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Clinical Trial Results:
Efficacy and safety of semaglutide versus dulaglutide as add-on to metformin in subjects with type 2 diabetes

Summary
EudraCT number
 2014-005375-91
Trial protocol
 IE   FI   DE   GB   SK   LV   LT   GR   ES   PT   HR  
Global end of trial date
19 May 2017

Results information
Results version number
 v1(current)
This version publication date
30 May 2018
First version publication date
30 May 2018
Other versions

Trial information

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Trial identification
Sponsor protocol code
NN9535-4216
Additional study identifiers
ISRCTN number
 -
US NCT number
 NCT02648204
WHO universal trial number (UTN)
 U1111-1164-8495
Sponsors
Sponsor organisation name
Novo Nordisk A/S
Sponsor organisation address
Novo Allé, Bagsvaerd, Denmark, 2880
Public contact
Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
Scientific contact
Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)
No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
No
Results analysis stage
Analysis stage
Final
Date of interim/final analysis
30 Nov 2017
Is this the analysis of the primary completion data?
Yes
Primary completion date
10 Apr 2017
Global end of trial reached?
Yes
Global end of trial date
19 May 2017
Was the trial ended prematurely?
No
General information about the trial
Main objective of the trial
o compare the effect of once-weekly dosing of two dose levels of subcutaneous semaglutide (0.5 mg and 1.0 mg) versus once-weekly dosing of two dose levels of subcutaneous dulaglutide (0.75 mg and 1.5 mg) on glycaemic control in subjects with type 2 diabetes on a background treatment with metformin.
Protection of trial subjects
The trial was conducted in accordance with the Declaration of Helsinki, ICH Good Clinical Practice, EN ISO 14155 Parts 1 and 2 and FDA 21 CFR 312.120.
Background therapy
 Subjects were to continue metformin at pre-trial dose and frequency during the whole treatment period unless rescue medication was needed.
Evidence for comparator
 Not applicable
Actual start date of recruitment
06 Jan 2016
Long term follow-up planned
No
Independent data monitoring committee (IDMC) involvement?
No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled
Bulgaria: 60
Country: Number of subjects enrolled
Germany: 58
Country: Number of subjects enrolled
Spain: 63
Country: Number of subjects enrolled
Finland: 31
Country: Number of subjects enrolled
United Kingdom: 70
Country: Number of subjects enrolled
Greece: 73
Country: Number of subjects enrolled
Hong Kong: 30
Country: Number of subjects enrolled
Croatia: 27
Country: Number of subjects enrolled
India: 130
Country: Number of subjects enrolled
Ireland: 22
Country: Number of subjects enrolled
Lithuania: 40
Country: Number of subjects enrolled
Latvia: 35
Country: Number of subjects enrolled
Portugal: 14
Country: Number of subjects enrolled
Romania: 65
Country: Number of subjects enrolled
Slovakia: 40
Country: Number of subjects enrolled
United States: 441
Worldwide total number of subjects
1199
EEA total number of subjects
598
Number of subjects enrolled per age group
In utero
0
Preterm newborn - gestational age
0
Newborns (0-27 days)
0
Infants and toddlers (28 days-23 months)
0
Children (2-11 years)
0
Adolescents (12-17 years)
0
Adults (18-64 years)
939
From 65 to 84 years
260
85 years and over
0

Subject disposition

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Recruitment
Recruitment details
 A total of 210 sites were approved for recruiting subjects, of which 196 sites randomized the subjects: Bulgaria: 6; Croatia: 6; Finland: 6; Germany: 6; Greece: 8; Hong Kong: 1; India: 22; Ireland: 5; Latvia: 3; Lithuania: 5; Portugal: 4; Romania: 7; Slovakia: 6; Spain: 8; United Kingdom: 8; United States: 95.

Pre-assignment
Screening details
 A total of 1201 subjects were randomized in the trial: Semaglutide 0.5 mg-301 subjects, Semaglutide 1.0 mg-300 subjects, Dulaglutide 0.75 mg-300 subjects, Dulaglutide 1.5 mg-300 subjects. Of the 1201 subjects, 1199 were exposed to trial products and 2 randomised subjects withdrew prior to exposure (1 subject in each Dulaglutide arm).

