Clinical Characteristics, Anti-hyperglycaemic Treatment Pattern and Target Attainment of Type 2 Diabetes Mellitus Patients in Older Population With or Without Albuminuria in China: A Nationwide Cross-sectional Study
Conditions: Type 2 Diabetes Mellitus
Sponsor: Boehringer Ingelheim

ABCD
001-MCS-90-118_RD-01 (7.0) / Saved on: 09 Nov 2015
TITLE PAGE
Non-intervention study Protocol
Document Number:
c14196017-01
BI Study Number:
1218.174
BI Investigational
Product(s):
Not applicable
Title:
Clinical characteristics, anti-hyperglycaemic treatment pattern 
and target attainment of type 2 diabetes mellitus patients in older 
population with or without albuminuria in China: A nationwide 
cross-sectional study
Brief lay title
None
Protocol version 
identifier:
2.0
Date of last version of 
protocol:
29 Sep 2016
PASS:
No
EU PAS register 
number:
Not applicable
Active substance:
Not applicable
Medicinal product:
Not applicable
Product reference:
Not applicable
Procedure number:
Not applicable
Marketing authorisation 
holder(s):
Not applicable
Joint PASS:
No
Research question and 
objectives:
To investigate the level of glucose control, current anti-
hyperglycaemic and the anti-hypertension/Lipid Lowering/anti-
platelet treatment patterns, occurrence of the hypoglycaemia, 
and other potential factors associated with the level of glucose 
control in older population of T2DM in China
Country(-ies) of study:
China
Author:

Boehringer Ingelheim
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Marketing authorisation 
holder(s):
Not applicable
In case of PASS, add:
MAH contact person:
Not applicable
In case of PASS, add:
<EU-QPPV:>
Not applicable
In case of PASS, add:
<Signature of EU-
QPPV:>
Not applicable
Date:
20 Dec 2016
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Proprietary confidential information
© 2016 Boehringer Ingelheim International GmbH or one or more of its affiliated companies. All rights reserved.
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission

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1.
TABLE OF CONTENTS
1.
TABLE OF CONTENTS....................................................................................... 3
2.
LIST OF ABBREVIATIONS................................................................................ 5
3.
RESPONSIBLE PARTIES.................................................................................... 6
4.
ABSTRACT........................................................................................................... 7
5.
AMENDMENTS AND UPDATES....................................................................... 9
6.
MILESTONES..................................................................................................... 13
7.
RATIONALE AND BACKGROUND................................................................ 14
8.
RESEARCH QUESTION AND OBJECTIVES ................................................. 15
9.
RESEARCH METHODS .................................................................................... 16
9.1
STUDY DESIGN............................................................................................ 16
9.2
SETTING........................................................................................................ 16
9.2.1
Study population ..................................................................................... 16
9.2.2
Visit schedule.......................................................................................... 17
9.3
VARIABLES .................................................................................................. 18
9.3.1
Primary outcome ..................................................................................... 18
9.3.2
Secondary outcomes................................................................................ 18
20
9.3.4
Safety events ........................................................................................... 20
9.4
DATA SOURCES........................................................................................... 20
9.5
STUDY SIZE.................................................................................................. 20
9.6
DATA MANAGEMENT................................................................................ 21
9.7
DATA ANALYSIS......................................................................................... 21
9.7.1
Analysis population................................................................................. 21
9.7.2
Primary analyses ..................................................................................... 21
9.7.3
Secondary analyses ................................................................................. 22
22
9.8
QUALITY CONTROL................................................................................... 22
9.9
LIMITATIONS OF THE RESEARCH METHODS...................................... 23
9.10
OTHER ASPECTS ......................................................................................... 23
9.10.1
Study compliance, data protection and study result................................ 23
9.10.2
Study approval, patient information and informed consent .................... 23
9.10.3
Data quality assurance............................................................................. 24
9.10.4
Study records........................................................................................... 24

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9.10.4.1
Source documents............................................................................24
9.10.4.2
Direct access to source data and documents....................................24
9.10.4.3
Statement of confidentiality.............................................................25
10.
PROTECTION OF HUMAN SUBJECTS .......................................................... 26
11.
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS....................................................................................................... 27
11.1
Definitions of adverse events.......................................................................... 27
11.2
Adverse Reaction and Fatal adverse event reporting...................................... 28
11.3
Reporting to health Authorities....................................................................... 30
12.
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
............................................................................................................................. 31
13.
REFERENCES .................................................................................................... 32
13.1
PUBLISHED REFERENCES......................................................................... 32
13.2
UNPUBLISHED REFERENCES................................................................... 32
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS.............................................. 33
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS .............................. 34
ANNEX 3. ADDITIONAL INFORMATION.............................................................. 41

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2.
LIST OF ABBREVIATIONS
ACR
Albumin-to-Creatinine Ratio
ADA
American Diabetes Association
AE
Adverse Event
ADR
Adverse Drug Reaction
ANOVA
Analysis of Variance
BMI
Body Mass Index
CA
Competent Authority 
CDS
Chinese Diabetes Society
CKD
Chronic Kidney Disease
CKD-EPI
CKD Epidemiology Collaboration 
CI
Confidence Interval
CRA
Clinical Research Associate
CRF
Case Report Form
DPP-4
Dipeptidyl Peptidase-4
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
eGFR
Estimated Glomerular Filtration Rate
FAS
Full Analysis Set
FDA
Food and Drug Administration
FPG
Fasting Plasma Glucose
GCP
Good Clinical Practice
GLP-1
Glucagon Like Peptide-1
GPP
Good Pharmacoepidemiology Practices
HbA1c
Glycated Haemoglobin A1c
HDL-C
High Density Lipoprotein Cholesterol
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ISF
Investigator Site File
MAH
Marketing Authorisation Holder 
OAD
Oral Antidiabetic Drug
PPG
Postprandial Plasma Glucose
LDL-C
Low Density Lipoprotein Cholesterol
SADR
Serious Adverse Drug Reaction
SAE
Serious Adverse Event
SEAP
Statistical and Epidemiological Analysis Plan 
SCr
Serum Creatinine
SOP
Standard Operating Procedures 
SUSAR
Suspected Unexpected Serious Adverse Reaction 
T2DM
Type 2 Diabetes Mellitus
TC
Total Cholesterol
TCM
Trial Clinical Monitor
TG
Triglyceride
UA
Uric Acid
UAE
Urinary Albumin Excretion

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3.
RESPONSIBLE PARTIES
BI Contact Person:
 
Trial Clinical Monitor
Address:
Contact details:
Principal Investigator:
Address: 

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4.
ABSTRACT
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
Not applicable
Name of active ingredient:
Not applicable
Protocol date:
Study
number:
Version/Revision:
Version/Revision 
date:
29 Sep 2016
1218.174
2.0
20 Dec 2016
Title of study:
Clinical characteristics, anti-hyperglycaemic treatment pattern and 
target attainment of type 2 diabetes mellitus patients in older 
population with or without albuminuria in China: A nationwide cross-
sectional study
Rationale 
and 
background:
China has the largest number of people with diabetes in the world, with 
the majority of the patient population over 60 years old and living in 
urban areas. However no data are available specifically on the clinical 
characteristics of the older population with type 2 diabetes mellitus 
(T2DM) in China
Research question 
and objectives:
To investigate the level of glucose control, current anti-
hyperglycaemic and the anti-hypertension/Lipid Lowering/anti-platelet 
treatment patterns, occurrence of the hypoglycaemia, 
and other 
potential factors associated with the level of glucose control in older 
population of T2DM in China
Study design:
This is a multi-centre, cross-sectional, non-interventional study
Population:
Outpatients with T2DM aged 60 years or older in China
Variables:
Primary outcome

