A Randomized Comparison of Transitioning From Insulin GLargine to Insulin Degludec usING a Bridging Dose of Glargine Versus Direct Conversion, in Patients With Type 1 Diabetes Mellitus - a Pilot Study
Phase: PHASE4
Conditions: Type 1 Diabetes
Sponsor: University of Washington

Brief Title: Comparison of Glargine to Degludec Insulin Transition With or Without a 
Bridging Glargine Dose ( GLIDING ) 
 
Official Title: A Randomized Comparison of Transitioning From Insulin GLargine to Insulin 
Degludec usING a Bridging Dose of Glargine Versus Direct Conversion, in 
Patients With Type 1 Diabetes Mellitus - a Pilot 
StudyNCT number: NCT04623086 
PI Name: Arthi Thirumalai MD 
Document name: Protocol 
IRB approval date: 08/13/2020

GLIDE Study 
V6.0_07.12.2019 
1 | P a g e  
 
 
1 
A randomized comparison of transitioning from insulin 
2 
GLargine to Insulin Degludec usING a bridging dose of 
3 
glargine versus direct conversion, in patients with type 1 
4 
diabetes mellitus – a pilot study 
5 
(GLIDING STUDY) 
6 
7 
8 
9 
INVESTIGATOR-SPONSORED STUDY PROPOSAL 
10 
11 
UNIVERSAL TRIAL NUMBER (UTN): U1111-1214-3257 
12 
13 
14 
Arthi Thirumalai, MBBS, Jing H. Chao, MD, Irl B. Hirsch, MD. 
15 
16 
Division of Metabolism, Endocrinology and Nutrition 
17 
Department of Medicine 
18 
University of Washington 
19 
1959 NE Pacific St, Box 356426, Seattle, WA 98195 
 
20 
 
21 
22 
Correspondence to: 
23 
24 
Arthi Thirumalai 
25 
Assistant Professor 
26 
1959 NE Pacific St, HSB C-209 
27 
UW Box # 357138, Seattle, WA 98196 
28 
Phone: 206-221-0521, Fax: 206-616-0499 
29 
Email: arthidoc@uw.edu 
30 
31 
32 
33 
34 
35 
36 
37 
38 
39 
 
 
40 

GLIDE Study 
V6.0_07.12.2019 
2 | P a g e  
 
 
 
41 
 
42 
Table of Contents 
43 
1. 
BACKGROUND AND SIGNIFICANCE ................. Error! Bookmark not defined. 
44 
2. 
SPECIFIC OBJECTIVES ........................................................................................... 4 
45 
3. 
RESEARCH DESIGN AND METHODS ................................................................... 5 
46 
3.1 
Study Hypothesis .................................................................................................. 5 
47 
3.2 
Endpoints ............................................................. Error! Bookmark not defined. 
48 
3.3 
Study type ............................................................................................................. 5 
49 
3.4 
Rationale for study Design ................................................................................... 6 
50 
3.5 
Study population: ................................................................................................. 7 
51 
3.6 
Inclusion Criteria .................................................................................................. 7 
52 
3.7 
Exclusion Criteria ................................................................................................. 7 
53 
3.8 
Withdrawal Criteria .............................................................................................. 8 
54 
3.9 
Patient Replacement ............................................................................................. 9 
55 
3.10 
Rationale for Study Population. ........................................................................ 9 
56 
3.11 
Visit Procedures ................................................................................................ 9 
57 
3.11.1 Screening Visit (Visit 1) ............................................................................. 10 
58 
3.11.2 CGM insertion visit (Visit 2) ...................................................................... 11 
59 
3.11.3 Telephone Encounters #1 ............................................................................ 13 
60 
3.11.4 Telephone Encounter #2: ............................................................................ 13 
61 
3.11.5 Telephone Encounter #3: ............................................................................ 13 
62 
3.11.6 CGM Removal and Download Visit (Visit 3) ............................................ 14 
63 
3.11.7 Exit Visit/Telephone encounter #4 (Visit 4) ............................................... 14 
64 
3.12 
Assessments for Efficacy ................................................................................ 14 
65 
3.13 
Assessments for Safety ................................................................................... 15 
66 
3.14 
Patient Compliance ......................................................................................... 15 
67 
4. 
STATISTICAL CONSIDERATIONS ...................................................................... 16 
68 
5. 
DATA HANDLING AND RECORD KEEPING: .................................................... 16 
69 
6. 
ETHICS..................................................................................................................... 17 
70 
7. 
STUDY SCHEDULE................................................................................................ 17 
71 
7.1 
Study Schedule ................................................................................................... 18 
72 
7.2 
Study Milestones ................................................................................................ 19 
73 
8. 
STUDY DRUGS AND MATERIALS ...................................................................... 19 

GLIDE Study 
V6.0_07.12.2019 
3 | P a g e  
 
 
74 
8.1 
Study medication(s) / devices(s) ........................................................................ 19 
75 
8.2 
Packaging and Labelling of Study Medication(s) .............................................. 19 
76 
8.3 
Storage and Drug Accountability of Study Medication(s) ................................. 20 
77 
8.4 
Auxiliary Supply ................................................................................................ 20 
78 
8.5 
Randomization and Blinding .............................................................................. 21 
79 
8.6 
Breaking of Blinded Codes ................................................................................ 21 
80 
9. 
CONCOMITANT ILLNESSES AND MEDICATIONS .......................................... 21 
81 
9.1 
Definitions .......................................................................................................... 21 
82 
10. 
ADVERSE EVENTS ............................................................................................. 22 
83 
10.1 
Definitions ...................................................................................................... 22 
84 
10.1.1 Adverse Event (AE) .................................................................................... 22 
85 
10.2 
Severity Assessment Definitions .................................................................... 23 
86 
10.3 
Relationship to study medication Assessment Definitions ............................. 23 
87 
10.4 
Outcome Categories and Definitions .............................................................. 23 
88 
10.5 
Collection, Recording and Reporting of Adverse Events ............................... 23 
89 
10.6 
Follow-up of Adverse Events ......................................................................... 24 
90 
10.7 
Pregnancy ....................................................................................................... 25 
91 
10.8 
Precautions/Over-dosage ................................................................................ 25 
92 
11. 
LIABILITY AND SUBJECT INSURANCE ......................................................... 25 
93 
12. 
EVALUABILITY OF SUBJECTS ........................................................................ 26 
94 
13. 
PREMATURE TERMINATION OF STUDY: ...................................................... 26 
95 
14. 
PUBLICATION PLAN .......................................................................................... 27 
96 
15. 
REFERENCES ...................................................................................................... 28 
97 
98 
99 
100 
101 

GLIDE Study 
V6.0_07.12.2019 
4 | P a g e  
 
 
102 
103 
1. BACKGROUND AND SIGNIFICANCE: 
104 
Insulin degludec (IDeg), an ultra-long-acting basal insulin, is increasingly used to 
105 
treat patients with type 1 diabetes (T1D). IDeg has a half-life of 25 hours and 
106 
duration of action exceeding 42 hours in patients with T1D (1,2) and as a result does 
107 
not require as stringent a dosing schedule as other basal insulins. It has been shown 
108 
to have a 4-fold lower within-patient variability in its pharmacodynamic response 
109 
compared   to  insulin   glargine  over  the  24  hour  dose  interval   (3).  The  rate  of 
110 
symptomatic and severe hypoglycemia in T1D patients has also been shown to be 
111 
lower with IDeg than insulin glargine (4). A recently published systematic review 
112 
and meta-analysis of 15 clinical trials comparing IDeg to insulin glargine showed 
113 
lower fasting plasma glucose and less nocturnal hypoglycemia with IDeg (5). The 
114 
total basal insulin dose invariably decreases with the transition to IDeg (6,7). The 
115 
lower  insulin  use  and  lower  rate  of  hypoglycemia  may  eventually  translate into 
116 
medical cost savings too (8). Moreover, patients have expressed more satisfaction 
117 
with their regimen and quality of life with IDeg compared to other agents in one 
118 
study that compared this objectively using questionnaires, before and after transition 
119 
(9). All of these factors give IDeg an advantage over other basal insulins currently in 
120 
the market. However, steady state concentration of IDeg is not reached until 2 to 3 
121 
doses are administered daily, and this may result in greater glycemic variability in 
122 
the  24  to  72  hours  following the  initiation  of  therapy with  IDeg (10).  There   is 
123 
currently no evidence-based guidance on how to minimize glucose excursions when 
124 
transitioning patients from their existing basal insulin to IDeg. The package insert for 
125 
IDeg suggests a 1:1 dose conversion from other basal insulin regimens to IDeg for 
126 
adult patients. However, this does not account for the time it takes IDeg to achieve 
127 
steady state and can result in worsening of glycemic control in the 48-72 hours after 
128 
the transition is made. Many practitioners at the University of Washington Diabetes 
129 
Clinic have seen better glycemic control within the first 12 to 24 hours in T1D 
130 
patients in whom we gave 50% of their usual dose of insulin glargine at bedtime 
131 
along with the first dose of IDeg. This leads to our hypothesis that a bridging therapy 
132 
involving the use of a reduced amount of patients’ prior basal insulin at the time of 
133 
initiating IDeg will lead to improved glycemic control in the first 24-72 hours on 
134 
IDeg, minimizing the morbidities associated with hyperglycemia and the need for 
135 
correctional insulin and also avoiding hypoglycemia resulting from over-correction 
136 
due to use of additional rapid-acting insulin. Additionally, we will follow what has 
137 
been done in prior clinical trials of conversion from other basal insulins to IDeg and 
138 
hence, convert them from their insulin glargine total daily dose to 80% of that dose 
139 
as IDeg (4). An improvement in the safety and ease of transitioning from the more 
140 
commonly used glargine to IDeg may greatly encourage more providers and patients 
141 
to adopt IDeg as the basal insulin of their choice. Another benefit would be knowing 
142 
how to transition patients back to their outpatient IDeg therapy when they are being 
143 
discharged home from an inpatient stay and were switched to insulin glargine during 
144 
their hospitalization, as IDeg is not formulary in many hospitals. The purpose of this 
145 
pilot study is to gain preliminary evidence of whether bridging with insulin glargine 
146 
while transitioning to IDeg provides better glycemic results in the transition period 
147 
compared to direct conversion. 