Period 1
Period 1 title
Overall Study (overall period)
Is this the baseline period?
 Yes
Allocation method
Randomised - controlled
Blinding used
 Not blinded
Blinding implementation details
Not applicable

Arms
Are arms mutually exclusive
Yes

Arm title
 Semaglutide 0.5 mg
Arm description
 Subjects received subcutaneous (s.c., under the skin) injections of semaglutide once weekly (OW) for treatment duration of 40 weeks. Subjects received semaglutide 0.25 mg for 4 weeks (weeks 1 to 4) followed by 0.5 mg for 36 weeks (weeks 5 to 40). Subjects were followed for 5 weeks after completion of treatment period.
Arm type
 Experimental

Investigational medicinal product name
Semaglutide B 1.34mg/ml PDS290
Investigational medicinal product code
Other name
Pharmaceutical forms
Solution for injection in pre-filled pen
Routes of administration
Subcutaneous use
Dosage and administration details
Semaglutide solution for injection in pre-filled PDS290 pen-injector, was administered by s.c. injection either in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Arm title
 Semaglutide 1.0 mg
Arm description
 Subjects received s.c. injections of semaglutide OW for treatment duration of 40 weeks. Subjects received semaglutide 0.25 mg for 4 weeks (weeks 1 to 4) followed by 0.5 mg for another 4 weeks (weeks 5 to 8) and then semaglutide 1.0 mg for remaining 32 weeks (weeks 9-40). Subjects were followed for 5 weeks after completion of treatment period.
Arm type
 Experimental

Investigational medicinal product name
Semaglutide B 1.34mg/ml PDS290
Investigational medicinal product code
Other name
Pharmaceutical forms
Solution for injection in pre-filled pen
Routes of administration
Subcutaneous use
Dosage and administration details
Semaglutide solution for injection in pre-filled PDS290 pen-injector, was administered by s.c. injection either in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Arm title
 Dulaglutide 0.75 mg
Arm description
 Subjects received s.c. injections of dulaglutide 0.75 mg OW for treatment duration of 40 weeks. Subjects were followed for 5 weeks after completion of treatment period.
Arm type
 Active comparator

Investigational medicinal product name
Dulaglutide
Investigational medicinal product code
Other name
Trulicity®
Pharmaceutical forms
Solution for injection
Routes of administration
Subcutaneous use
Dosage and administration details
Dulaglutide solution for injection in a pre-filled pen was administered by s.c. injection either in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Arm title
 Dulaglutide 1.5 mg
Arm description
 Subjects received s.c. injections of dulaglutide 1.5 mg OW for treatment duration of 40 weeks. Subjects were followed for 5 weeks after completion of treatment period.
Arm type
 Active comparator

Investigational medicinal product name
Dulaglutide
Investigational medicinal product code
Other name
Trulicity®
Pharmaceutical forms
Solution for injection
Routes of administration
Subcutaneous use
Dosage and administration details
Dulaglutide solution for injection in a pre-filled pen was administered by s.c. injection either in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same day of the week during the trial.

Number of subjects in period 1
Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Started
301
300
299
299
Completed
279
279
287
284
Not completed
22
21
12
15
     Adverse event, serious fatal
1
1
2
2
     Missing follow-up information
4
4
4
2
     Adverse event, non-fatal
-
-
1
-
     Consent withdrawn by subject
12
8
1
5
     Lost to follow-up
5
8
4
6

Baseline characteristics

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Baseline characteristics reporting groups
Reporting group title
Semaglutide 0.5 mg
Reporting group description
 Subjects received subcutaneous (s.c., under the skin) injections of semaglutide once weekly (OW) for treatment duration of 40 weeks. Subjects received semaglutide 0.25 mg for 4 weeks (weeks 1 to 4) followed by 0.5 mg for 36 weeks (weeks 5 to 40). Subjects were followed for 5 weeks after completion of treatment period.

Reporting group title
Semaglutide 1.0 mg
Reporting group description
 Subjects received s.c. injections of semaglutide OW for treatment duration of 40 weeks. Subjects received semaglutide 0.25 mg for 4 weeks (weeks 1 to 4) followed by 0.5 mg for another 4 weeks (weeks 5 to 8) and then semaglutide 1.0 mg for remaining 32 weeks (weeks 9-40). Subjects were followed for 5 weeks after completion of treatment period.

Reporting group title
Dulaglutide 0.75 mg
Reporting group description
 Subjects received s.c. injections of dulaglutide 0.75 mg OW for treatment duration of 40 weeks. Subjects were followed for 5 weeks after completion of treatment period.