Proportion of patients attaining blood glucose control target defined 
as HbA1c<7% 
Secondary outcomes

Renal function level of patients

Treatment regimens for T2DM that patient are currently taking

Proportion 
of 
macro-vascular 
and 
micro-vascular 
diabetic 
complications

Proportion of Hypoglycaemic occurrence

Proportion of Hypoglycaemia leading to therapy change

Proportion of Anti-hypertension therapy usage

Proportion of Lipid Lowering therapy usage

Proportion of Anti-Platelet therapy usage

Treatment adherence to Chinese T2DM guideline 2013
Data sources:
Examination report, outpatient medical Chart or other original medical 
record
Study size:
1500 patients

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Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
Not applicable
Name of active ingredient:
Not applicable
Protocol date:
Study 
number:
Version/Revision:
Version/Revision 
date:
29 Sep 2016
1218.174
2.0
20 Dec 2016
Data analysis:
Descriptive statistics will be used to summarize the data in the study. 
The proportion of patients attaining HbA1c <7% will further be 
tabulated by subgroups of demographic and clinical characteristics. A 
logistic regression model will be conducted to identify associations 
between overall blood glucose control and demographic and clinical 
characteristics.
Milestones:
Start of data collection: 28 Feb 2017
End of data collection: 04 Sep 2017
Final report of study results: 31 Dec 2017

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5.
AMENDMENTS AND UPDATES
Number
Date
Section of 
study
protocol
Amendment or update
Reason
<1>
29 Nov2016
Front 
Page
Research question and objectives: 
To investigate the level of glucose 
control, 
current 
anti-
hyperglycaemic 
and 
the
anti-
hypertension/Lipid Lowering/anti-
platelet 
treatment 
patterns, 
occurrence of the hypoglycaemia, 
and
other 
potential 
factors 
associated with the level of glucose 
control
in older population of 
T2DM in China.
According to the 
conclusion of the 
investigator 
meeting.
The 
Secondary 
Objectives have 
been amended.
<2>
29 Nov2016
4
Research question and objectives: 
To investigate the level of glucose 
control, 
current 
anti-
hyperglycaemic and the
anti-
hypertension/Lipid 
Lowering/anti-platelet 
treatment 
patterns, 
occurrence 
of 
the 
hypoglycaemia, 
 
and 
other 
potential factors associated with 
the level of glucose control in 
older population of T2DM in 
China.
According to the 
conclusion of the 
investigator 
meeting.
The 
Secondary 
Objectives have 
been amended.
<3>
29Nov2016
4
add 6 secondary outcomes

Proportion of Hypoglycaemic 
occurrence

Proportion of Hypoglycaemia 
leading to therapy change.

Proportion
of 
Anti-
hypertension therapy.

Proportion of Lipid Lowering 
therapy.

Proportion
of 
Anti-Platelet 
therapy.

Treatment 
adherence 
to 
Chinese 
T2DM 
guideline 
2013.
The 
Secondary 
Objectives have 
been 
amended. 
Variable 
has 
been 
changed 
accordingly.

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<4>
29Nov2016
4
Milestones:   
Start of data collection: 28 Feb
2017
End of data collection: 04 Sep
2017
Final report of study results: 31 
Dec 2017
According 
the 
protocol 
amendment, the 
milestone 
has 
been changed.
<5>
29Nov2016
6
Milestones:   
Start of data collection: 28 Feb
2017
End of data collection: 04 Sep
2017
Final report of study results: 31 
Dec 2017
According 
the 
protocol 
amendment, the 
milestone 
has 
been changed.
<6>
29Nov2016
8
The secondary objectives are:

to 
investigate 
the 
anti-
hyperglycaemic 
treatment 
patterns of the study population.

to investigate occurrence of the 
hypoglycaemia 
and 
hypoglycaemia 
leading 
to 
therapy change.

to 
investigate 
the 
anti-
hypertension/Lipid 
Lowering/anti-platelet 
treatment patterns of the study 
population.

to 
investigate 
the
clinical 
characteristics
of the study 
population.

to 
investigate 
clinical 
characteristics, 
anti-hyperglycaemic treatment 
pattern 
and 
blood 
glucose 
control in older T2DM patients 
with albuminuria.

to 
investigate 
treatment 
adherence to Chinese T2DM 
guideline 2013
According to the 
conclusion of the 
investigator 
meeting.
The 
Secondary 
Objectives have 
been amended.
<7>
29Nov2016
9.2.1
Figure 1 – Study Flow of the 
cross-sectional study:
Blood test:HbA1c, FPG, LDL-C, 
HDL-C, TC, TG, Scr, UA; Urine 
test: Albuminuria, Urine WBC
As the Second 
Objectives have 
been 
changed, 
the 
visit 
schedules 
have 
been 
changed 
accordingly.

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<8>
29Nov2016
9.2.1
Inclusion Criteria #2:
Outpatient with confirmed T2DM 
(According 
to 
Definition 
and 
Diagnosis Diabetes Mellitus :World 
Health Organization 1999 [R04-
1142] )
The 
diagnosis 
criteria changed
according to the 
decision 
of 
investigator 
meeting.
<9>
29Nov2016
9.2.2
Amend following
information
under 
Collect 
the 
following 
information
o
Personal health history 

Diabetes Mellitus history

Chronic 
Kidney 
Disease 
history

Anti-Hypertension 
therapy 
history

Lipid 
Lowering 
therapy 
history

Anti-Platelet therapy history

hypoglycaemic history
o
Family health history (e.g., 
diabetes, hypertension, and 
Chronic kidney diseases)
o
Laboratory tests

HbA1c

Albuminuria

Urine WBC

Fasting plasma glucose (FPG), 
(examined within one month 
prior to the visit)

Serum creatinine (SCr), uric 
acid 
(UA), 
high 
density 
lipoprotein cholesterol (HDL-
C), low density lipoprotein 
cholesterol 
(LDL-C), 
triglyceride 
(TG), 
total 
cholesterol (TC) (If examined 
within three months prior to 
the visit，record the result; if 
examined 
without 
 
three 
months prior to visit, record 
the date of last examination 
and 
re-examine 
by 
investigator’s judgment.)
As the Second 
Objectives have 
been 
changed, 
the 
visit 
schedules 
have 
been 
changed 
accordingly

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<10>
29Nov2016
9.3.2
Add following secondary 
outcomes

Proportion of Hypoglycaemic 
occurrence

Proportion of Hypoglycaemia 
leading to therapy change.

Proportion of Anti-
hypertension therapy.

Proportion of Lipid Lowering 
therapy.

Proportion of Anti-Platelet 
therapy.