GLIDE Study 
V6.0_07.12.2019 
5 | P a g e  
 
 
148 148 
149 
2. ENDPOINTS AND OBJECTIVES: 
150 
Primary endpoint: 
151 
Change in percent time spent in target glycemic range (TIR, glucose 70-180 mg/dL, both 
152 
values included) in the 48 hours before and the 48 hours after the 1st dose of IDeg 
153 
Primary objective: 
154 
To  compare  the  mean  change  in  percent  time  in  range  (as  defined  by  the  primary 
155 
endpoint) between patients who transition directly to IDeg to the mean change in patients 
156 
who use a bridging dose of insulin glargine along with 1st dose of IDeg. 
157 
158 
Secondary end points: 
159 
These will include the following data obtained from their CGM download in the 48 hours 
160 
following the first dose of IDeg as measured as a difference compared to the 48 hours 
161 
preceding the dose: 
162 
1. Coefficient of variation of percent-time-in-range for each treatment within 
163 
each group 
164 
2. Nocturnal time in range of 70-180 mg/dL (between mid-night and 0600 hours, 
165 
both values included) 
166 
3. Percent time above 180 mg/dL (TAR-1), percent time above 250 mg/dL 
167 
(TAR-2) for each treatment within each group 
168 
4. Percent time below 70 mg/dL (TBR-1), percent time below 54 mg/dL (TBR- 
169 
2) for each treatment within each group 
170 
5. Number of correction boluses for each treatment within each group 
171 
172 
Secondary objectives: 
173 
To compare each of the secondary endpoints between patients who use a bridging dose to 
174 
patients who transition directly to IDeg. 
175 
176 
3. RESEARCH DESIGN AND METHODS 
 
177 
3.1 
Study Hypothesis: 
178 
Our hypothesis is that among patients who transition from insulin glargine to IDeg, those 
179 
who use a bridging dose of insulin glargine will not have a significant change, on average, 
180 
in  time  spent  in  target  glycemic  range  during  the  transition  period,  whereas,   those 
181 
transitioning directly to IDeg will have a significant change in this parameter. We further 
182 
hypothesize  that   those   using  the  bridging  dose  of  insulin   glargine   will   have less 
183 
hypoglycemia, less hyperglycemia and need fewer correction boluses than the direct- 
184 
conversion patients during the transition period. 
 
185 
3.2 
Study type: 
186 186 
187 
This   will   be   a   double-blind,   randomized,   single-center,   proof-of-concept   study. 
188 
Randomization will be stratified by use of insulin glargine once daily or twice daily at 
189 
baseline. Randomization will be conducted using permuted-block design with a block 
190 
size of 4, ensuring equal numbers of bridging and non-bridging patients in each of the 2 

GLIDE Study 
V6.0_07.12.2019 
6 | P a g e  
 
 
191 
resultant strata after every 4th patient is randomized within a stratum. The 2 strata with 
192 
blocked randomization within each stratum will result in 4 groups as follows: 
193 
1. Bridging Groups: 
194 
i. 
Patients transitioning from once daily insulin glargine to once daily IDeg with 
195 
a bridging dose of insulin glargine. 
196 
ii. 
Patients transitioning from twice daily insulin glargine to once daily IDeg 
197 
with a bridging dose of insulin glargine. 
198 
2. Direct-Conversion Groups: 
199 
i. 
Patients transitioning from once daily insulin glargine to once daily IDeg 
200 
without a bridging dose of insulin glargine (but with a bridging dose of 
201 
placebo solution to preserve blinding). 
202 
ii. 
Patients transitioning from twice daily insulin glargine to once daily IDeg 
203 
without a bridging dose of insulin glargine (but with a bridging dose of 
204 
placebo solution to preserve blinding). 
205 
206 
All patients will be instructed to use their own prescription insulin medications till before 
207 
the 1st  dose of IDeg. On the night they have to transition to IDeg, they will start using 
208 
study drugs for their basal insulin (see section 3.10.4). Starting with the 1st dose of IDeg, 
209 
their basal insulin will be from study drug only, till visit #3 (see section 3.10.6), at  which 
210 
time, they will resume their original insulin prescriptions. They will remain on their own 
211 
prescription short-acting insulin throughout the study. On the night of the transition, all 
212 
patients will be instructed to take their 1st  dose of IDeg and along with this, they will take 
213 
a second injection from a pre-filled syringe of a pre-specified dose of insulin glargine or 
214 
matched placebo (normal saline), that participants will collect from Investigational Drug 
215 
Services Pharmacy (IDS) on the same day. The dose will be calculated ahead of time by 
216 
study staff on  visit 2 (see under  section 3.10.2.1). Neither  the patients, nor the  research 
217 
staff will be aware of their randomization, which will be done by IDS. Patients will act as 
218 
their own controls, as we will collect glycemic data from 48 hours prior to the first dose 
219 
of IDeg, which will be compared to the data seen in the 48 hours after the first dose of 
220 
IDeg. During this observation period of the 48 hours before and after the first dose of 
221 
IDeg, no adjustments will be made to the calculated and recommended doses of insulin 
222 
glargine or IDeg. Patients will be followed for up to 1 week after the first dose of IDeg. 
223 
 
224 
3.3 
Rationale for study Design 
225 
Though IDeg is being increasingly used in clinical practice, there are no guidelines on 
226 
what  is  the  best  way  to  transition  patients  from  other  long-acting  insulins,  such  as 
227 
glargine, to IDeg. The package insert recommends 1:1 dose conversion from other basal 
228 
insulins to IDeg, but this does not account for the time taken by IDeg to achieve steady 
229 
state (typically 48-72 hours). There  is no  guidance on  what  to do in  those 48-72 hours. 
230 
Given the time taken for IDeg to achieve steady state, the period of transition from one 
231 
insulin to another, can result in significant glycemic variation in the 24-72 hours after the 
232 
first dose. We want to study how best to avoid or minimize this and the option of using a 
233 
small dose of their original long-acting insulin has anecdotal evidence of success in our 
234 
practice. 
235 235 

GLIDE Study 
V6.0_07.12.2019 
7 | P a g e  
 
 
236 
3.4 
Study population: 
237 
We aim to recruit patients with type 1 diabetes mellitus only. We will screen 50 patients 
238 
with  the  plan  to  randomize  approximately 40  patients  to  start  IDeg.  The  IDS  at the 
239 
University of Washington will randomize patients (1:1) to either receive or not receive a 
240 
bridging insulin glargine dose along with the 1st  dose of IDeg, within the stratified groups 
241 
of once- or twice-daily insulin-glargine regimens. 
242 
 
243 
3.5 
Inclusion Criteria 
244 
Patients must meet ALL inclusion criteria to be included in the study. 
245 
1. Patient age is 18-75 years. 
246 
2. Diagnosis of T1D of at least 1-year duration. 
247 
3. Has the ability to provide informed consent before any trial-related activities. 
248 
4. Treated with insulin glargine as their basal insulin in the 3 months preceding 
249 
screening visit. 
250 
5. Stable insulin regimen (defined as change of <20% in the total daily dose of 
251 
insulin and no change to the basal insulin agent) over the 3 months preceding the 
252 
screening visit. 
253 
6. Patient willing to dose their basal insulin at bedtime. 
254 
7. Hemoglobin A1c < 9% in the 3 months preceding screening visit. 
255 
8. Able to self-administer their insulin doses. 
256 
9. Able to do self-monitoring of blood glucose using a glucose meter and willing to 
257 
do this at least 2 times daily for patients using a CGM that requires calibration 
258 
prior to the study and 4 times daily for patients who were not using a CGM prior 
259 
to the study. 
260 
10. Agreeable to the use of a continuous glucose monitor (CGM) for the duration 
261 
required in the study. If already using a CGM prior to the study, then agreeable to 
262 
wearing the blinded study CGM concurrently during the study period. 
263 
11. Will be reachable by phone and/or email to comply with study procedures. 
264 
12. Will be able to comply with study procedures, per investigator’s opinion. 
265 
13. Patient agrees to not use correctional insulin unless BG ≥250 for the 48 hours 
266 
before and after 1st dose of IDeg. 
267 
268 
3.6 
Exclusion Criteria 
269 
Patient must not have ANY of the exclusion criteria to be included in the study. 
270 
1. Patients with eGFR <30 on at least 2 measurements within 1-year of the screening 
271 
visit. 
272 
2. History of myocardial infarction within 6 months preceding the screening visit. 
273 
3. Patients taking non-insulin medications for the glycemic management of T1D 
274 
(including metformin, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 
275 
inhibitors, thiazolidinediones, alpha-glucosidase inhibitors, pramlintide) 
276 
4. Known or suspected allergy to IDeg or one of its excipients. 
277 
5. Pregnant, planning to become pregnant in the next 3 months or breastfeeding. 
278 
6. Participation in a clinical trial with investigational drug within 1 month of the 
279 
screening visit or at present. 

