0 (0.0%)
Incidence of insertion/removal procedure or 
device-related adverse events in the clinic and 
during home use
12
11 (15.5%)
Incidence of all adverse events in the clinic and 
during home use
35
24 (26.6%)
Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use
0
0 (0.0%)
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use
2
2 (2.8%

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Table 4B. Other Safety Endpoint for Subjects between 18 and 20 Years Old (Sample Data)
Type of Incidence
Number 
of 
Incidents
Number (%) of 
Subjects with 
Incidents
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor 
0
0 (0.0%)
Incidence of insertion/removal procedure or 
device-related adverse events in the clinic and 
during home use
12
11 (15.5%)
Incidence of all adverse events in the clinic and 
during home use
35
24 (26.6%)
Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use
0
0 (0.0%)
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use
2
2 (2.8%
Table 4C. Safety Endpoint for Subjects between 21 and 44 Years Old (Sample Data)
Type of Incidence
Number 
of 
Incidents
Number (%) of 
Subjects with 
Incidents
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor 
0
0 (0.0%)
Incidence of insertion/removal procedure or 
device-related adverse events in the clinic and 
during home use
12
11 (15.5%)
Incidence of all adverse events in the clinic and 
during home use
35
24 (26.6%)

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Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use
0
0 (0.0%)
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use
2
2 (2.8%
Table 4D. Safety Endpoint for Subjects between 45 and 65 Years Old (Sample Data)
Type of Incidence
Number of 
Incidents
Number (%) of 
Subjects with 
Incidents
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor 
0
0 (0.0%)
Incidence of insertion/removal procedure or 
device-related adverse events in the clinic and 
during home use
12
11 (15.5%)
Incidence of all adverse events in the clinic and 
during home use
35
24 (26.6%)
Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use
0
0 (0.0%)
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use
2
2 (2.8%
Table 4E. Safety Endpoint for Subjects over 65 Years Old (Sample Data)
Type of Incidence
Number of 
Incidents
Number (%) of 
Subjects with 
Incidents
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor 
0
0 (0.0%)
Incidence of insertion/removal procedure or 
12
11 (15.5%)

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device-related adverse events in the clinic and 
during home use
Incidence of all adverse events in the clinic and 
during home use
35
24 (26.6%)
Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use
0
0 (0.0%)
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use
2
2 (2.8%
Table 5. Full List of Adverse Events (Sample Data)
Descriptions
ID
AE Description
1
1-
16
Depressive period
2
1-
22
Hypoglycaemic episode during the night, patient had to be assisted to drink glucose to regain full conciousness.
3
1-
22
Reduced vision due to ocular ischaemia
4
1-
23
Contact dermatitis at the precise location of the transmittersticker. left arm - Dermatitis has healed
5
2-
02
Cold and runny nose - allergies? ?hayfever
Characteristics
ID
AE 
Category
AE Physiologic 
System
Implant 
Date
Date 
AE 
Onset
Resolution 
Date
Status
Seriousness
Severity
Device 
Related
Procedure 
Implant/Removal 
Related
1
1-16
Psychologic
al disorder
Other
04-DEC-
2014
22-
DEC-
2014
31-DEC-
2014
Resolved
Not SAE
Moderate
Possibly 
Related
Not Related
2
1-22
Hypoglycem
ic Event
Endocrine
20-JAN-
2015
29-
JAN-
2015
29-JAN-
2015
Resolved
Not SAE
Moderate
Not 
Related
Not Related