Treatment adherence to 
Chinese T2DM guideline 2013
As the Second 
Objectives have 
been 
changed, 
some
secondary 
outcomes 
have 
been 
added
accordingly.
<11>
29Nov2016
9.3.3
PPG has been deleted.
As the Second 
Objectives 
have 
been changed, the 
visit 
schedules 
have 
been 
changed 
accordingly.
<12>
29Nov2016
9.7.1
The 
definition 
of 
FAS-
Albuminuria has been updated, 
which takes urinary tract infection 
into account.
Based 
on 
investigators’
consideration for 
determining 
micro-
albuminuria 
diagnosis.
<13>
29Nov2016
9.7.3
The 
analyses 
for 
additional 
secondary endpoints have been 
added.
As the secondary 
endpoints 
have 
been updated, the 
corresponding 
analyses 
have 
been added.
<14>
29Nov2016
13
R04-1142
Definition, diagnosis 
and 
classification 
of 
diabetes 
mellitus and its complications: 
report of a WHO consultation. Part 
1: diagnosis and classification of 
diabetes 
mellitus. 
WHO/NCD/NCS/99.2. 
Geneva: 
World 
Health
Organization, 
Department of Noncommunicable 
Disease Surveillance, , 1 - 59 
(1999)
Diabetes 
diagnosis criteria 
Changed as the 
investigator 
meeting decision. 
So the reference 
document 
changed.

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6.
MILESTONES
Milestone
Planned Date
Start of data collection
28 Feb 2017
End of data collection
04 Sep 2017
Final report of study results:
31 Dec 2017

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7.
RATIONALE AND BACKGROUND
Type 2 diabetes mellitus (T2DM) is a progressive disease caused by insulin resistance and 
decreased pancreatic β-cell function. The management of diabetes is very important in
preventing diabetes complications, as well as long-term health problems. Despite a wide 
range of available therapies, the epidemic continues. Worldwide, the International Diabetes 
Federation estimates the global prevalence of diabetes in the older population (60–79 years) 
to be 18.6%—more than 134.6 million people—accounting for over 35% of all cases of 
diabetes in adults [R14-1806]. In 2013, China reported the highest number of people with 
diabetes in the world at 113.9 million and a prevalence of 11.6%, with a majority of the 
diabetes population over the age of 60 years and living in urban areas [R13-5351]. The high 
prevalence of diabetes is a public health issue as it increases the risk of other age-related 
diseases [R16-4557].
Diabetes in older adults is multifaceted in aetiology, caused by a combination of genetic and 
environmental factors. The risk factors include family history, age, lifestyle, illnesses and 
medications, as well as age-related decline in body functions [P16-10791]. The clinical 
profile of older patients with T2DM and their response to glycaemic control regimens are 
often different from that in younger patients [P13-17218]. Older patients with T2DM are at 
greater risk of hypoglycaemia [R16-4558]and other complications such as stroke and diabetic 
nephropathy [R16-4559]. Albumin is an abundant serum protein, which is undetectable in 
urine under normal health conditions. Therefore, increased urinary albumin excretion is an 
early clinical manifestation of diabetic nephropathy. Albuminuria is also associated with 
cardiovascular disease in patients with or without diabetes. Moreover, (micro-) albuminuria is 
often present at diagnosis in patients with T2DM and may reflect both underlying 
cardiovascular disease and diabetic nephropathy. Albuminuria is hence an established 
biomarker that identifies patients with T2DM at increased risk for vascular complications. It 
is reported that 26.1% of T2DM patients in Shanghai have albuminuria [R16-4560]. 
Therefore, T2DM management in older patients should be driven by strategies for effective 
and safe treatment aiming to reduce risk of chronic vascular complications of T2DM, as well 
as for improving or maintaining functional status and quality of life. The high burden of 
T2DM treatment in older patients and the associated adverse outcomes result in high health-
care costs to both public and private payers.
Due to the lack of a large-scale, nationwide and systematically conducted survey, there are 
very limited data available on the characteristics and treatment patterns of older patients with 
T2DM in China. Furthermore, no data are available from patients with both T2DM and 
albuminuria in China. This makes it difficult for clinicians to effectively make medical 
decisions for patients with a variety of risk factors and complications, for healthcare 
professionals to assess the unmet medical needs and for healthcare organizations to assess the 
quality of patient care. 
This study will help to better understand the current anti-hyperglycaemic treatment patterns, 
level of glucose control and unmet medical needs in older population of T2DM patients with 
or without albuminuria in China. In addition, it may improve the public awareness on anti-
hyperglycaemic treatment, and provide evidence and direction for improving clinical 
practice. 

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8.
RESEARCH QUESTION AND OBJECTIVES
The present study is to be conducted in older (≥60 years old) outpatients with T2DM in 
hospitals of China.
The primary objective is:

to assess the level of blood glucose, measured by the proportion of patients attaining the 
blood glucose control target defined as HbA1c<7%.
The secondary objectives are:

to investigate the anti-hyperglycaemic treatment patterns of the study population.

to investigate occurrence of the hypoglycaemia and hypoglycaemia leading to therapy
change.

to investigate the anti-hypertension/Lipid Lowering/anti-platelet treatment patterns of the 
study population.

to investigate treatment adherence(follow up duration) to Chinese T2DM guideline 2013

to investigate the clinical characteristics of the study population.

to investigate clinical characteristics, anti-hyperglycaemic treatment pattern and blood 
glucose control in older T2DM patients with albuminuria.

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9.
RESEARCH METHODS
9.1
STUDY DESIGN
This is a multi-centre, cross-sectional, non-interventional study assessing blood glucose target 
attainment, anti-hyperglycaemic treatment pattern and the clinical characteristics in older 
outpatients with T2DM in hospitals of China. This study is designed to collect information of 
older T2DM patients in a real life setting. The primary outcome of this study is the proportion 
of patients attaining blood glucose control target defined as HbA1c<7%. Demographic,
clinical characteristics and treatment patterns of the study population will also be investigated. 
The primary method to be used is descriptive analysis.
9.2
SETTING
9.2.1
Study population
In this cross-sectional study, approximately 1500 patients will be recruited. Older outpatients 
with T2DM will be selected consecutively from departments of endocrinology in at least 30 
hospitals of China.
Figure 1 – Study Flow of the cross-sectional study
Inclusion criteria
•
Patient should fully know and understand the content of consent form, and the 
patient is willing and able to sign an informed consent form
•
Outpatient with confirmed T2DM (According to Definition and Diagnosis 
Diabetes Mellitus :World Health Organization 1999[R04-1142] )
•
Age≥60 years
Exclusion criteria
•
Patients with type 1 diabetes mellitus or secondary DM
•
Patients who are participating in any other clinical study, including any 
questionnaire-based study, any interventional study (including diet/counselling 

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based intervention), or any clinical study in which any medications (including 
Chinese herbal medications) are administered
9.2.2
Visit schedule
Patients will be recruited into the study in the order of their clinical visits scheduled. First 
7 consented and suitable patients will be recruited for each site on each day, or fewer if 
without enough patients. One study visit is planned for each patient. Clinical assessments will 
be performed as part of routine clinical practice. Some laboratory tests results prior to the 
study can be used as source data as specified below. All data required should be entered into 
the Electronic Data Capture (EDC) System only after each patient has consented to 
participation.
During the study visit, the following procedures will be performed:

Signature of informed consent and recording of the date informed consent was given

Determination of eligibility by checking the inclusion/exclusion criteria

Collect the following information
o
Demographic information
o
Personal health history 