Reporting group title
Dulaglutide 1.5 mg
Reporting group description
 Subjects received s.c. injections of dulaglutide 1.5 mg OW for treatment duration of 40 weeks. Subjects were followed for 5 weeks after completion of treatment period.

Reporting group values
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg Total
Number of subjects
 301 300 299 299 1199
Age Categorical
Units: Subjects
    Adults (18-64 years)
 222 247 238 232 939
    From 65-74 years
 67 45 53 60 225
    75-84 years
 12 8 8 7 35
Age Continuous
Units: years
    arithmetic mean (standard deviation)
 56 ± 10.9 55 ± 10.6 55 ± 10.4 56 ± 10.6 -
Gender Categorical
Units: Subjects
    Female
 169 162 160 171 662
    Male
 132 138 139 128 537
Race
Units: Subjects
    American Indian or Alaska Native
 0 0 0 0 0
    Asian
 50 38 48 55 191
    Native Hawaiian or Other Pacific Islander
 0 0 0 0 0
    Black or African American
 17 18 17 18 70
    White
 233 243 232 220 928
    More than one race
 0 0 0 0 0
    Unknown or Not Reported
 1 1 2 6 10
Ethnicity
Units: Subjects
    Hispanic or Latino
 29 35 31 43 138
    Not Hispanic or Latino
 272 265 268 256 1061
Glycosylated haemoglobin (Hb1Ac)
Units: percentage of HbA1c
    arithmetic mean (standard deviation)
 8.3 ± 0.96 8.2 ± 0.92 8.2 ± 0.91 8.2 ± 0.89 -
Body weight
Units: kg
    arithmetic mean (standard deviation)
 96.4 ± 24.38 95.5 ± 20.90 95.6 ± 23.01 93.4 ± 21.79 -
Fasting plasma glucose
Number of subject analysed=298, 299, 297, 297 for semaglutide 0.5 mg, semaglutide 1.0 mg, dulaglutide 0.75 mg and dulaglutide 1.5 mg, respectively.
Units: mmol/L
    arithmetic mean (standard deviation)
 9.8 ± 2.54 9.8 ± 2.58 9.7 ± 2.65 9.6 ± 2.29 -

End points

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End points reporting groups
Reporting group title
Semaglutide 0.5 mg
Reporting group description
 Subjects received subcutaneous (s.c., under the skin) injections of semaglutide once weekly (OW) for treatment duration of 40 weeks. Subjects received semaglutide 0.25 mg for 4 weeks (weeks 1 to 4) followed by 0.5 mg for 36 weeks (weeks 5 to 40). Subjects were followed for 5 weeks after completion of treatment period.

Reporting group title
Semaglutide 1.0 mg
Reporting group description
 Subjects received s.c. injections of semaglutide OW for treatment duration of 40 weeks. Subjects received semaglutide 0.25 mg for 4 weeks (weeks 1 to 4) followed by 0.5 mg for another 4 weeks (weeks 5 to 8) and then semaglutide 1.0 mg for remaining 32 weeks (weeks 9-40). Subjects were followed for 5 weeks after completion of treatment period.

Reporting group title
Dulaglutide 0.75 mg
Reporting group description
 Subjects received s.c. injections of dulaglutide 0.75 mg OW for treatment duration of 40 weeks. Subjects were followed for 5 weeks after completion of treatment period.

Reporting group title
Dulaglutide 1.5 mg
Reporting group description
 Subjects received s.c. injections of dulaglutide 1.5 mg OW for treatment duration of 40 weeks. Subjects were followed for 5 weeks after completion of treatment period.