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3
1-22
Ocular 
ischemia
HEENT
20-JAN-
2015
24-
DEC-
2014
.
Ongoing
Not SAE
Moderate
Not 
Related
Not Related
4
1-23
Dermatitis
Dermatological
20-JAN-
2015
28-
FEB-
2015
18-MAR-
2015
Resolved
Not SAE
Moderate
Definitely 
Related
Not Related
5
2-02
Allergy -
Seasonal
HEENT
19-JAN-
2015
01-
FEB-
2015
16-FEB-
2015
Resolved
Not SAE
Mild
Not 
Related
Not Related
Table 6A.  CGM System Difference to YSI within YSI Glucose Range (Sample Table)
YSI Glucose 
Ranges 
(mg/dL)
Number of 
Paired CGM-
YSI
Mean Relative 
Difference (%)
Median 
Relative 
Difference (%)
Mean Absolute 
Relative 
Difference (%)
Median Absolute 
Relative 
Difference (%)
Overall
<40*
40-60*
61-80*
81-180
181-300
301-350
351-400
>400
*For YSI ≤80 mg/dl, the differences in mg/dl are included instead of percent difference (%).
Table 6B.  CGM System Difference to YSI within CGM System Glucose Range (Sample Table)
CGM System 
Glucose 
Ranges 
(mg/dL)
Number of 
Paired CGM-
YSI
Mean Relative 
Difference (%)
Median 
Relative 
Difference (%)
Mean Absolute 
Relative 
Difference (%)
Median Absolute 
Relative 
Difference (%)
Overall
40-60*
61-80*
81-180
181-300
301-350
351-400
*For CGM ≤ 80 mg/dL, the differences in mg/dL are included instead of percent difference (%).
Table 6C.  CGM System Agreement to Reference within YSI Glucose Ranges (Sample Table)

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YSI Glucose
Range (mg/dL)
Number of Paired
Eversense® CGM
and YSI Reference
Percent of CGM System Readings Within
Percent
15/15% of
Reference
Percent
20/20% of
Reference
Percent
30/30% of
Reference
Percent
40/40% of
Reference
Percent
Greater 
than
40/40% of
Reference
Overall
< 40
40 - 60
61 - 80
81 - 180
181 - 300
301 - 350
351 - 400
> 400
Table 6D.  CGM System Agreement to Reference within CGM System Glucose Ranges (Sample 
Table)
CGM System 
Glucose
Range (mg/dL)
Number of Paired
Eversense® CGM
and YSI Reference
Percent of CGM System Readings Within
Percent
15/15% of
Reference
Percent
20/20% of
Reference
Percent
30/30% of
Reference
Percent
40/40% of
Reference
Percent
Greater 
than
40/40% of
Reference
Overall
40 - 60
61 - 80
81 - 180
181 - 300
301 - 350
351 - 400
Table 7A.  Concurrence of CGM System Readings and YSI Values within YSI Glucose Ranges 
(Sample Table)
YSI
(mg/dL)
Number of 
Paired
CGM-YSI 
(n)
Percent of Matched Pairs in Each CGM System Glucose Range for Each YSI Glucose 
Range 
CGM (mg/dL)
40-60
61-80
81-120
121-160 161-200 201-250 251-300 301-350 351-400
<40
40-60
61-80
81-120
121-160
161-200
201-250
251-300
301-350

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YSI
(mg/dL)
Number of 
Paired
CGM-YSI 
(n)
Percent of Matched Pairs in Each CGM System Glucose Range for Each YSI Glucose 
Range 
CGM (mg/dL)
40-60
61-80
81-120
121-160 161-200 201-250 251-300 301-350 351-400
351-400
>400
Table 7B. Concurrence of CGM System Readings and YSI Values within CGM System Ranges 
(Sample Table)
CGM
(mg/dL)
Number of 
Paired
CGM-YSI 
(n)
Percent of Matched Pairs in Each YSI Glucose Range for Each CGM Glucose Range YSI 
(mg/dL)
<40
40-60
61-80
81-120
121-
160
161-
200
201-
250
251-
300
301-
350
351-
400
>400
40-60
61-80
81-120
121-160
161-200
201-250
251-300
301-350
351-400
Table 8. CGM System Accuracy by Visit Number (Sample Table)
Day 
Number
Number of
Paired 
CGM-YSI
Mean
Absolute
Relative
Difference
(%)
Median
Absolute
Relative
Difference
(%)
Percent of CGM System Readings Within
Percent
15/15%
of
Reference
Percent
20/20%
of
Reference
Percent
30/30%
of
Reference
Percent
40/40%
of
Reference
Percent
Greater than
40/40% of
Reference
Day 1
Day 7
Day 14
Day 22
Day 30
Day 60
Day 90
Day 120
Day 150
Day 180
Table 10: CGM System between System Precision
Level of Mean 
Glucose 
Mean Difference 
(Sensor 1 - Sensor 
2) (mg/dL)
SD of Difference 
(mg/dL)
N Pairs
<= 70
71-180
> 180
All

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PARD
PCV