Download PDF

Clinical Trial Results:
A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients with Type 2 Diabetes (SURPASS-2)

Summary
EudraCT number	2018-004422-29
Trial protocol	GB
Global end of trial date	15 Feb 2021

Results information
Results version number	v1(current)
This version publication date	06 Feb 2022
First version publication date	06 Feb 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

I8F-MC-GPGL

ISRCTN number

US NCT number

NCT03987919

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 17001

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Feb 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Feb 2021

Was the trial ended prematurely?

Main objective of the trial

The reason for this study is to compare the effect of the study drug tirzepatide to semaglutide on blood sugar levels in participants with type 2 diabetes. The study will last approximately 47 weeks and may include about 12 visits.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Jul 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 640

Country: Number of subjects enrolled

Australia: 46

Country: Number of subjects enrolled

Brazil: 147

Country: Number of subjects enrolled

Canada: 59

Country: Number of subjects enrolled

Israel: 87

Country: Number of subjects enrolled

Mexico: 352

Country: Number of subjects enrolled

Puerto Rico: 19

Country: Number of subjects enrolled

United Kingdom: 72

Country: Number of subjects enrolled

United States: 456

Worldwide total number of subjects

1878

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1420

From 65 to 84 years

456

85 years and over

Subject disposition

Top of page

Recruitment details

1879 participants were randomized in to the study and only 1878 participants received at least one dose of study drug.

Screening details

No Text Available

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

5 mg Tirzepatide

Arm description

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

Arm type

Experimental

Investigational medicinal product name

Tirzepatide

Investigational medicinal product code

Other name

LY3298176

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

5 mg tirzepatide administered SC once a week.

10 mg Tirzepatide

Arm description

10 mg tirzepatide administered SC once a week.

Arm type

Experimental

Investigational medicinal product name

Tirzepatide

Investigational medicinal product code

Other name

LY3298176

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mg tirzepatide administered SC once a week.

15 mg Tirzepatide

Arm description

15 mg tirzepatide administered SC once a week.

Arm type

Experimental

Investigational medicinal product name

Tirzepatide

Investigational medicinal product code

Other name

LY3298176

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

15 mg tirzepatide administered SC once a week.

1 mg Semaglutide

Arm description

1 mg semaglutide administered SC once a week.

Arm type

Active comparator

Investigational medicinal product name

Semaglutide

Investigational medicinal product code

Other name

Ozempic

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1 mg semaglutide administered SC once a week.

Number of subjects in period 1	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Started	470	469	470	469
Received at least one dose of study drug	470	469	470	469
Completed	451	442	446	443
Not completed	19	27	24	26
Adverse event, serious fatal	4	4	4	1
Consent withdrawn by subject	7	7	8	4
Physician decision	-	2	-	4
Study terminated by Sponsor	-	-	-	1
Adverse event, non-fatal	1	4	1	3
Other – as reported by the investigator	1	3	2	-
Pregnancy	1	-	1	1
Lost to follow-up	5	6	8	12
Protocol deviation	-	1	-	-

Baseline characteristics

Top of page

Reporting group title

5 mg Tirzepatide

Reporting group description

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

Reporting group title

10 mg Tirzepatide

Reporting group description

10 mg tirzepatide administered SC once a week.

Reporting group title

15 mg Tirzepatide

Reporting group description

15 mg tirzepatide administered SC once a week.

Reporting group title

1 mg Semaglutide

Reporting group description

1 mg semaglutide administered SC once a week.