GLIDE Study 
V6.0_07.12.2019 
8 | P a g e  
 
 
280 
7. Skin condition that prevents the insertion of the CGM. 
281 
8. Previously randomized and received drug in this study. 
282 
9. Presence of decompensated or poorly controlled psychiatric conditions. 
283 
10. Current known or suspected illicit substance use. 
284 
11. Any anticipated surgery or procedure in the next 14 days. 
285 
12. Patients using U-300 glargine as their basal insulin. 
286 
13. Patients using insulin afrezza as their short-acting insulin. 
287 
14. Use of glucocorticoid burst/pulse therapy within 14 days prior to screening visit 
288 
(chronic stable glucocorticoid doses are acceptable). 
289 
 
290 
3.7 
Withdrawal Criteria 
291 
Patients have the right to withdraw from the study at any stage and for any reason. 
292 
293 
Patients may be discontinued prematurely, by the investigator for any of the following 
294 
reasons: 
295 
• Emergence of a severe condition(s) such that, in the judgement of the investigator, 
296 
continuation in the trial would negatively impact the health of the patient. 
297 
• Lack of compliance with study medication or visits as judged by the Investigator. 
298 
• Patient lost to follow-up. 
299 
• Major protocol violation. 
300 
• Inter-current illness that, in the judgment of the investigator, should result in 
301 
premature discontinuation. 
302 
• Use of prohibited medications (see the Inclusion/Exclusion criteria) 
303 
• Onset of glucocorticoid burst/pulse therapy during the study period. 
304 
• Knowledge of new risks necessitating new benefit/risk evaluation. 
305 
• Patient voices intention to become pregnant in the immediate future. 
306 
307 
Patients must be discontinued for any of the following reasons: 
308 
• If Novo Nordisk determines that the study must be stopped, all patients will be 
309 
required to end participation at that time. 
310 
• Trial closed-out. 
311 
• Patient becomes pregnant. 
312 
313 
A patient will not be discontinued early from the study solely because of missing the 
314 
scheduled transition from insulin glargine to IDeg. The research staff will discuss the 
315 
matter with the patient and determine whether they feel he/she can continue moving 
316 
forward  in  the  study  following  all  study  procedures,  including  dosing.  If  after  this 
317 
discussion, the patient and the research team are in agreement about continuing in the 
318 
study, the investigator will decide if he/she may remain in the study. 
319 
320 
A subject cannot be considered lost to follow-up until the research center performs and 
321 
documents at least three (3) attempts to contact him by phone, email or letter. 
322 

GLIDE Study 
V6.0_07.12.2019 
9 | P a g e  
 
 
323 
3.8 
Patient Replacement 
324 
Patients  discontinuing from  the study will  not be replaced.  IDS  will  continue to assign 
325 
randomization   of  the  next   participant   to   a  specific   group,   based   on the original 
326 
randomization plan, when the next participant has completed screening procedures and is 
327 
ready for randomization. We will include data from all randomized participants in our 
328 
data analysis. 
329 
 
330 
3.9 
Rationale for Study Population 
331 
The main objective of our study is to determine if the use of a bridging dose of insulin 
332 
glargine is able to improve glucose control in first few days after the first dose of IDeg. 
333 
As  a  result,  we  will  recruit  participants  who  are  reasonably well  controlled  on their 
334 
baseline insulin regimens. We will exclude participants on non-insulin glucose-lowering 
335 
agents, as these can affect glycemic variability themselves and confound the results. We 
336 
are   not   excluding   patients   with   known   severe   hypoglycemia   or   hypoglycemia 
337 
unawareness in this study, as these are the patients who stand to benefit the most from the 
338 
transition from insulin glargine to IDeg. We are excluding patients with stage 4 or 5 CKD. 
339 
We will be excluding patients with a myocardial infarction in the last 6 months. These 
340 
patients will be excluded as they carry a higher risk that hypoglycemia or hyperglycemia 
341 
may result in mortality. 
342 
 
343 
3.10 Visit Procedures 
344 
Subjects will be screened for study eligibility and interest in participating in this study 
345 
(Screening Visit/Visit 1).  All subjects will have the study explained to them and sign the 
346 
informed  consent  prior  to  beginning  any  study  procedures.  Subjects  must  meet  the 
347 
inclusion criteria and have no exclusions. 
348 
349 
Randomization and treatment will be initiated only once eligibility is confirmed. 
350 
351 
There will be 4 phases to the study: 
352 
• A screening phase to establish eligibility that spans from screening visit till 
353 
insertion of study CGM (up to 2 weeks). 
354 
• A baseline observation phase to collect CGM data on their original insulin 
355 
glargine regimen, starting from insertion of study CGM to first dose of IDeg 
356 
administration (~3 days) 
357 
• A treatment phase starting from 1st to last dose of IDeg and consisting of at least 
358 
3 days of IDeg therapy (3-7 days). 
359 
• A follow-up phase from removal of study CGM to exiting from the study (till up 
360 
to 7 days after the last dose of IDeg) 

GLIDE Study 
V6.0_07.12.2019 
10 | P a g e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
361 3
6
1 
362 3
6
2 
363 3
6
3 
364 3
6
4 
365 3
6
5 
366 3
6
6 
 
367 3
6
7 
368 3
6
8 
369 3
6
9 
370 3
7
0 
371 3
7
1 
372 3
7
2 
373 373 
374 374 
375 375 
376 376 
377 377 
378 378 
379 379 
380 380 
381 381 
382 382 
383 383 
384 384 
385 385 
386 386 
387 387 
388 388 
389 389 
390 390 
391 391 
392 392 
393 393 
394 394 

GLIDE Study 
V6.0_07.12.2019 
11 | P a g e  
 
 
 
 
 
 
* 
C
o
u
l
d 
b
e 
e
x
t
e
n
d
e
d 
b
y 
2 
d
a
y
s 
i
f 
i
n
a
d
e
q
u
a
t
e 
C
G
M 
d
a
t
a 
n
o
t
ed on day 3 (see section 3.10.4) 
 
3.10.1 Screening Visit (Visit 1): 
Participants will be seen at the research wing of the Diabetes Care Center (DCC) at the 
University of Washington, Seattle, WA. Research staff will obtain informed consent after 
explaining study procedures. A detailed diabetes and medical history will be collected from 
the subjects. Their current medication regimen will be verified from them, particularly the 
actual number of units of the different insulins they are using. Subjects will undergo 
assessment of vital signs (pulse, blood pressure, weight, height, BMI) and a focused 
physical exam. If there is no available record of eGFR within the last year and/or 
hemoglobin A1c within the last 90 days, these will be obtained by phlebotomy at this visit. 
2 tubes of blood (1x 3cc lavender and 1x 4 cc lime green) will be drawn and sent off to 
measure hemoglobin A1c (by HPLC method) and basic metabolic panel to the UWMC 
clinical laboratory, if required. Subjects will be instructed to not alter their diet, alcohol 
consumption or exercise regimen from the time of study CGM insertion till 48 hours after 
the first dose of IDeg. 
 
If they are considered to be eligible for the study, then the research staff will contact IDS. 
IDS will then randomize the participant to one of the two arms within the two stratified 
groups. (Refer to sections 3.5 and 8.5 for details). Research staff will then contact the 
participant by phone or email to have them return for visit 2 for insertion of the study CGM. 
 
Important considerations for keeping things as uniform as possible in the study are as 
below: 
• We will ensure that all subjects on once daily insulin glargine are taking it at 
bedtime. Subjects who were taking it in the morning only at screening visit, will be 
switched to bedtime dosing at least 7 days prior to study CGM insertion. 
• We will ensure that subjects on twice daily insulin glargine at screening visit are 
taking their 2nd dose of the day at bedtime. 

GLIDE Study 
V6.0_07.12.2019 
12 | P a g e  
 
 
395 395 
 
396 
3.10.2 CGM insertion visit (Visit 2): 
397 
Participant will return to the DCC, within 2 weeks of visit 1, to meet with a research 
398 
coordinator who will assist with the insertion of the CGM (Dexcom G6). At this visit, 
399 
study staff  will  also  perform  any teaching  and  training  that  may be  required  for  the 
400 
participant to know how to use the CGM device. This visit needs to be conducted before 
401 
1200  hours.  They  will  be  given  CGM  supplies  to  last  up  to  1  week.  They  will be 
402 
instructed to keep the study CGM on at all times for this duration. If they have their own 
403 
CGM, then they will be allowed to keep that on in addition to the study CGM, should 
404 
they desire to do so. They will be instructed to replace the sensor, if needed. The study 
405 
CGM insertion day will be considered day 0. The next day will be day 1. Transition to 
406 
IDeg will be done on Day 3 as below. Subjects will be dispensed a log book in which 
407 
they will need to document carbohydrates consumed, exercise duration and time, timing 
408 
and doses of basal and bolus insulin (broken down as prandial and correction), self- 
409 
monitored blood glucose values, hypoglycemia symptoms and intervention for each day 
410 
they are in the study (from CGM insertion to removal) (See Appendix A and B). We  will 
411 
inquire about any change to concomitant medications and document insulin doses being 
412 
administered. 
413 
414 
415 
3.10.2.1 Insulin Dosing: 
416 
At visit 2, subjects will also be given written instructions on how to do the transition from 
417 
insulin glargine to IDeg. 
418 
419 
Calculation of IDeg dose 
420 
The dose of IDeg that subjects will be switched to will equal 80% of the total daily dose 
421 
of insulin glargine they reported using at visit 1. This reduction is what was done in the 
422 
clinical  trials  of  conversion  from  any  basal  insulin  to  IDeg  with  lower  risk  of 
423 
hypoglycemia (4). For example, if a subject was on 25 units of glargine at screening visit, 
424 
then they will need to switch to 20 units of IDeg (0.8 X 25 = 20). Number of units will be 
425 
rounded up to the next whole number if decimal points are ≥ 0.5 and rounded down if 
426 
<0.5. 
427 
428 
Timing of IDeg dose 
429 
To keep things consistent across participants, we will instruct all patients to start their 
430 
first dose of IDeg 3 days after the study CGM is inserted. The rationale for this is that the 
431 
first 24 hours of data on the CGM is not very accurate and after that we want 48 hours of 
432 
baseline glucose data on insulin glargine, prior to transitioning to IDeg. This will be used 
433 
later  as  their  baseline  to  compare  with  the  values  seen  on  IDeg.  Subjects  will  be 
434 
instructed  to  administer  their  first  dose  of  IDeg  at  2100  hours  on  the  3rd   day after 
435 
insertion of study CGM. They will then administer the same dose of IDeg every night for 
436 
5 ± 2 consecutive doses. 
437 
438 
Dosing of Insulin Glargine 
439 
Dosing of insulin glargine will depend on the group a subject is randomized to: 