Primary: Change in HbA1c

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End point title
 Change in HbA1c
End point description
Results are based on HbA1c data from on-treatment without rescue medication observation period. The ‘on-treatment’ observation period was the period where the subject was considered to be exposed to trial product. The ‘on-treatment without rescue medication’ observation period was a subset of the ‘on-treatment’ observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the ‘on-treatment’ observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Analysis was based on FAS (all randomised subjects exposed to at least one dose of trial product).
End point type
Primary
End point timeframe
From baseline to week 40
End point values
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Number of subjects analysed
301
300
299
299
Units: percentage of HbA1c
    least squares mean (standard error)
-1.51 ± 0.06
-1.78 ± 0.06
-1.11 ± 0.05
-1.37 ± 0.06
Statistical analysis title
 Semaglutide 0.5 mg vs. Dulaglutide 0.75 mg
Comparison groups
Dulaglutide 0.75 mg v Semaglutide 0.5 mg
Number of subjects included in analysis
600
Analysis specification
Pre-specified
Analysis type
 non-inferiority [1]
P-value
 < 0.0001
Method
 Mixed models analysis
Parameter type
 Treatment difference
Point estimate
-0.4
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -0.55
     upper limit
 -0.25
Variability estimate
Standard error of the mean
Dispersion value
0.08
Notes
[1] - Non-Inferiority margin: 0.4
Statistical analysis title
 Semaglutide 0.5 mg vs. Dulaglutide 0.75 mg
Comparison groups
Semaglutide 0.5 mg v Dulaglutide 0.75 mg
Number of subjects included in analysis
600
Analysis specification
Pre-specified
Analysis type
 superiority
P-value
 < 0.0001
Method
 Mixed models analysis
Parameter type
 Treatment difference
Point estimate
-0.4
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -0.55
     upper limit
 -0.25
Variability estimate
Standard error of the mean
Dispersion value
0.08
Statistical analysis title
 Semaglutide 1.0 mg vs. Dulaglutide 1.5 mg
Comparison groups
Semaglutide 1.0 mg v Dulaglutide 1.5 mg
Number of subjects included in analysis
599
Analysis specification
Pre-specified
Analysis type
 non-inferiority [2]
P-value
 < 0.0001
Method
 Mixed models analysis
Parameter type
 Treatment difference
Point estimate
-0.41
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -0.57
     upper limit
 -0.25
Variability estimate
Standard error of the mean
Dispersion value
0.08
Notes
[2] - Non-Inferiority margin: 0.04
Statistical analysis title
 Semaglutide 1.0 mg vs. Dulaglutide 1.5 mg
Comparison groups
Semaglutide 1.0 mg v Dulaglutide 1.5 mg
Number of subjects included in analysis
599
Analysis specification
Pre-specified
Analysis type
 superiority
P-value
 < 0.0001
Method
 Mixed models analysis
Parameter type
 Treatment difference
Point estimate
-0.41
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -0.57
     upper limit
 -0.25
Variability estimate
Standard error of the mean
Dispersion value
0.08

Secondary: Change in body weight (kg)

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End point title
 Change in body weight (kg)
End point description
Results are based on body weight data from on-treatment without rescue medication observation period. The ‘on-treatment’ observation period was the period where the subject was considered to be exposed to trial product. The ‘on-treatment without rescue medication’ observation period was a subset of the ‘on -treatment’ observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the ‘on-treatment’ observation period or initiation of rescue medication. Analysis was based on FAS. Number of subjects analysed=number of subjects with available data for body weight.
End point type
Secondary
End point timeframe
From baseline to week 40
End point values
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Number of subjects analysed
301
300
299
298
Units: kg
    least squares mean (standard error)
-4.56 ± 0.28
-6.53 ± 0.28
-2.30 ± 0.27
-2.98 ± 0.27
Statistical analysis title
 Semaglutide 1.0 mg vs. Dulaglutide 1.5 mg
Comparison groups
Semaglutide 1.0 mg v Dulaglutide 1.5 mg
Number of subjects included in analysis
598
Analysis specification
Pre-specified
Analysis type
 superiority
P-value
 < 0.0001
Method
 Mixed models analysis
Parameter type
 Treatment difference
Point estimate
-3.55
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -4.32
     upper limit
 -2.78
Variability estimate
Standard error of the mean
Dispersion value
0.39
Statistical analysis title
 Semaglutide 0.5 mg vs. Dulaglutide 0.75 mg
Comparison groups
Semaglutide 0.5 mg v Dulaglutide 0.75 mg
Number of subjects included in analysis
600
Analysis specification
Pre-specified
Analysis type
 superiority
P-value
 < 0.0001
Method
 Mixed models analysis
Parameter type
 Treatment difference
Point estimate
-2.26
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -3.02
     upper limit
 -1.51
Variability estimate
Standard error of the mean
Dispersion value
0.39