Reporting group values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide	Total
Number of subjects	470	469	470	469	1878
Age categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					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)					0
From 65-84 years					0
85 years and over					0
Age continuous
Units: years
arithmetic mean (standard deviation)	56.3 ± 10.0	57.2 ± 10.5	55.9 ± 10.4	56.9 ± 10.8	-
Gender categorical
Units: Subjects
Female	265	231	256	244	996
Male	205	238	214	225	882
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	325	322	334	336	1317
Not Hispanic or Latino	145	147	136	133	561
Unknown or Not Reported	0	0	0	0	0
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	53	53	57	45	208
Asian	6	11	5	3	25
Native Hawaiian or Other Pacific Islander	0	0	1	2	3
Black or African American	28	21	15	15	79
White	382	376	392	401	1551
More than one race	1	8	0	3	12
Unknown or Not Reported	0	0	0	0	0
Region of Enrollment
Units: Subjects
Argentina	158	160	161	161	640
Australia	12	11	12	11	46
Brazil	37	37	36	37	147
Canada	15	15	14	15	59
Israel	22	22	22	21	87
Mexico	89	87	88	88	352
Puerto Rico	6	4	6	3	19
United Kingdom	18	18	18	18	72
United States	113	115	113	115	456
Hemoglobin A1c
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.
Units: Percentage of HbA1c
arithmetic mean (standard deviation)	8.32 ± 1.08	8.30 ± 1.02	8.26 ± 1.00	8.25 ± 1.01	-

End points

Top of page

Reporting group title

5 mg Tirzepatide

Reporting group description

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

Reporting group title

10 mg Tirzepatide

Reporting group description

10 mg tirzepatide administered SC once a week.

Reporting group title

15 mg Tirzepatide

Reporting group description

15 mg tirzepatide administered SC once a week.

Reporting group title

1 mg Semaglutide

Reporting group description

1 mg semaglutide administered SC once a week.

Primary: Change from Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

Top of page

End point title

Change from Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) ^[1]

End point description

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). Analysis Population Description (APD): All participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline HbA1c value, excluding patients who discontinued study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

End point type

Primary

End point timeframe

Baseline, Week 40

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per SAP, this outcome is planned to compare 10 mg Tirzepatide and 15 mg Tirzepatide with 1 mg Semaglutide.

End point values	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	459	464	461
Units: Percentage of HbA1c
least squares mean (standard error)	-2.37 ± 0.048	-2.46 ± 0.048	-1.86 ± 0.048

Change from Baseline in Hemoglobin A1c (HbA1c)

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

920

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

-0.38

Change from Baseline in Hemoglobin A1c (HbA1c)

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

925

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

-0.47

Secondary: Change from Baseline in HbA1c (5 mg)

Top of page

End point title

Change from Baseline in HbA1c (5 mg) ^[2]

End point description

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline HbA1c value, excluding patients who discontinued study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

End point type

Secondary

End point timeframe

Baseline, Week 40

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per SAP, this outcome is planned to compare 5 mg Tirzepatide with 1 mg Semaglutide.

End point values	5 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	461	461
Units: Percentage of HbA1c
least squares mean (standard error)	-2.09 ± 0.047	-1.86 ± 0.048

Change from Baseline in HbA1c (5 mg)

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

922

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

-0.1

Secondary: Change from Baseline in Body Weight

Top of page

End point title

Change from Baseline in Body Weight

End point description

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline body weight value, excluding patients who discontinued study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

End point type

Secondary

End point timeframe

Baseline, Week 40

End point values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	461	459	464	462
Units: Kilograms (kg)
least squares mean (standard error)	-7.8 ± 0.33	-10.3 ± 0.34	-12.4 ± 0.34	-6.2 ± 0.33

Change from Baseline in Body Weight

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

923

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

-0.7

Change from Baseline in Body Weight

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

921

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

-3.2

Change from Baseline in Body Weight

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

926

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-6.2

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

-5.3

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <7%

Top of page

End point title

Percentage of Participants Achieving an HbA1c Target Value of <7%

End point description

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. APD: All participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline HbA1c value, excluding patients who discontinued study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

End point type

Secondary

End point timeframe

Week 40

End point values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	461	459	464	461
Units: Percentage of Participants
number (not applicable)	85.47	88.89	92.24	81.13