Diabetes Mellitus history

Chronic Kidney Disease history

Anti-Hypertension therapy history

Lipid Lowering therapy history

Anti-Platelet therapy history

hypoglycaemic history
o
Family health history (e.g., diabetes, hypertension, and Chronic kidney 
diseases)
o
Lifestyle
o
Physical examination 

body weight

height

waist circumference
o
Vital sign

blood pressure 

heart rate
o
Laboratory tests

HbA1c

Albuminuria

Urine WBC

Fasting plasma glucose (FPG), (examined within one month prior to 
the visit)

Serum creatinine (SCr), uric acid (UA), high density lipoprotein 
cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), 
triglyceride (TG), total cholesterol (TC) (If examined within three 
months prior to the visit，record the result; if examined without  three 

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months prior to visit, record the date of last examination and re-
examine by investigator’s judgment.)
All of the laboratory tests will be performed by local laboratory and will be required on the 
same day of visit. The laboratory tests performed prior to the visit which can be used as 
source data are specified above.
Albuminuria can be measured in a random spot urine sample, a 24-h urine sample, or a timed 
urine sample. The results of albuminuria measurement will be categorized as normal, micro-
and macro-albuminuria based on the definition in Table_1.
Table 1 Definition of Albuminuria
Urinary 
albumin 
excretion 
Random spot urine
24-h urine
timed urine
ACR (mg/g)
24h UAE (mg/24h)
UAE (µg/min)
Normal
<30
<30
<20
Micro-albuminuria
30-300
30-300
20-200
Macro-albuminuria
>300
>300
>200
ACR: albumin-to-creatinine ratio; UAE: urinary albumin excretion
A log of all patients included in the study (i.e. having given informed consent) will be 
maintained in the Investigator Site File (ISF) at the investigational site.
Boehringer Ingelheim reserves the right to discontinue the study overall or at a particular 
study site at any time for the following reasons:
1. Failure to meet expected enrolment goals overall or at a particular study site.
2. Emergence of any efficacy/safety information that could significantly affect continuation 
of the study, or any other administrative reasons.
3. Violation of Good Clinical Practice (GCP), the study protocol, or the contract by a study 
site or investigator, disturbing the appropriate conduct of the study.
The investigator / the study site will be reimbursed for reasonable expenses incurred in case 
of study termination (except in case of the third reason).
9.3
VARIABLES
9.3.1
Primary outcome
The primary outcome is the proportion of patients attaining blood glucose control target 
defined as HbA1c<7%, according to 2015 American Diabetes Association (ADA) [R16-1532]
and 2013 Chinese Diabetes Society (CDS) guidelines.
9.3.2
Secondary outcomes
Secondary outcomes are:

Renal function of patients

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o
Estimated glomerular filtration rate (eGFR) evaluated by CKD Epidemiology 
Collaboration (CKD-EPI) equation expressed as:
GFR = 141 × min(SCr/κ,1)α × max(SCr/κ,1)-1.209 × 0.993Age × 1.018 [if female] × 
1.159 [if black]
If SCr is in mg/dL, κ = 0.7 if female, κ = 0.9 if male
If SCr is in µmol/L, κ = 61.9 if female, κ = 79.6 if male
α = -0.329 if female
α = -0.411 if male
min = the minimum of Scr/κ or 1
max = the maximum of Scr/κ or 1
o
Albuminuria categorized as micro-albuminuria and macro-albuminuria according to 
the definition in Table 1.

Treatment regimens for T2DM that the patients are currently taking, categorized as
follow: (GLP-1 has been regard as OAD  even though it’s an injection treatment)
o
No treatment
o
Only diet control and exercise
o
Oral antidiabetic drug (OAD)-Mono therapy

Biguanide

α-glucosidase inhibitor

Sulfonylureas

Thiazolidinediones

Meglitindes

Dipeptidyl peptidase-4 (DPP-4) inhibitors

Sodium-glucose co-transporter (SGLT-2) inhibitors

Glucagon like peptide-1 (GLP-1) analogue
o
OAD-Combined therapy

Dual

Triple
o
Insulin only
o
OAD + Insulin

Proportion of macro-vascular and micro-vascular diabetic complications:
o
Cardiovascular disease (i.e., coronary artery disease)
o
Cerebrovascular disease (i.e., ischemic stroke)
o
Peripheral vascular disease (i.e., diabetic foot)
o
Kidney disease (i.e., diabetes nephropathy)
o
Retinopathy 
o
Neuropathy 

Proportion of Hypoglycaemic occurrence

Proportion of Hypoglycaemia leading to therapy change

Proportion of Anti-hypertension therapy usage

Proportion of Lipid Lowering therapy usage

Proportion of Anti-Platelet therapy usage

Treatment adherence to Chinese T2DM guideline 2013

0-3 month

3-6 month

6-12 month

>12 month

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9.3.4
Safety events
All adverse drug reactions (ADRs) (serious and non-serious) and all AEs with fatal outcome
(death) must be collected by the investigator from signing the informed consent onwards
until the end of the study.
9.4
DATA SOURCES
Data will be newly collected from the patient by the investigator and recorded as source data
at the site, i.e. the physician’s records, and entered in the eCRF by the investigator or site
staff.
9.5
STUDY SIZE
According to a recent study, the proportion of patients with diabetes in China who achieved a 
target blood glucose level of HbA1c <7% was 39.8% in patients aged 60-69 years old and 
38.9% in patients aged 70 years old or above [1]. It is assumed that the proportion of patients 

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attaining the target blood glucose level in the present study will be 39%. To ensure the 
accuracy of the estimate for proportion of patients with HbA1c <7%, the length of a two-sided 
95% confidence interval (CI) should not extend beyond 5%. A sample size of 1463 patients is 
required to achieve the expected accuracy. Assuming HbA1c measurements are available for 
97.5% of the enrolled patients, a total of 1500 patients will be recruited.
9.6
DATA MANAGEMENT
All data generated by the site personnel will be captured electronically at each study centre
using eCRFs. Data from external sources (such as laboratory data) will be imported into the 
database.
In order to maintain source documentation of the outpatient record, Investigators will have 
complete access to the data for their patients, thus facilitating quality improvement initiatives 
and single-centre research. Each investigator will be required to first report all patient data on 
the outpatient medical chart or other acceptable original medical record.
Local Clinical Research Associate (CRA) will conduct routine on-site monitoring of the 
original data quality and review the study material and data.
Data queries generated from the database will be created on an ongoing basis; queries will be 
based on the data management system logic deck and database validation for adequacy and 
consistency.
9.7
DATA ANALYSIS
All the following analyses are exploratory in nature and the p-values provided by these 
analyses will only be nominal. Missing data will not be imputed. Details of all analyses will 
be provided in the statistical and epidemiological analysis plan (SEAP).
9.7.1
Analysis population
The statistical analysis will be based on the following populations.
Full Analysis Set (FAS)
The FAS includes all patients with an HbA1c measurement.
FAS – Albuminuria
The FAS – Albuminuria dataset is a subset of patients of FAS, which includes T2DM patients
with albuminuria (micro-albuminuria without urinary tract infection based on urine WBC 
result and macro- albuminuria).
9.7.2
Primary analyses
The proportion of patients attaining blood glucose control target of HbA1c<7% will be 
summarized descriptively on FAS.
 
Detailed information about variable categorization will be specified in SEAP.