GLIDE Study 
V6.0_07.12.2019 
13 | P a g e  
 
 
440 
441 
If randomized to bridging dose: 
442 
For  subjects  on  once-daily glargine,  up  to  day 2  after  study CGM  insertion they will 
443 
administer their usual insulin glargine dose at bedtime. On day 3, they will administer 
444 
50% of their usual glargine dose (using study drug) at 2100 hours along with only their 
445 
FIRST IDeg dose, as calculated. Thereafter, they will not administer insulin glargine till 
446 
after the 5 (± 2) days of IDeg are completed. 
447 
448 
For  subjects  on  twice-daily  glargine,  on  day  3  after  study  CGM  insertion  they will 
449 
administer their AM glargine dose as usual (i.e. 100%). On the same night, they will 
450 
administer 50%  of their bedtime glargine dose  (using study drug) at 2100 hours along 
451 
with  only  their  FIRST  IDeg  dose  as  calculated  above.  Thereafter,  they  will  not 
452 
administer insulin glargine till after the 5 (± 2) days of IDeg are completed. 
453 
454 
If randomized to direct conversion: 
455 
For  subjects  on  once-daily glargine,  up  to  day 2  after  study CGM  insertion they will 
456 
administer their usual insulin glargine dose at bedtime. On day 3, they will administer the 
457 
first dose of IDeg, as calculated above, at 2100 hours and a placebo solution in a dose 
458 
equivalent to 50% of their usual glargine dose. They will NOT  administer  any  insulin 
459 
glargine from that night till after 5 (± 2) days of IDeg are completed. 
460 
461 
For  subjects  on  twice-daily  glargine,  on  day  3  after  study  CGM  insertion  they will 
462 
administer their AM glargine dose as usual (i.e. 100%). On the same night, they will 
463 
administer the first dose of IDeg, as calculated above, at 2100 hours and a placebo 
464 
solution in a dose equivalent to 50% of their bedtime glargine dose. They will NOT 
465 
administer any insulin glargine from that night till after 5 (±  2) days of IDeg are 
466 
completed. 
467 
468 
Use of short-acting insulin 
469 
At the CGM insertion visit (visit 2), subjects will be instructed to use their prandial 
470 
insulin to carbohydrate ratios or pre-specified doses of prandial insulin the way they 
471 
would have otherwise, during the study. For the 48 hours before and after the first dose 
472 
of IDeg, however, all subjects will be instructed not to use any correctional insulin unless 
473 
their blood glucose is >250, both around meals and otherwise. While we understand that 
474 
subjects might be reluctant to allow their blood glucose to run in the 180-250 range 
475 
without correction, we feel this is a necessary part of our study protocol. The main reason 
476 
for this is that our primary study end point is time in range (TIR). If the change from 
477 
insulin  glargine  to  IDeg  results  in  more  time  in  the  180-250  range  in  patients  not 
478 
receiving the bridging dose of glargine, patients are likely to correct this aggressively 
479 
with the use of correctional insulin. This would dilute any measurable differences in our 
480 
primary end point (TIR). It would only potentially show differences in the  secondary end 
481 
points of dose and number of correctional insulin used. However, by telling them to avoid 
482 
bolusing till glucose rises above 250,  we  will be  able to discern  any differences in  TIR 
483 
that might arise from the change of basal insulin, while at the same time, not being unsafe 
484 
for the patients over a 96 hour period of time. 
485 

GLIDE Study 
V6.0_07.12.2019 
14 | P a g e  
 
 
486 
3.10.3 Telephone Encounters #1: 
487 
This will be on day 1 (i.e. the day after the study CGM is inserted). We will ensure that 
488 
the study CGM is working and the subject does not have any questions or concerns. 
489 
Study staff will also assist the subject with any troubleshooting, if necessary. Subjects 
490 
will be instructed to upload their CGM data on day 3, for research staff to review it. 
491 
Subjects  will  be instructed  not  to  alter their insulin  glargine dose for the  following 48 
492 
hours, till the night of day 3, when they transition to IDeg. We will inquire about any 
493 
adverse events and change to concomitant medications and document doses of insulin 
494 
being administered by patient. 
495 
 
496 
3.10.4 Telephone Encounter #2: 
497 
Research staff will review patient’s CGM data upload on day 3. We will inquire about 
498 
adverse  events,  any  change  to  concomitant  medications  and  also  document  doses of 
499 
insulin being administered. 
500 
If there is ≥ 38 hours of usable CGM data, then they will be instructed to proceed with 
501 
their first dose of  IDeg that night,  as scheduled.  In  order to obtain the bridging dose  of 
502 
insulin glargine or matched placebo, subjects will be instructed to proceed to IDS at the 
503 
University of Washington to collect their study drug the same day. 
504 
If there is < 38 hours of usable CGM data, then subjects will be instructed to wear their 
505 
CGM, per study protocol, while remaining on their original insulin regimen, and to again 
506 
upload CGM data on day 5. Research staff will review this data on day 5. 
507 
If there is ≥ 38 hours of usable CGM data from day 3-5, they will be instructed to proceed 
508 
with their first dose of IDeg that night, as scheduled. Subjects with < 38 hours of usable 
509 
CGM data will be discontinued from the study. 
510 
 
511 
3.10.5 Telephone Encounter #3: 
512 
This will be on day 4, i.e. the day after the first bedtime dose of IDeg (or on day 6 for 
513 
subjects  who  needed  to  repeat  baseline CGM  data collection).  We will  inquire about 
514 
adverse   events  and   any  change  to   concomitant  medications.  The   doses  of insulin 
515 
administered will be obtained and documented. The main purpose of this call is to ensure 
516 
that the subject implemented the transition from insulin glargine to IDeg, correctly. If it is 
517 
discovered that the subject forgot to transition, then they will be given repeat  instructions 
518 
to  dose on  night  of day 4.  If  it  is  discovered  that  the subject  executed  the transition 
519 
incorrectly, then they will need to undergo a 3-day “wash out period”, during which they 
520 
will resume their original insulin glargine regimen (with alterations as deemed necessary 
521 
by study physician on day 4), and then they will be instructed to execute the transition 
522 
again on night of day 7. If a subject performs the transition erroneously a second time, 
523 
he/she will be discontinued from the study and replaced by a new subject as the study 
524 
supplies allow. Subjects will be instructed not to alter their dose of IDeg for at least the 
525 
first 3 doses (i.e. 48 hours after 1st dose). 
526 

GLIDE Study 
V6.0_07.12.2019 
15 | P a g e  
 
 
527 
3.10.6 CGM Removal and Download Visit (Visit 3): 
528 
Subjects will come in approximately 8 ±  2 days after their CGM insertion. At this visit, 
529 
their study CGM will be removed and downloaded. We will inquire about adverse events 
530 
and  any  change  to  concomitant  medications.  We  will  collect  and  review  their study 
531 
logbook.  They  will  also  be  given  instructions  on  how  to  transition  back  to  insulin 
532 
glargine. 
533 
534 
Once-daily  glargine  users:  Approximately  24  hours  after  their  last  dose  of  IDeg, 
535 
subjects will be instructed to administer 50% of their original total daily dose of glargine 
536 
at bedtime. At 48 hours after their last dose of IDeg, they will return to their original 
537 
bedtime insulin glargine dose. 
538 
539 
Twice-daily  glargine  users: Approximately 24 hours after their last dose  of  IDeg, they 
540 
will administer 50% of their original bedtime insulin glargine dose. Approximately 36 
541 
hours  after  their  last  dose  of  IDeg  they  will  again  administer  50%  of  their original 
542 
morning insulin glargine dose. Approximately 48 hours after their last dose of IDeg, they 
543 
will resume their original insulin glargine dosing regimen (i.e. 50% of total dose twice 
544 
daily). 
545 
546 
Subjects will receive a gift card for $50 for participation in the study. 
547 
 
548 
3.10.7 Exit Visit/Telephone encounter #4 (Visit 4): 
549 
This  visit  will  be  approximately 7  days  after  the  study  CGM  removal  (+/-  2 days). 
550 
Subjects  will  be  called  to  see  if  they have  any  concerns  or  questions.  They  will be 
551 
instructed  to  follow  up  with  their  original  endocrinologist  for  any  further  insulin 
552 
adjustments. 
553 
 
554 
3.11 Assessments for Efficacy 
555 
On the screening visit (visit 1), if there is no available record of eGFR within the last year 
556 
and/or hemoglobin A1c within the last 3 months, these will be obtained by venipuncture 
557 
at this visit. The research team nurse or physician will perform this. 2 tubes of blood (1x 
558 
3cc lavender and 1x 4 cc lime green) will be drawn and sent off to measure hemoglobin 
559 
A1c (by HPLC method) and basic metabolic panel to the UWMC clinical laboratory. No 
560 
extra blood will be collected from the subjects. There will be no other instances of blood 
561 
collection during the study. These will help ensure that appropriate subjects are enrolled 
562 
in the study. 
563 
At the various telephone encounters, study staff will verify that the subjects are following 
564 
study instructions correctly. Specifically, on Telephone Encounter #2, only if adequate 
565 
usable CGM data is available on the data uploaded by the patient will they be allowed to 
566 
proceed with the transition (see section 3.11.4). 
567 
By measuring the time a patient spends in range (TIR = 70-180 mg/dL), we are assessing 
568 
the efficacy of the use of IDeg as a basal insulin. 
569 
570 