Percentage of Participants Achieving an HbA1c <7%

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

922

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.023

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.54

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

2.23

Percentage of Participants Achieving an HbA1c <7%

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

920

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.14

Confidence interval

level

95%

sides

2-sided

lower limit

1.44

upper limit

3.17

Percentage of Participants Achieving an HbA1c <7%

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

925

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.03

Confidence interval

level

95%

sides

2-sided

lower limit

1.97

upper limit

4.66

Secondary: Change from Baseline in Fasting Serum Glucose

Top of page

End point title

Change from Baseline in Fasting Serum Glucose

End point description

Change from Baseline in Fasting Serum Glucose. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline FSG value, excluding patients who discontinued study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

End point type

Secondary

End point timeframe

Baseline, Week 40

End point values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	461	458	464	459
Units: milligram per Deciliter (mg/dL)
least squares mean (standard error)	-56.0 ± 1.57	-61.6 ± 1.60	-63.4 ± 1.59	-48.6 ± 1.58

Change from Baseline in Fasting Serum Glucose

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

920

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-7.3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

-3

Change from Baseline in Fasting Serum Glucose

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

917

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-13

Confidence interval

level

95%

sides

2-sided

lower limit

-17.4

upper limit

-8.6

Change from Baseline in Fasting Serum Glucose

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

923

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-14.7

Confidence interval

level

95%

sides

2-sided

lower limit

-19.1

upper limit

-10.3

Secondary: Mean Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

Top of page

End point title

Mean Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

End point description

The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline SMBG value, excluding patients who discontinued study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

End point type

Secondary

End point timeframe

Baseline, Week 40

End point values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	424	412	413	414
Units: mg/dL
least squares mean (standard error)	-65.4 ± 1.04	-70.6 ± 1.05	-74.3 ± 1.05	-61.4 ± 1.04

No statistical analyses for this end point

Secondary: Percentage of Participants who Achieved Weight Loss ≥5%

Top of page

End point title

Percentage of Participants who Achieved Weight Loss ≥5%

End point description

Percentage of Participants who Achieved Weight Loss ≥5%. APD: All participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline weight loss, excluding patients who discontinued study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

End point type

Secondary

End point timeframe

Week 40

End point values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	461	459	464	462
Units: Percentage of Participants
number (not applicable)	68.55	82.35	86.21	58.44

Weight Loss ≥5%

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

923

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.58

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

2.08

Weight Loss ≥5%

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

921

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.49

Confidence interval

level

95%

sides

2-sided

lower limit

2.57

upper limit

4.75

Weight Loss ≥5%

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

926

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

3.32

upper limit

6.38

Secondary: Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

Top of page

End point title

Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

End point description

DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 40 or early termination. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS Mean was determined by ANCOVA with Baseline DTSQs + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment (Type III sum of squares).

End point type

Secondary

End point timeframe

Baseline, Week 40

End point values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	419 ^[3]	399 ^[4]	398	412 ^[5]
Units: Units on a Scale
least squares mean (standard error)
Hyperglycemia	-1.3 ± 0.10	-1.4 ± 0.10	-1.5 ± 0.10	-1.1 ± 0.10
Hypoglycemia	-0.7 ± 0.10	-0.7 ± 0.10	-0.8 ± 0.10	-0.7 ± 0.10
Total Score	15.7 ± 0.18	15.6 ± 0.19	16.1 ± 0.19	15.8 ± 0.19

Notes
[3] - Hyperglycemia: 418 Hypoglycemia: 416 Total Score: 419
[4] - Hyperglycemia: 399 Hypoglycemia: 398 Total Score: 399
[5] - Hyperglycemia: 411 Hypoglycemia: 412 Total Score: 411

DTSQc

Statistical analysis description

Hyperglycemia

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

831

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.084

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.03

Notes
[6] - Hyperglycemia

DTSQc

Statistical analysis description

Hyperglycemia

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

811

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 0.05

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

Notes
[7] - Hyperglycemia

DTSQc

Statistical analysis description

Hyperglycemia

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

810

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

= 0.005

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.66

upper limit

-0.12

Notes
[8] - Hyperglycemia

DTSQc

Statistical analysis description

Hypoglycemia

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

831

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.688

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

0.22

Notes
[9] - Hypoglycemia

DTSQc

Statistical analysis description

Hypoglycemia

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

811

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.909

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.26

Notes
[10] - Hypoglycemia

DTSQc

Statistical analysis description

Hypoglycemia

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

810

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

= 0.358

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.15

Notes
[11] - Hypoglycemia

DTSQc

Statistical analysis description

Total Score

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

831

Analysis specification

Pre-specified

Analysis type

superiority ^[12]