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9.7.3
Secondary analyses
 
The analyses for following secondary outcomes will be performed on both FAS and 
FAS - Albuminuria as below:

For renal function variables, eGFR and albuminuria, descriptive statistics will be 
calculated 
 

The treatment pattern for T2DM will be summarized descriptively with frequency and 
proportion, 

The proportion of the occurrence of hypoglycaemia and the proportion of hypoglycaemia 
leading to therapy change will be summarized descriptively.
Then for the other secondary outcomes, the analyses will only be performed on FAS:

The proportion of each macro vascular and micro-vascular diabetic complications will be 
calculated.

The proportion of using anti-hypertension therapy, lipid –lowering therapy, and anti-
platelet therapy will be calculated respectively.

The treatment adherence will be summarized using the proportion of each follow-up 
duration category.
9.8
QUALITY CONTROL
Once the eCRF clinical data have been submitted to the central server at the independent data 
centre, corrections to the data fields will be captured in an audit trail. The reason for change, 
the name of the person who performed the change, together with the time and date will be 
logged to provide an audit trail. 
If additional corrections are needed, the responsible monitor or data manager will raise a 
query in the EDC application. The appropriate staff at the study site will answer queries sent 
to the investigator. The name of the staff member responding to the query, and time and date 
stamp will be captured to provide an audit trail. Once all source data verification is complete 
and all queries are closed, the monitor will freeze the eCRF page.
The specific procedures to be used for data entry and query resolution using the EDC 
system/eCRF will be provided to study sites in a training manual. In addition, site personnel 
will receive training on the EDC system/eCRF.

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All the laboratory tests will be conducted in the qualified local clinical laboratory.
9.9
LIMITATIONS OF THE RESEARCH METHODS
Some limitations are unavoidable given the design of this cross-sectional study; however, this 
study will generate substantial new knowledge that applies to the real-world clinical setting.
Secondly, due to cross-sectional nature of our study, there may be potential reverse causation 
bias. Therefore the data need to be interpreted with cautions.
A further limitation of the study is that albuminuria is estimated based on a single 
measurement. Hence, no data on the reproducibility of the urinary albumin excretion 
measurements will be available. Moreover, the data regarding HbA1c will have to be 
interpreted with caution as blood measurement are not performed at central laboratory.
9.10
OTHER ASPECTS
9.10.1
Study compliance, data protection and study result
The study will be carried out in compliance with the protocol, the principles laid down in the 
Declaration of Helsinki, in accordance with the International Conference on Harmonisation 
(ICH) Harmonised Tripartite Guideline for GCP and relevant Boehringer Ingelheim Standard 
Operating Procedures (SOPs). Standard medical care (prophylactic, diagnostic and 
therapeutic procedures) remains in the responsibility of the treating physician of the patient.
The investigator should inform the sponsor immediately of any urgent safety measures taken 
to protect the study subjects against any immediate hazard, and also of any serious breaches 
of the protocol/ICH GCP.
The rights of the investigator and of the sponsor with regard to publication of the results of 
this trial are described in the investigator contract. As a general rule, no trial results should be 
published prior to finalisation of the Study Report.
9.10.2
Study approval, patient information and informed consent
This study will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB) / Independent Ethics Committee 
(IEC) and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments.
Prior to patient participation in the study, written informed consent must be obtained from 
each patient (or the patient’s legally accepted representative) according to ICH GCP and to 
the regulatory and legal requirements of China. Each signature must be personally dated by 
each signatory and the informed consent and any additional patient-information form retained 
by the investigator as part of the study records. A signed copy of the informed consent and 
any additional patient information must be given to each patient or the patient’s legally 
accepted representative.

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The patient must be informed that his/her personal study-related data will be used by 
Boehringer Ingelheim in accordance with the local data protection law. The level of 
disclosure must also be explained to the patient.
The patient must be informed that his / her medical records may be examined by authorised 
monitors (Local Clinical Monitor /CRA) or Clinical Quality Assurance auditors appointed by 
Boehringer Ingelheim, by appropriate IRB / IEC members, and by inspectors from regulatory 
authorities.
9.10.3
Data quality assurance
A quality assurance audit/inspection of this study may be conducted by the sponsor or 
sponsor’s designees or by IRBs/IECs or by regulatory authorities. The quality assurance 
auditor will have access to all medical records, the investigator’s study-related files and 
correspondence, and the informed consent documentation of this study.
9.10.4
Study records
Case Report Forms (CRFs) for individual patients will be provided by the sponsor via remote 
data capture. 
9.10.4.1
Source documents
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents include laboratory test report outpatient 
medical chart, e-outpatient medical chart and other original medical record. Source 
documents are filed at the investigator’s site.
Data entered in the eCRFs that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may need 
to request previous medical records or transfer records, depending on the trial; also current 
medical records must be available.
For eCRFs, all data must be derived from source documents.
9.10.4.2
Direct access to source data and documents
The investigator / institution will permit study-related monitoring, audits, IRB / IEC review 
and regulatory inspection, providing direct access to all related source data / documents. 
eCRFs and all source documents, including progress notes and copies of laboratory and 
medical test results must be available at all times for review by the sponsor’s clinical study 
monitor, auditor and inspection by health authorities (e.g. Food and Drug Administration 
[FDA]). The CRA / on-site monitor and auditor may review all eCRFs, and written informed 
consents. The accuracy of the data will be verified by reviewing the documents described in 
Section 9.10.4.1.

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9.10.4.3
Statement of confidentiality
Individual patient medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited with the exceptions noted below. 
Patient confidentiality will be ensured by using patient identification code numbers.
Data generated as a result of the study need to be available for inspection on request by the 
participating physicians, the sponsor’s representatives, by the IRB / IEC and the regulatory 
authorities.

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10.
PROTECTION OF HUMAN SUBJECTS
The procedures set out in this study protocol are designed to ensure that the sponsor and 
investigator 
abide 
by 
the 
principles 
of 
the 
International 
Society 
for 
Good 
Pharmacoepidemiology Practices (GPP) guidelines [R09-0182]. The study also will be 
carried out in keeping with local legal requirements.

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11.
MANAGEMENT 
AND 
REPORTING 
OF 
ADVERSE 
EVENTS/ADVERSE REACTIONS
11.1
DEFINITIONS OF ADVERSE EVENTS
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a medicinal product and which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavourable and 
unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.
Adverse reaction
An adverse reaction is defined as a response to a medicinal product which is noxious and 
unintended. Response in this context means that a causal relationship between a medicinal 
product and an AE is at least a reasonable possibility. Adverse reactions may arise from use 
of the product within or outside the terms of the marketing authorisation or from occupational 
exposure. Conditions of use outside the marketing authorisation include off-label use, 
overdose, misuse, abuse and medication errors.
Serious adverse event
A serious adverse event (SAE) is defined as any AE which
-
results in death, 
-
is life-threatening, 
-
requires in-patient hospitalization, or
-
prolongation of existing hospitalization, 
-
results in persistent or significant disability or incapacity, or 
-
is a congenital anomaly/birth defect 
Life-threatening in this context refers to a reaction in which the patient was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused 
death if more severe.
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life-threatening or result in death or hospitalization but might jeopardise the 
patient or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or 
development of dependency or abuse. Any suspected transmission via a medicinal product of 
an infectious agent is also considered a serious adverse reaction.
Adverse Event of Special Interest (AESI)
The term AESI relates to any specific AE that has been identified at the project level as being 
of particular concern for prospective safety monitoring and safety assessment within this 