GLIDE Study 
V6.0_07.12.2019 
16 | P a g e  
 
 
571 
3.12 Assessments for Safety 
572 
The  primary safety concern  in  this  study is  the  risk  of  hypoglycemia. Hypoglycemia 
573 
management will be revised at screening visit to ensure appropriate education and all 
574 
medications and supplies needed to manage hypoglycemia will be prescribed at screening. 
575 
Subjects will be instructed that if they see BG <70 mg/dL on their personal CGM that 
576 
persists  longer  than  15  minutes  or  notice  symptoms  of  hypoglycemia  regardless  of 
577 
glucose reading, they need to perform a capillary blood glucose (CBG) measurement to 
578 
confirm if the meter shows a reading <70 mg/dL. If it does, they need to complete a 
579 
hypoglycemia  episode  form  (Appendix  B).  Upon  onset  of  a  hypoglycemic  episode, 
580 
subject is recommended to check CBG every 15 minutes until the value is ≥ 70 mg/dL 
581 
and/or  symptoms   have   resolved.   Repeated  CBG  measurements   and/or   symptoms, 
582 
occurring within a period of 60 minutes after onset on a hypoglycemic episode, will by 
583 
default be considered as one hypoglycemic episode until a succeeding CBG value is ≥ 70 
584 
mg/dL and/or symptoms have been resolved and should be reported as one hypoglycemic 
585 
episode.  CBG  measurements  <  70  mg/dL  or  hypoglycemic  symptoms  after  the  60 
586 
minutes period shall trigger the reporting of a new hypoglycemia episode and prompt  the 
587 
subject to fill out a new hypoglycemic episode form until a succeeding measurement is ≥ 
588 
70  mg/dL and/or  symptoms  have  been  resolved.  In  case  of  several  low  CBG values 
589 
within the 60 minutes interval, the lowest value is the one that will be reported as the 
590 
CBG value for the hypoglycemic episode but the start time of the episode will remain as 
591 
the  time  for  the  first  CBG  value  and/or  symptom.  Whenever  a  subject  completes a 
592 
hypoglycemia episode form, they should notify study staff within 24 hours. When they 
593 
notify study staff, details of the events around the low blood glucose (activity, food intake, 
594 
insulin administration) will be collected from them and then recommendations will be 
595 
made, as deemed necessary, by the study physician. 
596 
Hyperglycemia is the other risk of this study. Subjects will be instructed at screening to 
597 
notify  study  staff  within  24  hours  of  a  blood  glucose  >250.  Study  staff  will  try to 
598 
ascertain  from  the  subject  if  any  investigations  are  needed  and  make  management 
599 
recommendations, as deemed necessary, by the study physician. 
600 
By measuring the time a patient spends above or below range (>180  mg/dL or <70     601  
mg/dL) and assessing the frequency of use of correctional doses of short-acting insulin,   602 we 
are assessing how safe their glycemic management regimen is. 
603 
 
604 3.13 Patient Compliance 
605 Patient compliance to study procedures will be assessed during the telephone encounters. 606      
Compliance will be defined by the following (all 3 need to be met to be considered      607 
compliant), assessed during the 48 hours prior to and after the first dose of IDeg: 
 
608 
• 
No missed doses of basal insulin 
609 
• 
No missed doses of nutritional insulin with meals 
610 
• 
Wearing the study CGM for >19 hours a day 
611 
612 

GLIDE Study 
V6.0_07.12.2019 
17 | P a g e  
 
 
613 4. STATISTICAL CONSIDERATIONS: 
614   The primary objective of this pilot study is to calculate the change in percent time that    615    
BG is “in range” (TIR defined as 70-180 mg/dL) in the 48 hours before the first IDeg    616 dose 
vs. the 48 hours after the first dose, and to compare the mean of this change between 617 patients 
who are randomized to receive bridging glargine and those who are randomized  618 to not  receive 
bridging glargine.  Randomization will  be stratified by glargine use (once 619   vs. twice daily). 
For each patient, the TIR  in the 48 hours before first IDeg use will be   620   calculated,  as will 
the TIR in the 48 hours after first  IDeg use. The difference of these   621    values will then be 
calculated, and the mean of the differences compared between the    622 randomized arms.  Our  
primary  hypothesis  will  assume  that  the  “bridging  effect”  is 623 similar between patients who 
take glargine once daily and twice daily. However, we plan 624 an exploratory look at this 
assumption as a secondary objective. 
625 
626 If we assume the true change in TIR (before first  dose of  IDeg minus  after first dose of  627 
IDeg)  to be 0% for the  bridging group and  15%  for the  non-bridging group, and if  we 628 
assume a common standard deviation of 15% (meaning the distributions of change in TIR 629   are 
separated by 1 standard-deviation unit), then 20 patients in each group will provide   630 87% 
power to observe a statistically significant (at the two-sided level of .05) difference  631 in mean 
change of TIR. 
632 
633  As noted above, we’ll assess the magnitude of this difference as a function of once- vs.   634  
twice-daily glargine use.  With only 40 patients,  it’s highly unlikely that  a statistically   635    
significant interaction will be observed, but if the directions of the difference in mean    636     
changes  are the same in the once-daily vs. twice-daily groups we shall consider the      637 results 
to be consistent with each other. 
638 
639 
Secondary endpoints to be assessed in a descriptive manner include the following: 
640 
 
1. Coefficient of variation of TIR for each treatment within each group 
641 
2. Nocturnal time in range of 70-180 mg/dL (nTIR; both values included) (between 
642 
 
mid-night and 0600 hours) 
643 
3. Percent time above 180 mg/dL (TAR-1), percent time above 250 mg/dL (TAR-2) 
644 
 
for each treatment within each group 
645 
4. Percent time below 70 mg/dL (TBR-1), percent time below 54 mg/dL (TBR-2)  
646 
 
for each treatment within each group 
647 
5. Number of correction boluses for each treatment within each group 
648 
649     The overarching goal of  this pilot study is to collect data in a controlled setting on a     650  
variety of long-acting insulin regimens  and  gain  an idea if there is  a signal.  The data   651     
generated in this pilot study will be used to assist in the design of a future and larger     652 study 
where a more definitive comparison of efficacy will be conducted. 
653 
654 
655 
5.  DATA HANDLING AND RECORD KEEPING: 
656 
Study  information  will  be  collected  for  each  participant  by  research  staff  using  
657 
standardized Case xReport Forms (CRFs). CRFs will not report information about 

GLIDE Study 
V6.0_07.12.2019 
18 | P a g e  
 
 
658 treatment assignment in order to maintain blinding of treatment allocation. Forms will be 659 
stored at a secure location at the clinical site.  We expect that the majority of data will be  660 
collected via CRFs; however, other data sources, such as CGM download and laboratory  661  data,  
may be used.  All  study data will  be  entered  into  the Research  Electronic Data  662 Capture 
(REDCap),  a  web-based  data  entry  and  management  system  that  is  HIPPA 663   compliant 
and powered  by the  Institute of Translational Health Sciences, by research    664 staff.  The 
clinical data management procedures will be consistent with the International  665 Conference on 
Harmonisation (ICH E6) standards for Good Clinical Practice (GCPs)1. 
666 
667 
668 
6.  ETHICS: 
669 Ethical  considerations  related  to  the trial  include ensuring that  all  patients  receive an 670    
amount of insulin deemed appropriate by the clinicians for treatment of their diabetes    671 
mellitus both during the study period and following the conclusion of the study. Patients  672    
should have prompt treatment for both hypoglycaemia and hyperglycemia with blood    673 
glucose level of > 250mg/dl, as well as other possible complications related to treatment  674 with 
insulin, according to the standard of care following the guidance of their clinicians.  675  Potential 
participants will be sought from among the patients attending the study center,  676 University of 
Washington’s Diabetes Care Center in Seattle, WA.  An application will be 677 submitted for  
approval  by  University  of  Washington's  IRB  prior  to  conducting  the  678   research study.   
Potential candidates  will be identified and contacted according to the   679 procedures established 
by University of Washington’s IRB in compliance with local laws 680 protecting patient 
confidentiality and in accordance with the Declaration of Helsinki and  681  the  ICH GCP  
guidelines1.  Patients meeting the  inclusion and exclusion criteria of the   682   study will be 
identified by clinicians at the study center and offered the opportunity to    683  participate in the 
study.  An informed consent form will be given to all patients meeting  684   the inclusion and 
exclusion criteria.   This informed consent form will clearly offer the   685    possibility to opt out 
of any further contacts  with the study.  Written consent will be     686    obtained from all subjects 
invited to participate in the study after explaining again the    687  purpose  and  procedures  of  
the  study.  In  the  initial  contact  and  at  the  time  of  the 688 screening visit,  study subjects  
will  be encouraged  to  ask  questions  and  they will  be  689 reassured that they may withdraw 
from the study at any time.  Clinician investigators and 690  Novo Nordisk, will comply with all 
applicable  regulatory and legal requirements,  ICH  691 GCP guidelines  and  the  Declaration  of  
Helsinki  in  obtaining  and  documenting  the  692 informed consent1. 
693 
694 
695 
7.  STUDY SCHEDULE: 
696 The study  will  begin  recruitment  of  patients  immediately  following  the  approval  of 697  
University of Washington’s  IRB.  We plan to  recruit patients over  a 12-month period.  698  
Following the completion of patient recruitment and data collection, we plan to perform  699 data 
analysis and complete the integrated final study report over a 4-month period. 
700 

GLIDE Study 
V6.0_07.12.2019 
19 | P a g e  
 
 
701 
7.1 
Study Schedule 
 
Event 
Screening 
Visit 
Observation 
on Glargine 
Treatment 
with 
IDeg 
Follow- 
Up 
Up to 
2 weeks 
Day 0 
Day 1 
Day 3 
Day 4a 
Day  
7 ± 2a 
Day 
14 ± 2a 
Informed consent/ 
HIPPA 
x 
History/focused exam 
x 
Weight and vital signs 
x 
Documentation of insulin 
doses 
x 
x 
x 
x 
x 
x 
Documentation 
of 
concurrent medications 
x 
x 
x 
x 
x 
x 
Inquiry of adverse events 
x 
x 
x 
x 
x 
x 
Download of data from 
home glucose meter 
and/or CGMb 
x 
Labs 
x 
Eligibility 
x 
Randomization 
xc 
Study Drug Dispensation 
x 
Placement of study CGM 
x 
Daily Insulin logbook 
and hypoglycemia 
episode form 
dispensation 
x 
Telephone Encounter 
x 
x 
x 
x 
Collection of data from 
study CGM Upload 
x 
Study Drug 
Administration 
x 
x 
x 
Study 
Logbook/Hypoglycemia 
form Collection 
x 
Download 
data 
from 
study CGM 
xd 
702 
a.   Day 4, 7, and 14 may be extended by 2 days if patients do not have ≥ 38 hours of   
703 
 
usable study CGM data. See Section 3.11.4. 
704 
b. Download of data from patients’ CGM will be performed if patients wear their own 
705 
 
CGM prior to participating in the study. 