P-value

= 0.701

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.62

upper limit

0.41

Notes
[12] - Total Score

DTSQc

Statistical analysis description

Total Score

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

811

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

= 0.341

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

0.27

Notes
[13] - Total Score

DTSQc

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

810

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

= 0.321

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.79

Notes
[14] - Total Score

Secondary: Rate of Hypoglycemia with Blood Glucose <54 milligram/deciliter (mg/dL) [<3.0 millimole/liter (mmol/L)] or Severe Hypoglycemia

Top of page

End point title

Rate of Hypoglycemia with Blood Glucose <54 milligram/deciliter (mg/dL) [<3.0 millimole/liter (mmol/L)] or Severe Hypoglycemia

End point description

The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL) (<3.0 mmol/L] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment. APD: All randomized participants who received at least one dose of study drug.

End point type

Secondary

End point timeframe

Baseline through Safety Follow-Up (Up to Week 44)

End point values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	470	469	470	469
Units: Episodes/participant/365.25 days
arithmetic mean (standard error)	0.0102 ± 0.00423	0.0046 ± 0.00488	0.0202 ± 0.00840	0.0046 ± 0.00340

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <5.7%

Top of page

End point title

Percentage of Participants Achieving an HbA1c Target Value of <5.7%

End point description

Percentage of Participants Achieving an HbA1c Target Value of <5.7%. APD: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline HbA1c value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug

End point type

Secondary

End point timeframe

Week 40

End point values	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Number of subjects analysed	461	459	464	461
Units: Percentage of Participants
number (not applicable)	29.28	44.66	50.86	19.74

HbA1c Target Value of <5.7%

Comparison groups

10 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

920

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.94

Confidence interval

level

95%

sides

2-sided

lower limit

2.88

upper limit

5.39

HbA1c Target Value of <5.7%

Comparison groups

15 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

925

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.1

Confidence interval

level

95%

sides

2-sided

lower limit

3.73

upper limit

6.97

HbA1c Target Value of <5.7%

Comparison groups

5 mg Tirzepatide v 1 mg Semaglutide

Number of subjects included in analysis

922

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.86

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

2.57

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline, Safety follow-up (44 Weeks)

Adverse event reporting additional description

All randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

5 mg Tirzepatide

Reporting group description

5 mg tirzepatide administered subcutaneously (SC) once a week.

Reporting group title

15 mg Tirzepatide

Reporting group description

15 mg tirzepatide administered SC once a week.

Reporting group title

1 mg Semaglutide

Reporting group description

1 mg of semaglutide administered SC once a week.

Reporting group title

10 mg Tirzepatide

Reporting group description

10 mg tirzepatide administered SC once a week.