Secondary: Change in fasting plasma glucose

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End point title
 Change in fasting plasma glucose
End point description
Results are based on fasting plasma glucose data from on-treatment without rescue medication observation period. The ‘on-treatment’ observation period was the period where the subject was considered to be exposed to trial product. The ‘on-treatment without rescue medication’ observation period was a subset of the ‘on -treatment’ observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the ‘on-treatment’ observation period or initiation of rescue medication. Analysis was based on FAS. Number of participants analysed=number of participants with available data for fasting plasma glucose.
End point type
Secondary
End point timeframe
From baseline to week 40
End point values
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Number of subjects analysed
298
299
297
297
Units: mmol/L
    least squares mean (standard error)
-2.18 ± 0.12
-2.83 ± 0.12
-1.87 ± 0.12
-2.25 ± 0.12
No statistical analyses for this end point

Secondary: Change in systolic and diastolic blood pressure

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End point title
 Change in systolic and diastolic blood pressure
End point description
Results are based on systolic and diastolic blood pressure data from on-treatment without rescue medication observation period. The ‘on-treatment’ observation period was the period where the subject was considered to be exposed to trial product. The ‘on-treatment without rescue medication’ observation period was a subset of the ‘on -treatment’ observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the ‘on-treatment’ observation period or initiation of rescue medication. Analysis was based on FAS.
End point type
Secondary
End point timeframe
From baseline to week 40
End point values
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Number of subjects analysed
301
300
299
299
Units: mmHg
least squares mean (standard error)
    Diastolic BP
-0.57 ± 0.48
-2.05 ± 0.49
-0.35 ± 0.47
-0.03 ± 0.47
    Systolic BP
-2.44 ± 0.76
-4.88 ± 0.77
-2.16 ± 0.75
-2.86 ± 0.75
No statistical analyses for this end point

Secondary: Overall scores for patient reported outcomes: Diabetes Treatment Satisfaction Questionnaire

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End point title
 Overall scores for patient reported outcomes: Diabetes Treatment Satisfaction Questionnaire
End point description
The questionnaire contains 8 items and evaluates subjects’ diabetes treatment in terms of convenience, flexibility and general feelings towards treatment. The result presented is 'Treatment Satisfaction' summary score (sum of 6 of the 8 items). Response options: 6 (best case) to 0 (worst case). Total scores range: 0-36. Higher scores=higher satisfaction. Results are based on data from on-treatment without rescue medication observation period. The ‘on-treatment’ observation period was period where subject was considered to be exposed to trial product. The ‘on-treatment without rescue medication’ observation period was a subset of the ‘on -treatment’ observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This includes observations recorded at, or after the date of first dose of trial product and not after first occurrence of following: end-date of the ‘on-treatment’ observation period or initiation of rescue medication
End point type
Secondary
End point timeframe
From baseline to week 40
End point values
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Number of subjects analysed
301 [3]
299 [4]
299 [5]
298 [6]
Units: units on a scale
    least squares mean (standard error)
4.60 ± 0.28
4.55 ± 0.29
4.52 ± 0.28
4.65 ± 0.28
Notes
[3] - Number of participants with available data for diabetes treatment satisfaction questionnaire.
[4] - Number of participants with available data for diabetes treatment satisfaction questionnaire
[5] - Number of participants with available data for diabetes treatment satisfaction questionnaire
[6] - Number of participants with available data for diabetes treatment satisfaction questionnaire
No statistical analyses for this end point

Secondary: Subjects who achieve (yes/no) HbA1c ≤6.5% (48 mmol/mol) American Association of Clinical Endocrinologists target

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End point title
 Subjects who achieve (yes/no) HbA1c ≤6.5% (48 mmol/mol) American Association of Clinical Endocrinologists target
End point description
Percentage of subjects who achieved HbA1c target below or equal to 6.5% (48 mmol/mol) after 40 weeks of treatment. Results are based on data from on-treatment without rescue medication period. The ‘on-treatment’ observation period was the period where the subject was considered to be exposed to trial product. The ‘on-treatment without rescue medication’ observation period was a subset of the ‘on -treatment’ observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the ‘on-treatment’ observation period or initiation of rescue medication. Missing data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Results are based on the FAS.
End point type
Secondary
End point timeframe
After 40 weeks treatment
End point values
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Number of subjects analysed
301
300
299
299
Units: percentage of subjects
number (not applicable)
    Yes
49.2
66.7
34.1
47.2
    No
50.8
33.3
65.9
52.8
No statistical analyses for this end point