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study, e.g. the potential for AEs based on knowledge from other compounds in the same 
class. 
No AESIs have been defined for this study.
11.2
ADVERSE REACTION AND FATAL ADVERSE EVENT REPORTING
The investigator shall maintain and keep detailed records of all AEs in their patient files.
Collection of AEs
The study design is of non-interventional nature and the study is conducted within the 
conditions of the approved marketing authorisation. Sufficient data from controlled 
interventional trials are available to support the evidence on the safety and efficacy of the 
studied BI drug. For this reason the following AE collection and reporting requirements have 
been defined.
The following must be collected by the investigator in the (e)CRF from signing the informed 
consent onwards until the end of the study for any BI drug approved for the indication of 
T2DM
-
all ADRs (serious and non-serious), 
-
all AEs with fatal outcome (death).
All ADRs, including those persisting after study completion must be followed up until they 
are resolved, have been sufficiently characterized, or no further information can be obtained.
The investigator carefully assesses whether an AE constitutes an ADR using the information 
below. 
Causal relationship of adverse event
The definition of an adverse reaction implies at least a reasonable possibility of a causal 
relationship between a suspected medicinal product and an adverse event. An adverse 
reaction, in contrast to an adverse event, is characterized by the fact that a causal relationship 
between a medicinal product and an occurrence is suspected. 
Medical judgment should be used to determine the relationship, considering all relevant 
factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, 
confounding factors such as concomitant medication, concomitant diseases and relevant 
history.
Arguments that may suggest a reasonable causal relationship could be:
•
The event is consistent with the known pharmacology of the drug.
•
The event is known to be caused by or attributed to the drug class.
•
A plausible time to onset of the event relative to the time of drug exposure.
•
Evidence that the event is reproducible when the drug is re-introduced.
•
No medically sound alternative etiologies that could explain the event (e.g. 
preexisting or concomitant diseases, or co-medications).
•
The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g. Stevens-Johnson syndrome).

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•
An indication of dose-response (i.e. greater effect size if the dose is increased, smaller 
effect size if dose is diminished).
Arguments that may suggest that there is no reasonable possibility of a causal relationship 
could be:
•
No plausible time to onset of the event relative to the time of drug exposure is evident 
(e.g. pre-treatment cases, diagnosis of cancer or chronic disease within days/weeks of 
drug administration; an allergic reaction weeks after discontinuation of the drug 
concerned)
•
Continuation of the event despite the withdrawal of the medication, taking into 
account the pharmacological properties of the compound (e.g. after 5 half-lives).
Of note, this criterion may not be applicable to events whose time course is prolonged 
despite removing the original trigger.
•
Additional arguments amongst those stated before, like alternative explanation (e.g. 
situations where other drugs or underlying diseases appear to provide a more likely 
explanation for the observed event than the drug concerned).
•
Disappearance of the event even though the study drug treatment continues or remains 
unchanged.
Intensity of adverse event
The intensity of the AE should be judged based on the following:
Mild:
Awareness of sign(s) or symptom(s) which is/are easily tolerated
Moderate:
Enough discomfort to cause interference with usual activity
Severe:
Incapacitating or causing inability to work or to perform usual activities
Pregnancy:
In rare cases, pregnancy might occur in a study. Once a subject has been enrolled into the 
study, after having taken any BI drug approved for the indication of T2DM, the investigator 
must report any drug exposure during pregnancy, which occurred in a female subject or in a 
partner to a male subject to the sponsor by means of Part A of the Pregnancy Monitoring 
Form. The outcome of the pregnancy associated with the drug exposure during pregnancy 
must be followed up and reported by means of Part B of the Pregnancy Monitoring Form. 
In the absence of a reportable AE, only the Pregnancy Monitoring Form must be completed, 
otherwise the NIS AE form is to be completed and forwarded as well within the respective 
timelines. 
Expedited Reporting of AEs and Drug Exposure during Pregnancy (DEDP)
The following must be reported by the investigator on the NIS AE form from signing the 
informed consent onwards until the end of the study:
Type of Report
Timeline
All Serious ADRs (SADRs) associated with 
the any BI drug approved for the indication 
of T2DM
immediately within 24 hours
All AEs with fatal outcome in patients 
exposed to any BI drug approved for the 
indication of T2DM
immediately within 24 hours

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All non-serious ADRs associated with the 
any BI drug approved for the indication of 
T2DM
7 calendar days
All 
pregnancy 
monitoring
forms
concerning DEDP to any BI drug approved 
for the indication T2DM
7 calendar days
The same timelines apply if follow-up information becomes available for the respective 
events. In specific occasions the Investigator could inform the sponsor upfront via telephone. 
This does not replace the requirement to complete and fax the NIS AE form.
Information required
For each reportable adverse event, the investigator should provide the information requested 
on the appropriate (e)CRF pages and the NIS AE form.
Reporting of related Adverse Events associated with any other BI drug
The investigator is encouraged to report all adverse events related to any BI drug other than 
the BI drug approved for the indication of T2DM according to the local regulatory 
requirements for spontaneous AE reporting at the investigator’s discretion by using the 
locally established routes and AE report forms. The term AE includes drug exposure during 
pregnancy, and, regardless of whether an AE occurred or not, any abuse, off-label use, 
misuse, medication error, occupational exposure, lack of effect, and unexpected benefit.
11.3
REPORTING TO HEALTH AUTHORITIES
Adverse event reporting to regulatory agencies will be done by the marketing authorisation 
holder (MAH) according to local and international regulatory requirements.

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12.
PLANS FOR DISSEMINATING AND COMMUNICATING 
STUDY RESULTS
By signing the study protocol, the investigator agrees with the use of results of the study for 
the purposes of national and international registration, publication and information for 
medical and pharmaceutical professionals. If necessary, the authorities will be notified of the 
investigator's name, address, qualifications and extent of involvement.
An investigator shall not publish any data (poster, abstract, paper, etc.) without having 
consulted with the sponsor in advance.
The results obtained within the study are the exclusive property of the sponsor. After 
validation, the results will be shared with the investigators of the study. The sponsor 
recognizes the ethical obligation to disseminate findings of potential scientific or public 
health importance (e.g., results pertaining to the safety of a marketed medication). Study 
results will be included in abstracts sent to scientific congresses and articles sent to scientific 
reviews. Specific plans for disseminating and communicating the study results will be 
produced when the results are available. 
Results of this non-interventional study will be disclosed on encepp.eu and clinicaltrials.gov 
and a study specific publication plan will be developed to describe planned publications.