GLIDE Study 
V6.0_07.12.2019 
20 | P a g e  
 
 
706 
c. Randomization will be performed at  the  end  of  the  screening visit  after  patients 
707 
 
complete informed consent and have been deemed eligible to participate in the study. 
708 
d. Downloaded data include all endpoints listed under Section 3.2. 
709 
 
710 
 
 
 
 
711 
712 
713 
7.2 
Study Milestones 
Phase 1: 
IRB Approval 
Months 1-3 
 
 
Phase 2: 
Study 
Recruitment 
Months 4-15 
 
 
Phase 3: 
Data Analysis 
Months 16-19 
 
 
Phase 4: 
Publication 
Months 19+ 
714 
8.  STUDY DRUGS AND MATERIALS: 
715 
8.1 
Study medication(s) / devices(s) 
716 
• Insulin glargine, 100 units per mL injected subcutaneously daily, dosage as 
717 
determined by the clinician and study protocol. Manufacturer: Sanofi or Lilly 
718 
• IDeg, 100 units per mL injected subcutaneously daily, dosage as determined by 
719 
the clinician and study protocol. Manufacturer: Novo Nordisk. 
720 
• Placebo, 9g/L sodium chloride (normal saline) injected subcutaneously daily, 
721 
dosage as determined by the clinician and study protocol. 
722 
• Pen needles for injecting insulins. 
723 
• Dexcom G6 Mobile CGM System, inserted subcutaneously and worn for 3-10 
724 
days. Manufacturer: Dexcom, Inc. 
725 
• Glucose meter and 100 test strips, to perform self-monitoring of blood glucose, 
726 
one box dispensed per patient. Source: Diabetes Care Center. Manufacturer: 
727 
Accucheck Aviva Plus 
728 
 
729 8.2 Packaging and Labelling of Study Medication(s) 
730 
• IDS will package the  glargine  and  placebo  as  pre-filled  syringed  from  vials 731
 
 
identically. IDS will then label the syringes with dose, dosing instructions, and 2 
732 
 
patient identifiers based on study drug request order entered by research staff,  733
 
 
after being notified about treatment assignment by IDS. 
734 
• IDeg will be dispensed in the original manufacturer’s packaging,  and  IDS will  735
 
 
label IDeg with dose, dosing instructions, and 2 patient identifiers. 
736 
•   Dexcom G6 Mobile CGM System will be distributed to patients in its original   737
 
 
manufacturer packaging. 
738 
739 
Labelling of all medications and device will be in accordance with local law and study 
740 
requirements. 
741 

GLIDE Study 
V6.0_07.12.2019 
21 | P a g e  
 
 
742 8.3 Storage and Drug Accountability of Study Medication(s) 
743 All investigational  and/or  trial  products  received  will  be  accounted  for  by  the  IDS. 744     
Accountability logs are maintained for each product and dispensing is logged out as     745   
individual line items. Other than syringes and needles, subjects will return used, partly   746  used, 
and unused products, and these will be documented on the accountability logs and  747 may be 
retained for reconciliation. 
748 
749 All products will  be  stored  at  the  designated  temperature  (e.g.  refrigerated  or  room 750 
temperature) with temperature monitoring by the institutional system, TempTrak. This is 751 a 
continuous monitoring system  with  temperature time points  taken  every 15  minutes. 752 
Temperature  graphs  are  accessible  via  a  web-based  system.  TempTrak  sensors  are  753  
calibrated on a yearly basis. A second overlay is the use of Min/Max thermometers with  754  
manual recording of temperature daily on Mon - Fri. All Min/Max thermometers have a  755 
calibration certificate and are replaced prior to the expiration date. 
756 
757 Destruction of trial products are by incineration at an EPA approved site as contracted by 758 
the University of Washington Medical Center, currently by Clean Harbors Environmental 759   
Services.  If  preferred,  trial  products  can  be  shipped  back  to  the   Novo  Nordisk.   760 
Destruction of returns  can be performed  on an on-going basis. At study closure, all trial  761 
products  are  accounted  for and  any unused  remaining inventory can  be destroyed  or  762 
shipped back to Novo Nordisk. 
763 
764 At the time of study drug prescription and dispensing, research staff will provide patients 765  
with instructions to store the study drug at room temperature (below 86oF), keeping the   766  study 
drug away from direct heat and light.  Research staff will verify the conditions for  767  storage 
with patients on day 7±2 of study intervention period.   However, research staff   768  will not 
specifically require patients to measure or record the storage temperature of the  769 study drug 
because  of  the  short  duration  of  the  study intervention  period,  making  it 770 extremely 
unlikely for the  study drug to  be  compromised  as  long as  patients  properly 771    follow the 
storage instructions.   There will be no trial medication(s) dispensed to any    772 person not 
enrolled in the study.  IDS  will store unused study drug separately from used  773  study drugs in 
the refrigerator  at 36°F to 46°F (2°C  to 8°C) until the drug’s  expiration  774    date.   Patients 
will be instructed to return used/unused study drug, and  University of    775 Washington’s IDS 
will destroy the returned study drug per its standard protocol outlined  776 above. 
777 
 
778 8.4 Auxiliary Supply 
779  There is  no additional  item  or equipment  needed other than the ones  listed under the   780  
section of Study medication(s) / devices(s).  Patients may continue to use the following   781 
medications and devices during the study period: 
782 
•  A  rapid-acting  insulin  analogue  that  patients  normally  take  following  the   783
 
 
instructions of their clinicians, administered using either insulin pens or vials and 
784 
 
syringes 
785 
• Glucagon emergency kit, inject 1  mg/mL subcutaneously or  intramuscularly as 786
 
 
needed for treatment of severe hypoglycemia 

GLIDE Study 
V6.0_07.12.2019 
22 | P a g e  
 
 
787 
• Home glucose meters 
788 
• Home continuous glucose monitors 
789 
 
790 8.5 Randomization and Blinding 
791  We will perform a randomized, placebo-controlled intervention study to  minimise bias.  792 
Study participants will be randomized in a 1:1 ratio to one of two arms within 2 stratified 793  
groups groups (see Section 3.3).  After a participant has been randomized, a study drug   794   
request will be  sent to  IDS  to dispense the  study drug.   In  keeping with the blinded   795  
procedure, the patient and research staff will not be aware of treatment assignment. The  796  study 
drug request sent to  IDS will reflect only the dose of bridging insulin they should  797 receive. 
IDS  with then dispense a prefilled syringe of either insulin  glargine or matched 798  placebo to 
reflect this dose, directly to the research participant on  the day it needs to be  799   administered. 
Participants will then administer the study drug at home according to the   800  instructions  
provided  to  them  by  their  clinician  investigators  and/or  research  staff  801  according  to  
their  randomized  assignment  and  the  dosing  described  under  Section  802 3.11.2.1. 
803 
 
804 8.6 Breaking of Blinded Codes 
805    Breaking of the blinded code will not be applicable, as medical emergencies that may    806  
possibly associated with treatment with insulin will be no different between the control   807 and 
the study groups.  However, breaking the blinded code may be done if demanded by  808   the 
patient.   Whenever a code is broken, the person breaking the code must record the   809 time, date 
and reason, as well as his/her initials in the source documents.  All codes must  810   be kept 
throughout the study period.   Accountability of  all broken or unbroken codes    811 (hard copy 
or electronic) will be performed at or after trial closure. 
812 
813 
814 
9.  CONCOMITANT ILLNESSES AND MEDICATIONS: 
815 9.1 Definitions: 
816 Concomitant illness: any illness that is present at the start of the trial (i.e. at the first visit). 817 
Concomitant medication:  any medication  other  than  the  trial  product(s)  that  is  taken 818 
during the trial, including the screening and run-in periods. 
819 Details of all concomitant illnesses and medication must be recorded at trial entry (i.e. at  820 
the first visit). Any changes in concomitant medication must be recorded at each visit. If  821 the 
change influences the subject’s eligibility to continue in the trial, Novo Nordisk must 822 be 
informed. 
823 The information collected for each concomitant medication includes, at a minimum, start 824 
date, stop date or continuing, and indication. 
825 For  each  concomitant  illness,  date  of  onset,  date  of  resolution  or  continuing,  at  a  826 
minimum, should be recorded. 
827 
828 

GLIDE Study 
V6.0_07.12.2019 
23 | P a g e  
 
 
829 
 
830 
831 
832 
 
833 
834 
835 
836 
837 
838 
839 
840 
841 
842 
843 
844 
845 
846 
847 
848 
849 
850 
851 
852 
853 
854 
855 
856 
857 
858 
859 
860 
861 
862 
863 
864 
865 
866 
867 
868 
869 
870 
871 
872 
10.  ADVERSE EVENTS: 
10.1 Definitions 
The FDA approved version of the Prescribing Information or update thereof will be used 
for assessment of expectedness. 
 
10.1.1 Adverse Event (AE): 
An AE is any undesirable medical event occurring to a subject in a clinical trial, whether or 
not related to the trial product(s). This includes events reported from the first trial related 
activity after the subject has signed the informed consent and until post treatment follow-
up period as defined in the protocol. The following should not be recorded as AEs, if 
recorded as medical history/concomitant illness on the CRF at screening: 
• Pre-planned procedure, unless the condition for which the procedure was planned has 
worsened from the first trial related activity after the subject has signed the informed 
consent 
• Pre-existing conditions found as a result of screening procedures 
 
Clinical Laboratory Adverse Event: 
A clinical laboratory AE is any clinical laboratory abnormality regarded as clinically 
significant i.e. an abnormality that suggests a disease and/or organ toxicity and is of a 
severity, which requires active management, (i.e. change of dose, discontinuation of trial 
product, more frequent follow-up or diagnostic investigation). 
 