Serious adverse events	5 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide	10 mg Tirzepatide
Total subjects affected by serious adverse events
subjects affected / exposed	33 / 470 (7.02%)	27 / 470 (5.74%)	13 / 469 (2.77%)	25 / 469 (5.33%)
number of deaths (all causes)	4	4	1	4
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
adenocarcinoma
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
endometrial adenocarcinoma
alternative dictionary used: MedDRA 23.1
subjects affected / exposed ^[1]	1 / 265 (0.38%)	0 / 256 (0.00%)	0 / 244 (0.00%)	0 / 231 (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
glioblastoma multiforme
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
lung carcinoma cell type unspecified stage iii
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
metastatic squamous cell carcinoma
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
non-hodgkin's lymphoma
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
renal cell carcinoma
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
squamous cell carcinoma of skin
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
uterine leiomyoma
alternative dictionary used: MedDRA 23.1
subjects affected / exposed ^[2]	0 / 265 (0.00%)	1 / 256 (0.39%)	0 / 244 (0.00%)	0 / 231 (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
uterine neoplasm
alternative dictionary used: MedDRA 23.1
subjects affected / exposed ^[3]	1 / 265 (0.38%)	0 / 256 (0.00%)	0 / 244 (0.00%)	0 / 231 (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
Vascular disorders
deep vein thrombosis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
hypertension
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
orthostatic hypotension
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
peripheral vascular disorder
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
venous thrombosis limb
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
Surgical and medical procedures
abdominal hernia repair
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
General disorders and administration site conditions
chest pain
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
death
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
pyrexia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
sudden death
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
Reproductive system and breast disorders
metrorrhagia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed ^[4]	1 / 265 (0.38%)	0 / 256 (0.00%)	0 / 244 (0.00%)	0 / 231 (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
uterine prolapse
alternative dictionary used: MedDRA 23.1
subjects affected / exposed ^[5]	0 / 265 (0.00%)	0 / 256 (0.00%)	1 / 244 (0.41%)	0 / 231 (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
asthma
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
chronic obstructive pulmonary disease
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
dyspnoea
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
pleural effusion
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
pulmonary embolism
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
respiratory failure
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
post-traumatic stress disorder
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
suicide attempt
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
Investigations
amylase increased
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
coronavirus test positive
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
lipase increased
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
Injury, poisoning and procedural complications
ankle fracture
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
femur fracture
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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 fracture
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
intentional overdose
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
ligament injury
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
multiple injuries
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
traumatic amputation
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
upper limb fracture
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
wrist fracture
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
Cardiac disorders
acute myocardial infarction
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	2 / 470 (0.43%)	2 / 470 (0.43%)	0 / 469 (0.00%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	0 / 3	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
angina unstable
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
atrial fibrillation
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	2 / 470 (0.43%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
atrial flutter
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
cardiac failure
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
cardio-respiratory arrest
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
coronary artery disease
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
ventricular tachycardia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
Nervous system disorders
cerebellar infarction
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
cerebrovascular accident
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	2 / 470 (0.43%)	0 / 469 (0.00%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
headache
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
ischaemic stroke
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
syncope
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
Eye disorders
retinal vein occlusion
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
abdominal pain upper
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
constipation
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
epiploic appendagitis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
gastrointestinal haemorrhage
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
inguinal hernia, obstructive
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
irritable bowel syndrome
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
lower gastrointestinal haemorrhage
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
nausea
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
strangulated umbilical hernia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
Hepatobiliary disorders
cholecystitis acute
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	2 / 470 (0.43%)	0 / 469 (0.00%)	2 / 469 (0.43%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
diabetic ulcer
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
acute kidney injury
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
end stage renal disease
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
nephrolithiasis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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 / 0
urinary tract obstruction
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
Endocrine disorders
acromegaly
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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 and connective tissue disorders
back pain
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	0 / 469 (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
osteoarthritis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
Infections and infestations
appendicitis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
bacteraemia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	1 / 469 (0.21%)
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
covid-19
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	1 / 469 (0.21%)	1 / 469 (0.21%)
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
covid-19 pneumonia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	2 / 470 (0.43%)	2 / 470 (0.43%)	4 / 469 (0.85%)	2 / 469 (0.43%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
cellulitis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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 infective
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
complicated appendicitis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
dengue fever
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
epididymitis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed ^[6]	1 / 205 (0.49%)	0 / 214 (0.00%)	0 / 225 (0.00%)	0 / 238 (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
escherichia bacteraemia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
lower respiratory tract infection
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
osteomyelitis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (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
pharyngeal abscess
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	1 / 469 (0.21%)
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
pneumonia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	1 / 470 (0.21%)	1 / 469 (0.21%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
pyelonephritis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	0 / 470 (0.00%)	0 / 469 (0.00%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
sepsis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
suspected covid-19
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
urinary tract infection
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	0 / 470 (0.00%)	0 / 469 (0.00%)	2 / 469 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
urosepsis
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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
hypoglycaemia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	1 / 470 (0.21%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
hyponatraemia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	0 / 470 (0.00%)	1 / 470 (0.21%)	0 / 469 (0.00%)	0 / 469 (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