Adverse events

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Adverse events information
Timeframe for reporting adverse events
Baseline (week 0) to week 40 + follow up of 5 weeks (including a visit window of +7 days)
Adverse event reporting additional description
A TEAE was defined as an AE with onset in the ‘on-treatment’ period (information collected while subjects were considered as exposed to trial product). This corresponded to information collected from first administration of trial product until the follow-up (5 weeks after the last treatment including a visit window of +7 days)
Assessment type
 Systematic
Dictionary used for adverse event reporting
Dictionary name
 MedDRA
Dictionary version
19
Reporting groups
Reporting group title
Semaglutide 0.5 mg
Reporting group description
 Subjects received s.c. injections of semaglutide OW for treatment duration of 40 weeks. Subjects received semaglutide 0.25 mg for 4 weeks (weeks 1 to 4) followed by 0.5 mg for 36 weeks (weeks 5 to 40).

Reporting group title
Semaglutide 1.0 mg
Reporting group description
 Subjects received s.c. injections of semaglutide OW for treatment duration of 40 weeks. Subjects received semaglutide 0.25 mg for 4 weeks (weeks 1 to 4) followed by 0.5 mg for another 4 weeks (weeks 5 to 8) and then semaglutide 1.0 mg for remaining 32 weeks (weeks 9-40). Subjects were followed for 5 weeks after completion of treatment period.

Reporting group title
Dulaglutide 0.75 mg
Reporting group description
 Subjects received s.c. injections of dulaglutide 0.75 mg OW for treatment duration of 40 weeks. Subjects were followed for 5 weeks after completion of treatment period.

Reporting group title
Dulaglutide 1.5 mg
Reporting group description
 Subjects received s.c. injections of dulaglutide 1.5 mg OW for treatment duration of 40 weeks. Subjects were followed for 5 weeks after completion of treatment period.