Serious Adverse Event (SAE): 
A serious AE is an experience that at any dose results in any of the following: 
• Death 
• A life-threatening* experience 
• In-patient hospitalisation or prolongation of existing hospitalization 
• A persistent or significant disability/incapacity 
• A congenital anomaly/birth defect 
• Important medical events that may not result in death, be life-threatening*, or require 
hospitalisation may be considered an SAE when, based upon appropriate medical 
judgement, they may jeopardise the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
• Suspicion of transmission of infectious agents 
*The term life-threatening in the definition of SAE refers to an event in which the subject was at risk of death 
at the time of the event. It does not refer to an event which hypothetically might have caused death if it was 
more severe. 
 
Serious Adverse Drug Reaction (SADR): 
An adverse drug reaction (ADR) is an adverse event (AE) for which a causal relationship 
to the trial product is at least possible i.e. causal relationship is conceivable and cannot be 
dismissed. Serious adverse reaction (SAR): Adverse event which fulfils both the criteria 
for a Serious Adverse Event and the criteria for an Adverse Reaction. 
 
Suspected Unexpected Serious Adverse Reaction (SUSAR): 

GLIDE Study 
V6.0_07.12.2019 
24 | P a g e  
 
 
873 
An SAE which is unexpected and  regarded  as  possibly  or  probably  related  to  the  
874 
trial/study product by the investigator. 
875 
876  Medical  Events  of  Special  Interest  (MESI): A MESI is (1) a medication error (e.g.  877  
wrong  drug  administration   or  wrong  route  of   administration)  or  (2)  a  suspected   878 
transmission of an infectious agent via the product 
879 
880 
Non-Serious Adverse Event: 
881 
A non-serious AE is any AE which does not fulfil the definition of an SAE. 
882 
 
883 
10.2 Severity Assessment Definitions: 
884 
• Mild: Transient symptoms, no interference with the subject’s daily activities 
885 
• Moderate: Marked symptoms, moderate interference with the subject’s daily activities 
886 
• Severe: Considerable interference with the subject’s daily activities, unacceptable 
887 
 
888 
10.3 Relationship to study medication Assessment Definitions: 
889 
• Probable: Good reasons and sufficient documentation to assume a causal relationship 
890 
• Possible: A causal relationship is conceivable and cannot be dismissed 
891 
• Unlikely: The event is most likely related to an etiology other than the trial product 
892 
 
893 10.4 Outcome Categories and Definitions: 
894 • Recovered:  Fully recovered  or  by  medical  or  surgical  treatment  the  condition  has 895   
returned to the level observed at the first trial related activity after the subject signed the 896 
informed consent 
897 • Recovering: The condition is improving and the subject is expected to recover from the 898 
event. This term should only be used when the subject has completed the trial 
899  • Recovered with sequelae:  As  a result  of the AE, the subject  suffered persistent  and   900   
significant disability/incapacity (e.g. became blind, deaf, paralysed). Any AE recovered 901 with 
sequelae should be rated as an SAE 
902 
• Not recovered 
903 
• Fatal 
904 
• Unknown 
905 
 
906 10.5 Collection, Recording and Reporting of Adverse Events 
907 All events meeting the definition of an adverse event will be collected and reported from  908 
the first study-related activity after the subject has signed the informed consent and until  909 the 
end of the posttreatment follow-up period as stated in the protocol. 
910 
911 
We intend to comply with all local legal, regulatory, and IRB requirements. 
912 
913 
All AEs will be reported on the Adverse Events form that will be completed by the study 
914 
staff, who are masked as to study treatment assignment, at each regular follow-up visits. 

GLIDE Study 
V6.0_07.12.2019 
25 | P a g e  
 
 
915  This  will  ensure  that  AEs  are  ascertained  in  an  unbiased  manner  using  the  same  916  
standardized  methodology  for  patients  in  both  treatment  arms.  Forms  will  include  917  
standardized questions relating to specific events of import in diabetic patients on either  918 of 
the  study treatment  arms,  as  well  as  any significantly abnormal  physical  findings  919  
identified on examination and any significantly abnormal laboratory results obtained on  920 the 
patient between visits or at the time of the visit.  AEs reported or ascertained between 921  clinic 
visits will be captured and  reported  at the  time of the  next scheduled visit.  Pre-  922 existing 
conditions (that  is,  any condition  that  was  known  to  be  present  prior to  the 923  signing of 
informed consent or was identified during the screening procedures) will not   924  be considered 
or recorded as AEs unless the condition worsens in intensity or frequency  925  after the initiation 
of study intervention.  Likewise, continuing AEs will not be reported   926 as AEs at subsequent 
visits unless they increase in severity or frequency between  visits,  927   they result in criteria for 
a SAE, and/or they resolve between visits.   The investigators   928  will report all adverse events 
including SAEs, SUSARs, serious adverse drug reactions   929  (SADRs) to the competent 
authority and independent ethics committee/IRB based upon  930  federal regulations and 
local/IRB policies.  The investigators will also  report all SAEs,   931     SUSARs, and SADRs to 
Novo Nordisk at the same time such events are reported to     932  regulatory authorities or within 
15 days from the investigators becoming aware of such   933 adverse events, whichever comes 
first. 
934 
935 
The investigators will collect the following information at minimum for each of these  
936 
events: 
 
937 
1. Study name 
938 
2. Patient identification (e.g. initials, sex, age) 
939 
3. Event (preferably a diagnosis) 
940 
4. Drug 
941 
5. Reporter identification (e.g. Name, or initials) 
942 
Also 6) Causality, and 7) Outcome 
943 
 
944 
10.6 Follow-up of Adverse Events 
945 
During and following a subject’s participation in a clinical trial, the investigators and  
946 
institution will provide adequate medical care to the study subject for any study-related 
947 
adverse events, including clinically significant laboratory values related to  the  study. 
948 
This medical care for study subjects will be provided regardless of their insurance status. 
949 
950 All adverse events classified as serious or severe or possibly/probably related to the trial  951     
product must be followed until the subject has recovered and  all queries have been      952  
resolved.  For  cases  of  chronic  conditions  follow-up  until  the  outcome  category  is  953 
“recovered” is not required, as these cases can be closed with an outcome of “recovering” 954 or 
“not recovered”. 
955 
956 
All other adverse events must be followed until the outcome of the event is “recovering” 
957 
(for chronic conditions), or “recovered” or until the end of the post-treatment follow-up 

GLIDE Study 
V6.0_07.12.2019 
26 | P a g e  
 
 
958 
959 
960 
 
961 
962 
963 
964 
965 
966 
967 
968 
969 
970 
971 
972 
 
973 
974 
975 
976 
977 
978 
979 
980 
981 
982 
983 
984 
985 
986 
987 
988 
989 
990 
991 
992 
993 
994 
995 
996 
997 
998 
999 
1000 
1001 
stated in the protocol, whichever comes first, and until all queries related to these AEs have 
been resolved. 
 
10.7 Pregnancy 
Study subjects will be instructed to notify the investigators immediately if they become 
pregnant. 
 
The investigators will report to Novo Nordisk any pregnancy occurring during the trial 
period. Reporting of pregnancy by investigators will occur within the same timelines 
described above for reporting of Adverse Events. 
 
Pregnancy complications should be recorded as adverse event(s). If the infant has a 
congenital anomaly/birth defect this must be reported and followed up as a serious adverse 
event. 
 
10.8 Precautions/Over-dosage 
All patients enrolled in the study will have access to and be instructed to wear a CGM from 
day 0 until the completion of study intervention. Patients may continue to wear the CGM 
as part of the standard of care for their diabetes beyond the study period. Use of a CGM 
has been shown to be effective in preventing hypoglycemia, which is a possible 
complication related to overdose of insulin, as well as morbidities and mortality related to 
hypoglycaemia (11). Clinician investigators and/or research staff will also provide patients 
with instructions on prompt recognition and proper treatment of hypoglycemia and 
prescribe patients with glucagon kit to be used for treatment of hypoglycemia as needed. 
Patients will have access to medical providers at the DCC by phone or e-care 
communication if additional guidance is needed in the event of overdose by the study drug 
during the study. 
 
 
11.  LIABILITY AND SUBJECT INSURANCE: 
During and following a subject’s participation in the clinical trial, the investigators and 
their institution will provide adequate medical care to the study subject for any study- 
related adverse events, including clinically significant laboratory values related to the 
study. This medical care for study subjects will be provided regardless of their insurance 
status. 
 
The investigators will be responsible for the conduct of the study and agree to defend, 
indemnify, and hold harmless Novo Nordisk, any of its parent companies, affiliates, or 
subsidiaries, and their respective officers, directors, employees, agents, representatives, 
distributors, salespersons, customers, licensees, and end-users from and against any claim, 
suit, demand, loss, damage, expense or liability imposed by any third party arising from or 
related to: (a) any breach of Novo Nordisk-investigators’ obligations or representations; or 
(b) Novo Nordisk-investigators’ negligent or grossly negligent use or willful misuse of the 
study drug, the results, or services derived therefrom. This 

GLIDE Study 
V6.0_07.12.2019 
27 | P a g e  
 
 
1002 
1003 
1004 
1005 
1006 
1007 
1008 
1009 
1010 
1011 
1012 
1013 
1014 
1015 
1016 
1017 
1018 
1019 
1020 
1021 
1022 
1023 
1024 
1025 
1026 
1027 
1028 
1029 
1030 
1031 
1032 
1033 
1034 
1035 
1036 
1037 
1038 
1039 
1040 
1041 
1042 
1043 
1044 
1045 
1046 
indemnification shall not apply in the event and to the extent that a court of competent 
jurisdiction or a duly appointed arbiter determines that such losses or liability arose as a 
result of Novo Nordisk’s gross negligence, intentional misconduct, or material breach of 
its responsibilities. 
 