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13.
REFERENCES
13.1
PUBLISHED REFERENCES
R14-1806
International Diabetes Federation. IDF Diabetes Atlas. 6th ed. Brussels, 
Belgium: International Diabetes Federation; 2013.
R13-5351
Xu Y, Wang LM, He J, Bi YF, Li M, Wang TG, et al. Prevalence and control 
of diabetes in Chinese adults JAMA. 2013; 310: 948-959
R16-4557
Ji LN, Lu JM, Guo XH, Yang WY, Weng JP, Jia WP, et al. Glycemic control 
among patients in China with type 2 diabetes mellitus receiving oral drugs or 
injectables. BMC Public Health. 2013; 13: 602
P16-10791
Dardano A, Penno G, Del Prato S, Miccoli R. Optimal therapy of type 2 
diabetes: a controversial challenge. Aging (Albany NY). 2014; 6: 187-206.
P13-17218
Kountz D. The dipeptidyl peptidase (DPP)-4 inhibitors for type 2 diabetes 
mellitus in challenging patient groups. Adv Ther. 2013; 30: 1067-1085
R16-4558
Bramlage P, Gitt AK, Binz C, Krekler M, Deeg E, Tschope D. Oral 
antidiabetic treatment in type-2 diabetes in the elderly: balancing the need for 
glucose control and the risk of hypoglycemia. Cardiovasc Diabetol. 2012; 11:
122
R16-4559
Huang H, Li H, Zheng FP, Lu WN, Dong XH, Ruan y. Clinical features and 
risk factors of renal damage in elderly and non-elderly patients with type 2 
diabetes mellitus. Zhonghua Yi Xue Za Zhi. 2010; 90:967-971
R16-4560
Lu B, Song XY, Dong XH, Yang YH, Zhang ZY, Wen J, etc. High prevalence 
of chronic kidney disease in population-based patients diagnosed with type 2 
diabetes in downtown Shanghai. J Diabetes Complications. 2008; 22: 96-103
R16-1532     Standards of medical care in diabetes--2015: summary of revisions. Diabetes 
Care. 2015;38 Suppl:S4.
R04-1142
Definition, diagnosis and classification of diabetes mellitus and its 
complications: report of a WHO consultation. Part 1: diagnosis and 
classification 
of 
diabetes 
mellitus. 
WHO/NCD/NCS/99.2. 
Geneva: 
WorldHealth Organization, Department of Noncommunicable Disease 
Surveillance, , 1 - 59 (1999)
R09-0182
International Society for Pharmacoepidemiology (ISPE). Guidelines for good 
pharmacoepidemiology practices (GPP). Pharmacoepidemiol Drug Saf. 2008;
17: 200-208.
13.2
UNPUBLISHED REFERENCES
None

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Non-interventional Study Protocol                                                                 20 Dec 2016
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ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
None

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Non-interventional Study Protocol                                                                 20 Dec 2016
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European Network of Centres for 
Pharmacoepidemiology and 
Pharmacovigilance
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS
Doc.Ref. EMA/540136/2009 
ENCePP Checklist for Study Protocols (Revision 3)
Adopted by the ENCePP Steering Group on 01/07/2016
The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP)
welcomes innovative designs and new methods of research. This Checklist has been developed by 
ENCePP to stimulate consideration of important principles when designing and writing a 
pharmacoepidemiological or pharmacovigilance study protocol. The Checklist is intended to 
promote the quality of such studies, not their uniformity. The user is also referred to the ENCePP 
Guide on Methodological Standards in Pharmacoepidemiology, which reviews and gives direct 
electronic access to guidance for research in pharmacoepidemiology and pharmacovigilance.
For each question of the Checklist, the investigator should indicate whether or not it has been 
addressed in the study protocol. If the answer is “Yes”, the section number of the protocol where 
this issue has been discussed should be specified. It is possible that some questions do not apply
to a particular study (for example, in the case of an innovative study design). In this case, the 
answer ‘N/A’ (Not Applicable) can be checked and the “Comments” field included for each section 
should be used to explain why. The “Comments” field can also be used to elaborate on a “No” 
answer. 
This Checklist should be included as an Annex by marketing authorisation holders when submitting 
the protocol of a non-interventional post-authorisation safety study (PASS) to a regulatory 
authority (see the Guidance on the format and content of the protocol of non-interventional post-
authorisation safety studies). The Checklist is a supporting document and does not replace the 
format of the protocol for PASS as recommended in the Guidance and Module VIII of the Good 
pharmacovigilance practices (GVP).
Study title:
Clinical characteristics, anti-hyperglycaemic treatment pattern and target 
attainment of type 2 diabetes mellitus patients in older population with or 
without albuminuria in China: A nationwide cross-sectional study
Study reference number:
1218.174
Section 1: Milestones
Yes
No
N/A
Section
Number
1.1
Does the protocol specify timelines for 
1.1.1 Start of data collection1
1.1.2 End of data collection2
4
                                                
1 Date from which information on the first study is first recorded in the study dataset or, in the case of 
secondary use of data, the date from which data extraction starts.

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Section 1: Milestones
Yes
No
N/A
Section
Number
1.1.3 Study progress report(s)
1.1.4 Interim progress report(s)
1.1.5 Registration in the EU PAS register
1.1.6 Final report of study results.
Comments:
Total recruitment period is 7 months, no progress report was set in this NIS. And this 
study is conducted in China Mainland only, not in Europe.
Section 2: Research question
Yes
No
N/
A
Section
Number
2.1
Does the formulation of the research question 
and objectives clearly explain: 
2.1.1 Why the study is conducted? (e.g. to address 
an important public health concern, a risk identified in 
the risk management plan, an emerging safety issue)
8,9.2.1
2.1.2 The objective(s) of the study?
2.1.3
The target population?
(i.e. population or 
subgroup to whom the study results are intended to be 
generalised)
2.1.4
Which hypothesis(-es) is (are) to be 
tested?
2.1.5 If applicable, that there is no a priori
hypothesis?
Comments:
This is a cross-sectional non-interventional study based on newly collected data. All the 
analyses will be descriptive, and no hypothesis testing was set.
Section 3: Study design
Yes
No
N/
A
Section 
Number
3.1
Is the study design described? (e.g. cohort, case-
control, cross-sectional, new or alternative design) 
9.1
3.2
Does the protocol specify whether the study is 
based on primary, secondary or combined data 
collection?
9.1
3.3
Does 
the 
protocol 
specify 
measures 
of
occurrence? (e.g. incidence rate, absolute risk)
7
3.4
Does 
the 
protocol 
specify
measure(s) 
of 
association? (e.g. relative risk, odds ratio, excess risk, 
incidence rate ratio, hazard ratio, number needed to harm 
(NNH) per year)
7
                                                                                                                                                       
2 Date from which the analytical dataset is completely available.

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Section 3: Study design
Yes
No
N/
A
Section 
Number
3.5
Does the protocol describe the approach for the 
collection 
and 
reporting 
of 
adverse 
events/adverse reactions? (e.g. adverse events that 
will not be collected in case of primary data collection)
11
Comments:
Section 4: Source and study populations
Yes
No
N/A
Section 
Number
4.1
Is the source population described?
9.2.1
4.2
Is the planned study population defined in terms 
of:
4.2.1 Study time period?
4.2.2 Age and sex?
9.2.1
4.2.3 Country of origin?
4.2.4 Disease/indication?
4.2.5 Duration of follow-up?
4.3
Does 
the 
protocol 
define 
how 
the 
study 
population will be sampled from the source 
population? (e.g. event or inclusion/exclusion criteria)
9.2.1
Comments:
Section 5: Exposure definition and measurement
Yes
No
N/
A
Section
Number
5.1
Does the protocol describe how the study 
exposure 
is 
defined 
and 
measured?
(e.g. operational 
details 
for 
defining 
and 
categorising 
exposure, measurement of dose and duration of drug 
exposure)
5.2
Does the protocol address the validity of the 
exposure measurement? (e.g. precision, accuracy, use 
of validation sub-study)
5.3
Is 
exposure 
classified 
according 
to 
time 
windows? (e.g. current user, former user, non-use)
5.4
Is 
exposure 
classified 
based 
on 
biological 
mechanism of action and taking into account the 
pharmacokinetics and pharmacodynamics of the 
drug?
Comments:
This is a cross-sectional non-interventional study based on newly collected data. All the 
analyses will be descriptive. We will not study the effects of drug exposure.