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	5 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide	10 mg Tirzepatide
Total subjects affected by non serious adverse events
subjects affected / exposed	170 / 470 (36.17%)	202 / 470 (42.98%)	172 / 469 (36.67%)	187 / 469 (39.87%)
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	14 / 470 (2.98%)	24 / 470 (5.11%)	24 / 469 (5.12%)	20 / 469 (4.26%)
occurrences all number	16	30	29	25
constipation
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	31 / 470 (6.60%)	21 / 470 (4.47%)	27 / 469 (5.76%)	21 / 469 (4.48%)
occurrences all number	35	23	32	23
diarrhoea
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	62 / 470 (13.19%)	65 / 470 (13.83%)	54 / 469 (11.51%)	77 / 469 (16.42%)
occurrences all number	120	102	68	98
dyspepsia
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	34 / 470 (7.23%)	43 / 470 (9.15%)	31 / 469 (6.61%)	29 / 469 (6.18%)
occurrences all number	46	51	42	43
nausea
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	82 / 470 (17.45%)	104 / 470 (22.13%)	84 / 469 (17.91%)	90 / 469 (19.19%)
occurrences all number	110	136	126	121
vomiting
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	27 / 470 (5.74%)	46 / 470 (9.79%)	39 / 469 (8.32%)	39 / 469 (8.32%)
occurrences all number	35	61	53	54
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 23.1
subjects affected / exposed	35 / 470 (7.45%)	42 / 470 (8.94%)	25 / 469 (5.33%)	34 / 469 (7.25%)
occurrences all number	38	51	26	43

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

26 Jun 2020

Protocol (b): Added language about the mobile (inhome) healthcare visits.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients with Type 2 Diabetes (SURPASS-2)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

Primary: Change from Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

Secondary: Change from Baseline in HbA1c (5 mg)

Secondary: Change from Baseline in HbA1c (5 mg)

Secondary: Change from Baseline in Body Weight

Secondary: Change from Baseline in Body Weight

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <7%

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <7%

Secondary: Change from Baseline in Fasting Serum Glucose

Secondary: Change from Baseline in Fasting Serum Glucose

Secondary: Mean Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

Secondary: Mean Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

Secondary: Percentage of Participants who Achieved Weight Loss ≥5%

Secondary: Percentage of Participants who Achieved Weight Loss ≥5%

Secondary: Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

Secondary: Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

Secondary: Rate of Hypoglycemia with Blood Glucose <54 milligram/deciliter (mg/dL) [<3.0 millimole/liter (mmol/L)] or Severe Hypoglycemia

Secondary: Rate of Hypoglycemia with Blood Glucose <54 milligram/deciliter (mg/dL) [<3.0 millimole/liter (mmol/L)] or Severe Hypoglycemia

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <5.7%

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <5.7%

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients with Type 2 Diabetes (SURPASS-2)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

Primary: Change from Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

Secondary: Change from Baseline in HbA1c (5 mg)

Secondary: Change from Baseline in HbA1c (5 mg)

Secondary: Change from Baseline in Body Weight

Secondary: Change from Baseline in Body Weight

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <7%

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <7%

Secondary: Change from Baseline in Fasting Serum Glucose

Secondary: Change from Baseline in Fasting Serum Glucose

Secondary: Mean Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

Secondary: Mean Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

Secondary: Percentage of Participants who Achieved Weight Loss ≥5%

Secondary: Percentage of Participants who Achieved Weight Loss ≥5%

Secondary: Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

Secondary: Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

Secondary: Rate of Hypoglycemia with Blood Glucose <54 milligram/deciliter (mg/dL) [<3.0 millimole/liter (mmol/L)] or Severe Hypoglycemia

Secondary: Rate of Hypoglycemia with Blood Glucose <54 milligram/deciliter (mg/dL) [<3.0 millimole/liter (mmol/L)] or Severe Hypoglycemia

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <5.7%

Secondary: Percentage of Participants Achieving an HbA1c Target Value of <5.7%

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients with Type 2 Diabetes (SURPASS-2)