 
12.  EVALUABILITY OF SUBJECTS: 
For all analyses, patients not meeting the compliance criteria of the study listed under 
Section 3.13 will not be included in the analyses. Clinician investigators will determine 
patients’ compliance with study drug based on patient’s recorded log and patients’ time 
spent wearing CGM after CGM data has been downloaded at the follow-up visit. We will 
include data from all randomized participants in our data analysis. The subjects or 
observations to be excluded, and the reasons for their exclusion will be documented and 
signed by the clinician investigators or staff prior to database release. The documentation 
will be stored together with the remaining trial documentation. 
 
PK and/or PD Modelling 
PK and PD modelling is not planned for this study. 
 
 
13. PREMATURE TERMINATION OF STUDY: 
All patients participating in the study will have already been taking insulin glargine prior 
to their enrolment in the study. Therefore, we do not anticipate patients developing any 
unforeseen adverse effect associated with the administration of insulin glargine. Similarly, 
we do not anticipate patients developing any unforeseen adverse effect associated with the 
administration of the placebo (normal saline). 
 
IDeg will be discontinued if a patient: 
• Experiences an SAE related to IDeg (with the exception of hypo- or 
hyperglycemia) or an intolerable AE, such as a persistent allergy or rash. 
• Becomes pregnant or breastfeeding 
• Withdraws consent for participation in the study 
 
Date and reason for drug discontinuation will be recorded on the relevant Case Report 
Form. Refer to Section 3.7 for Withdrawal Criteria.  All study discontinuations decided by 
the clinician investigators will be reviewed by University of Washington’s IRB. Patients 
discontinued from the study will be placed back on their original home insulin regimen and 
asked to follow up with their outpatient endocrinologists within 2-12 weeks, or at an 
interval deemed appropriate by their outpatient endocrinologists. Major attempts will be 
made to schedule an end-of-study follow-up phone call for all patients who are lost to 
follow-up during the course of the study. 
 
Patients who discontinue study drug or withdraw consent from the study prior to 
completion of data collection will not be replaced. 

GLIDE Study 
V6.0_07.12.2019 
28 | P a g e  
 
 
1047 
1048 
1049 
1050 
1051 
1052 
1053 
1054 
1055 
14.  PUBLICATION PLAN: 
Data and results generated from the study will be published or publicly presented at 
national and/or regional meetings in the form of abstracts, posters, and/or oral 
presentations. Clinician investigators will make good faith effort to publish data and results 
of this study in a peer reviewed scientific journal. The clinician investigators intend to 
register the study with clinicaltrials.gov. 

GLIDE Study 
V6.0_07.12.2019 
29 | P a g e  
 
 
1056 
1057 
1058 
1059 
1060 
1061 
1062 
1063 
1064 
1065 
1066 
1067 
1068 
1069 
1070 
1071 
1072 
1073 
1074 
1075 
1076 
1077 
1078 
1079 
1080 
1081 
1082 
1083 
1084 
1085 
1086 
1087 
1088 
1089 
1090 
1091 
1092 
1093 
1094 
1095 
1096 
1097 
1098 
1099 
1100 
1101 
1102 
1103 
1104 
 
15.  REFERENCES: 
1. Heise T, Nosek L, Bottcher SG, Hastrup H, Haahr H. Ultra-long-acting insulin degludec 
has a flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab 
2012; 14:944-950. 
2. Haahr H, Heise T. A review of the pharmacological properties of insulin degludec and 
their clinical relevance. Clin Pharmacokinet 2014; 53:787-800. 
3. Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin 
degludec: four times lower pharmacodynamic variability than insulin glargine 
under steady-state conditions in type 1 diabetes. Diabetes Obes Metab 2012; 
14:859-864. 
4. Lane W, Bailey TS, Gerety G, Gumprecht J, Philis-Tsimikas A, Hansen CT, Nielsen 
TSS, Warren M, Group I, Switch. Effect of Insulin Degludec vs Insulin Glargine U100 
on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized 
Clinical Trial. Jama 2017; 318:33-44. 
5. Liu W, Yang X, Huang J. Efficacy and Safety of Insulin Degludec versus Insulin 
Glargine: A Systematic Review and Meta-Analysis of Fifteen Clinical Trials. Int J 
Endocrinol 2018; 2018:8726046. 
6. Hamamoto Y, Honjo S, Fujimoto K, Tokumoto S, Ikeda H, Wada Y, Koshiyama H. 
Basal and Bolus Insulin Dose Changes after Switching Basal Insulin to Insulin Degludec 
in Patients with Type 1 Diabetes Mellitus: A Pilot Study. Clin Drug Investig 2017; 
37:845-852. 
7. Bohn B, Zimmermann A, Wagner C, Merger S, Dunstheimer D, Kopp F, Gollisch K, 
Zindel V, Holl RW, Initiative DPV. Real-life experience of patients starting insulin 
degludec. A multicenter analysis of 1064 subjects from the German/Austrian DPV 
registry. Diabetes Res Clin Pract 2017; 129:52-58. 
8. Lane WS, Weatherall J, Gundgaard J, Pollock RF. Insulin degludec versus insulin 
glargine U100 for patients with type 1 or type 2 diabetes in the US: a budget impact 
analysis with rebate tables. J Med Econ 2018; 21:144-151. 
9. Lecumberri E, Ortega M, Iturregui M, Quesada JA, Vazquez C, Orozco D. Quality-of-life 
and treatment satisfaction in actual clinical practice of patients with Type 1 diabetes 
mellitus (T1DM) and hypoglycemia treated with insulin degludec. Curr Med Res Opin 
2018; 34:1053-1059. 
10. Heise T, Korsatko S, Nosek L, Coester HV, Deller S, Roepstorff C, Segel S, Kapur R, 
Haahr H, Hompesch M. Steady state is reached within 2-3 days of once-daily 
administration of degludec, a basal insulin with an ultralong duration of action. J 
Diabetes 2016; 8:132-138. 
11. ICH. Guideline for Good Clinical Practice in International Conference on Harmonisation 
of Technical Requirements for Registration of Pharmaceutical for Human Use. 1996. 
12. Wolpert HA. Use of continuous glucose monitoring in the detection and prevention of 
hypoglycemia. J Diabetes Sci Technol 2007; 1:146-150 

GLIDE Study 
V6.0_07.12.2019 
30 | P a g e  
 
 
1105 
1106 
1107 
1108 
1109 
1110 
1111 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1112 
1113 
1114 
1115 
1116 
1117 
1118 
1119 
1120 
1121 
1122 
1123 
1124 
1125 
1126 
1127 
1128 
1129 
APPENDIX A: Sample Subject Daily Insulin Logbook, version-1.0 
Trial ID: U1111-1214-3257 
Subject No. XX Subject Initials: ABC Subject DOB: MMDDYY 
Date: MMDDYY  Study Day: # 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* To be used only if needed. NOTE: please use these fields to enter any snacks consumed 
as well. 
 
Did you exercise today? [ ] yes or [ ] no 
If yes, then please specify when and how long: from  
to  
(hh:mm) 
Time 
point 
Time 
(hh:mm) 
BG 
value 
(mg/dL) 
Carbohydrates 
consumed 
(grams) 
Bolus insulin 
dose    
NUTRITIONAL 
(units) 
Bolus insulin 
dose   
CORRECTION 
(units) 
Basal 
insulin 
dose 
(units) 
Before 
breakfast 
Before 
lunch 
Before 
dinner 
At 
bedtime 
*Extra 
time 
point #1 
*Extra 
time 
point #2 
*Extra 
time 
point #3 

GLIDE Study 
V6.0_07.12.2019 
31 | P a g e  
 
 
1130 
1131 
1132 
1133 
1134 
1135 
1136 
1137 
1138 
1139 
1140 
1141 
1142 
1143 
1144 
1145 
1146 
1147 
1148 
1149 
1150 
1151 
1152 
1153 
1154 
1155 
1156 
1157 
1158 
1159 
1160 
1161 
1162 
1163 
1164 
1165 
1166 
1167 
1168 
1169 
1170 
1171 
1172 
1173 
1174 
1175 
1176 
 
APPENDIX B: Sample Subject Hypoglycemia Episode Form, version 1.0 
(see Section 3.12 for details on directions to fill out this form) 
 
Trial ID: U1111-1214-3257 
Subject No. XX Subject Initials: ABC Subject DOB: MMDDYY 
Date: MMDDYY  Study Day: # 
1. When did the low BG start?  
(hh:mm) 
2. What was the lowest BG value during the episode?  
(mg/dL) 
3. Did you experience any of the following symptoms with this low BG? 
[ ] No or [ ] Yes (check all that apply) 
[ ] Sweating 
[ ]Trembling 
[ ] Feeling hungry 
[ ] Rapid or irregular heartbeat 
[ ]Feeling confused 
[ ]Feeling drowsy 
[ ]Speech difficulty 
[ ]Visual disturbances 
[ ]Odd behavior 
[ ]Impaired balance 
[ ]Reduced coordination of movements 
[ ]Headache 
[ ]Feeling discomfort or unease 
[ ]Seizure 
[ ]Loss of consciousness 
[ ]Other 
4. Were you able to manage it by yourself? [ ] yes or [ ] no. If no, please fill out Q9- 
12 as well. If yes, please skip Q9-12. 
5. How did you treat the low BG?   
 
6. When did the low BG resolve?  
(hh:mm) 
7. Did this episode happen in relation to physical activity? [ ]Yes or [ ]No 
If yes, then what were you doing?   
 
8. Were you asleep when the low blood glucose happened? [ ]Yes or [ ]No 
9. Who assisted in treatment of the episode?   
 
10. Where was the treatment administered?   
 
11. What treatment was provided to treat the episode?   
 
12. Were your symptoms alleviated by this treatment? [ ]Yes or [ ] No