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Non-interventional Study Protocol                                                                 20 Dec 2016
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Section 6: Outcome definition and measurement
Yes
No
N/
A
Section 
Number
6.1
Does the protocol specify the primary and 
secondary 
(if 
applicable) 
outcome(s) 
to 
be 
investigated?
9.3
6.2
Does the protocol describe how the outcomes
are defined and measured? 
9.3
6.3
Does the protocol address
the validity of 
outcome
measurement? 
(e.g. precision, 
accuracy, 
sensitivity, specificity, positive predictive value, prospective 
or retrospective ascertainment, use of validation sub-study)
9.3
6.4
Does the protocol describe specific endpoints 
relevant for Health Technology Assessment? 
(e.g. HRQoL, QALYs, DALYS, health care services utilisation, 
burden of disease, disease management)
Comments:
This Non-interventional study is a New Data Collection study of the T2DM of Old patient. 
There is not any Health Technology Assessment collected and the study outcomes are 
not relevant for Health Technology Assessment.
Section 7: Bias
Yes
No
N/
A
Section
Number
7.1
Does the protocol describe how confounding will 
be addressed in the study?
9.7
7.1.1. Does the protocol address confounding by 
indication if applicable?
7.2
Does the protocol address:
7.2.1. Selection biases (e.g. healthy user bias)
9.2.2
7.2.2. Information biases (e.g. misclassification of 
exposure and endpoints, time-related bias)
9.2.2
7.3
Does the protocol address the validity of the 
study covariates?
Comments:
This is a cross-sectional non-interventional study based on newly collected data. All the 
analyses will be descriptive. Therefore, there will not be confounding by indication in the 
study. All the data will be newly collected so we are not planning to validate the study 
covariates.
Section 8: Effect modification
Yes
No
N/
A
Section
Number
8.1
Does the protocol address effect modifiers?
(e.g. collection of data on known effect modifiers, sub-group 
analyses, anticipated direction of effect) 
Comments:
This is a cross-sectional non-interventional study based on newly collected data. All the 
analyses will be descriptive. Therefore, we will not examine effect modifiers.

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Section 9: Data sources
Yes
No
N/A
Section 
Number
9.1
Does the protocol describe the data source(s) 
used in the study for the ascertainment of:
9.1.1 Exposure?
(e.g. pharmacy dispensing, general 
practice prescribing, claims data, self-report, face-to-face 
interview)
9.1.2 
Outcomes?
(e.g. clinical 
records, 
laboratory 
markers or values, claims data, self-report, patient 
interview including scales and questionnaires, vital 
statistics)
9.1.3 Covariates?
9.2
Does the protocol describe the information 
available from the data source(s) on:
9.2.1 Exposure? (e.g. date of dispensing, drug quantity, 
dose,  number of days of supply prescription, daily 
dosage,  prescriber)
9.2.2 Outcomes?
(e.g. date of occurrence, multiple 
event, severity measures related to event)
9.2.3 Covariates? (e.g. age, sex, clinical and drug use 
history, co-morbidity, co-medications, lifestyle)
9.3
Is a coding system described for: 
9.3.1 Exposure? (e.g. WHO Drug Dictionary, Anatomical 
Therapeutic Chemical (ATC) Classification System)
9.3.2
Outcomes?
(e.g. International Classification of 
Diseases (ICD)-10, Medical Dictionary for Regulatory 
Activities (MedDRA))
9.3.3 Covariates?
9.4
Is a linkage method between data sources 
described? (e.g. based on a unique identifier or other)
Comments:
This is a non-interventional study based on newly collected data. We will not use existing 
data sources.
Section 10: Analysis plan
Yes
No
N/
A
Section
Number
10.1 Is the choice of statistical techniques described? 
9.7
10.2 Are descriptive analyses included?
9.7
10.3 Are stratified analyses included?
9.7
10.4 Does the plan describe methods for adjusting for 
confounding?
9.7
10.5 Does the plan describe methods for handling 
missing data?
9.7
10.6 Is 
sample 
size 
and/or 
statistical 
power 
estimated?
9.5
Comments:

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Non-interventional Study Protocol                                                                 20 Dec 2016
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Section 
11: 
Data 
management 
and 
quality 
control
Yes
No
N/
A
Section
Number
11.1 Does the protocol provide information on data 
storage?
(e.g. software and IT environment, database 
maintenance and anti-fraud protection, archiving)
9.8
11.2 Are methods of quality assurance described?
9.8
11.3 Is there a
system in place for independent 
review of study results? 
Comments:
This study is non-interventional study for real word data. The study result will reflect the 
real world situation, so no independent review for study result was conducted.
Section 12: Limitations
Yes
No
N/
A
Section
Number
12.1 Does the protocol discuss the impact on the 
study results of:
12.1.1 Selection bias?
9.9
12.1.2 Information bias?
12.1.3
Residual/unmeasured 
confounding?
(e.g. anticipated direction and magnitude of such biases, 
validation sub-study, use of validation and external data, 
analytical methods)
12.2 Does the protocol discuss study feasibility?
(e.g. study size, anticipated exposure, duration of follow-up 
in a cohort study, patient recruitment)
9.9
Comments:
This Non-interventional Study is a cross-section and descriptive analysis study. 
Section 13: Ethical issues
Yes
No
N/
A
Section
Number
13.1 Have 
requirements 
of 
Ethics 
Committee/ 
Institutional Review Board been described?
9.10
13.2 Has any outcome of an ethical review procedure 
been addressed?
9.10
13.3 Have 
data 
protection 
requirements 
been 
described?
9.10
Comments:
Section 14: Amendments and deviations
Yes
No
N/
A
Section
Number
14.1 Does the protocol include a section to document 
amendments and deviations? 
5

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Non-interventional Study Protocol                                                                 20 Dec 2016
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Comments:
Section 15: Plans for communication of study 
results
Yes
No
N/
A
Section
Number
15.1 Are plans described for communicating study 
results (e.g. to regulatory authorities)?
12
15.2 Are plans described for disseminating
study 
results externally, including publication?
Comments:
There will be an independent publication plan. 
Name of the main author of the protocol:
Date: dd/Month/year
Signature: 

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Non-interventional Study Protocol                                                                 20 Dec 2016
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ANNEX 3. ADDITIONAL INFORMATION
None

 
 
 
 
APPROVAL / SIGNATURE PAGE 
 
Document Number: 
 
Technical Version Number:
 
Document Name: 
 
 
 
                                                                                                                 
 
Title: 
 
 
 
 
                                                                                                                   
 
Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c14196017
1.0
clinical-trial-protocol-version-2.0
Clinical characteristics, anti-hyperglycaemic treatment pattern and target attainment
of type 2 diabetes mellitus patients in older population with or without albuminuria in
China: A nationwide cross-sectional study
Approval-Trial Clinical Monitor
21 Dec 2016 03:46 CET
Approval-Biostatistics
21 Dec 2016 09:05 CET
Approval-Team Member Medical
Affairs
22 Dec 2016 12:20 CET
Approval-Pharmacovigilance
31 Dec 2016 12:41 CET
Approval-Therapeutic Area 
05 Jan 2017 03:51 CET
Approval-Medical 
05 Jan 2017 03:59 CET

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Document Number: 
 Technical Version Number:
 
 
 
(Continued) Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c14196017
1.0