Serious adverse events
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Total subjects affected by serious adverse events
     subjects affected / exposed
17 / 301 (5.65%)
23 / 300 (7.67%)
24 / 299 (8.03%)
22 / 299 (7.36%)
     number of deaths (all causes)
0
1
2
2
     number of deaths resulting from adverse events
0
0
0
0
Vascular disorders
Hypertensive crisis
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Surgical and medical procedures
Cardioversion
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Gastrectomy
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Hip arthroplasty
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Hospitalisation
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Hysterectomy
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Orchidectomy
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Lipoma
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 2
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Malignant neoplasm of ampulla of Vater
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Metastatic squamous cell carcinoma
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Pancreatic carcinoma stage IV
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
Rectal adenocarcinoma
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Rectal cancer
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Immune system disorders
Hypersensitivity
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
1 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Sarcoidosis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
General disorders and administration site conditions
Drowning
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
Multiple organ dysfunction syndrome
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
Non-cardiac chest pain
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Psychiatric disorders
Anxiety
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Depression
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Suicide attempt
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Reproductive system and breast disorders
Cystocele
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Uterine prolapse
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Injury, poisoning and procedural complications
Contusion
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Face injury
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
1 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Fall
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Femur fracture
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Meniscus injury
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Post procedural myocardial infarction
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Road traffic accident
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
1 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Tibia fracture
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Investigations
Lipase increased
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
1 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Cardiac disorders
Angina pectoris
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Angina unstable
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
2 / 299 (0.67%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 2
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Aortic valve stenosis
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Atrial fibrillation
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
2 / 299 (0.67%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 2
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Atrial flutter
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Atrioventricular block complete
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Cardio-respiratory arrest
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 1
Congestive cardiomyopathy
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Coronary artery stenosis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Myocardial infarction
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Ventricular extrasystoles
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Chronic obstructive pulmonary disease
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Epistaxis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Pulmonary embolism
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Nervous system disorders
Carpal tunnel syndrome
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
2 / 299 (0.67%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 2
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Cerebral infarction
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Diabetic neuropathy
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Hypoglycaemic unconsciousness
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
1 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Paraesthesia
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Ear and labyrinth disorders
Acute vestibular syndrome
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Gastrointestinal disorders
Abdominal pain
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
1 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Colitis
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Crohn's disease
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
1 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Gastroduodenitis
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Haemorrhoids
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Impaired gastric emptying
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
1 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Inguinal hernia
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Nausea
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Pancreatitis acute
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
1 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Pancreatolithiasis
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Rectal prolapse
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Vomiting
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Renal and urinary disorders
Nephrolithiasis
     subjects affected / exposed
1 / 301 (0.33%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Renal colic
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Ureterolithiasis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Hepatobiliary disorders
Cholecystitis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Cholecystitis acute
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
2 / 299 (0.67%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 2
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Cholelithiasis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Gallbladder pain
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Hepatic cirrhosis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Musculoskeletal and connective tissue disorders
Back pain
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
2 / 299 (0.67%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 2
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Intervertebral disc degeneration
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Intervertebral disc protrusion
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Musculoskeletal chest pain
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Spinal column stenosis
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Metabolism and nutrition disorders
Dehydration
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Diabetic complication
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
Hypercalcaemia
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
1 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Hypoglycaemia
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
1 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Infections and infestations
Appendicitis
     subjects affected / exposed
2 / 301 (0.66%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 2
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Bronchitis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Cellulitis
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Gastroenteritis viral
     subjects affected / exposed
0 / 301 (0.00%)
1 / 300 (0.33%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
HIV infection
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Kidney infection
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Perirectal abscess
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Pneumonia
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
Postoperative wound infection
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Pyelonephritis
     subjects affected / exposed
0 / 301 (0.00%)
0 / 300 (0.00%)
1 / 299 (0.33%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 0
0 / 0
0 / 1
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Sepsis
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
1 / 299 (0.33%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 1
Upper respiratory tract infection
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Urinary tract infection
     subjects affected / exposed
1 / 301 (0.33%)
0 / 300 (0.00%)
0 / 299 (0.00%)
0 / 299 (0.00%)
     occurrences causally related to treatment / all
0 / 1
0 / 0
0 / 0
0 / 0
     deaths causally related to treatment / all
0 / 0
0 / 0
0 / 0
0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events
 Semaglutide 0.5 mg Semaglutide 1.0 mg Dulaglutide 0.75 mg Dulaglutide 1.5 mg
Total subjects affected by non serious adverse events
     subjects affected / exposed
132 / 301 (43.85%)
134 / 300 (44.67%)
106 / 299 (35.45%)
139 / 299 (46.49%)
Investigations
Lipase increased
     subjects affected / exposed
19 / 301 (6.31%)
17 / 300 (5.67%)
16 / 299 (5.35%)
17 / 299 (5.69%)
     occurrences all number
23
17
17
20
Nervous system disorders
Headache
     subjects affected / exposed
25 / 301 (8.31%)
22 / 300 (7.33%)
12 / 299 (4.01%)
19 / 299 (6.35%)
     occurrences all number
35
30
20
30
Gastrointestinal disorders
Constipation
     subjects affected / exposed
16 / 301 (5.32%)
14 / 300 (4.67%)
10 / 299 (3.34%)
15 / 299 (5.02%)
     occurrences all number
18
14
10
18
Diarrhoea
     subjects affected / exposed
43 / 301 (14.29%)
41 / 300 (13.67%)
23 / 299 (7.69%)
53 / 299 (17.73%)
     occurrences all number
79
96
42
75
Nausea
     subjects affected / exposed
67 / 301 (22.26%)
63 / 300 (21.00%)
39 / 299 (13.04%)
60 / 299 (20.07%)
     occurrences all number
144
192
66
108
Vomiting
     subjects affected / exposed
30 / 301 (9.97%)
31 / 300 (10.33%)
12 / 299 (4.01%)
29 / 299 (9.70%)
     occurrences all number
50
48
16
40
Metabolism and nutrition disorders
Decreased appetite
     subjects affected / exposed
25 / 301 (8.31%)
27 / 300 (9.00%)
9 / 299 (3.01%)
31 / 299 (10.37%)
     occurrences all number
26
27
12
36
Infections and infestations
Nasopharyngitis
     subjects affected / exposed
15 / 301 (4.98%)
14 / 300 (4.67%)
17 / 299 (5.69%)
20 / 299 (6.69%)
     occurrences all number
16
16
20
24
Upper respiratory tract infection
     subjects affected / exposed
13 / 301 (4.32%)
10 / 300 (3.33%)
21 / 299 (7.02%)
16 / 299 (5.35%)
     occurrences all number
18
11
26
21

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Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date
Amendment
28 Oct 2016
The protocol was updated to include diabetic retinopathy complications in the risk-benefit assessment of semaglutide based on clinical findings from the phase 3a programme. Other minor language corrections and updates were also included for general clarification.

Interruptions (globally)
Were there any global interruptions to the trial? No

Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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