SURPASS J-mono: A Study of Tirzepatide (LY3298176) Compared to Dulaglutide in Participants With Type 2 Diabetes

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03861052
• Collaborator: (none)
• Enrollment: 636
• Locations: 46
• Arms: 4
• Actual Duration (Months): 22.8
• Patients Per Site: 13.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The reason for this study is to see if the study drug tirzepatide (LY3298176) is effective and safe compared to dulaglutide in participants with type 2 diabetes in Japan.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Tirzepatide; Drug: Dulaglutide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 636 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study of Tirzepatide Monotherapy Compared to Dulaglutide 0.75 mg in Patients With Type 2 Diabetes Mellitus
• Actual Study Start Date: May 7, 2019
• Actual Primary Completion Date: Mar 10, 2021
• Actual Study Completion Date: Mar 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5 mg Tirzepatide Participants received 5 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 52 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: 10 mg Tirzepatide Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: 15 mg Tirzepatide Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Active Comparator: 0.75 mg Dulaglutide Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.	Drug: Dulaglutide; Administered SC; Other Names: LY2189265

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c (HbA1c) [Baseline, Week 52]

   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 for post-baseline measures: Variable = Baseline + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

Secondary Outcome Measures

1. Percentage of Participants With HbA1c of <7.0% [Week 52]

   HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

2. Change From Baseline in Fasting Serum Glucose [Baseline, Week 52]

   Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

3. Change From Baseline in Average 7-Point Self-Monitored Blood Glucose (SMBG) Values [Baseline, Week 52]

   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. LS mean was determined by analysis of covariance (ANCOVA) model for with Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment (Type III sum of squares) as variables.

4. Change From Baseline in Body Weight [Baseline, Week 52]

   Change from baseline in body weight. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

5. Percentage of Participants Who Achieve Weight Loss ≥5% From Baseline [Week 52]

   Percentage of participants who achieve weight loss ≥5% from baseline.

6. Change From Baseline in Fasting Insulin [Baseline, Week 52]

   Fasting Insulin is a test used to measure the amount of insulin in the body. LS mean was determined by MMRM model for post-baseline measures with log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

7. Change From Baseline in Fasting C-Peptide [Baseline, Week 52]

   Fasting C-peptide is a test used to measure the amount of C-peptide in the body. A high level of C-peptide can mean that body is making too much insulin. LS mean was determined by MMRM model for post-baseline measures: log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

8. Change From Baseline in Homeostasis Model Assessment B (HOMA-2B, Insulin) [Baseline, Week 52]

   HOMA-2B is an estimated steady state beta cell function based on updated HOMA2 model. The HOMA2 model estimates steady state pancreatic beta cell function (%B) as a percentage of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

9. Change From Baseline in HOMA-2S (Insluin) [Baseline, Week 52]

   HOMA2-S is an estimated insulin sensitivity based on updated HOMA2 model. The HOMA2 model is a computer model that estimates insulin sensitivity (%S) as percentages of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

10. Rate of Hypoglycemia With Glucose < 54 mg/dL or Severe Hypoglycemia [Baseline through Week 52]

    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 for post-baseline comparisons between treatment and control group: number of episodes = baseline hypoglycemia incidence + baseline BMI Group (<25 or >=25 kg/m^2) + washout of antidiabetic medication + baseline hemoglobin A1C (%) + treatment, with log (exposure in days/365.25) as an offset variable.

11. Number of Participants With Anti-Tirzepatide Antibodies [Baseline through Week 52]

    Number of participants with anti-tirzepatide antibodies. A participant is treatment emergent (TE) anti-drug antibody (ADA) evaluable if there is at least one non-missing test result for tirzepatide ADA for each of the baseline period and the postbaseline period. All percentages are relative to the total number of TE ADA evaluable participants in each treatment group. A TE ADA evaluable participant is considered to be TE ADA+ if the participant has at least one postbaseline titer that is a 4-fold or greater increase in titer from baseline measurement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Participant must:

• Have been diagnosed with type 2 diabetes mellitus based on the World Health Organization classification before the screening visit.

• Have HbA1c meeting the following criteria, as determined by the central laboratory at screening and baseline:

• for participants who are oral antihyperglycemic medication (OAM)-naïve at screening, ≥7.0% to ≤10.0% at both screening and baseline.

• for participants who have been taking OAM monotherapy at screening, ≥6.5% to ≤9.0% at screening, and ≥7.0% to ≤10.0% at baseline.

• Have body mass index (BMI) of ≥23 kilograms per meter squared at screening.

• Be of stable weight (±5%) during 3 months preceding screening; and agree to not initiate an intensive diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment.

Exclusion Criteria:

Participant must not:

• Have type 1 diabetes mellitus.

• Have had chronic or acute pancreatitis any time prior to study entry.

• Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring immediate or urgent treatment.

• Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss.

• Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level >3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range.

• Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months.

• Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2.

• Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical corporation THY Tokuyama Clinic	Chiba Mihama-ku	Chiba	Japan	261-0004
2	Akaicho Clinic	Chiba-shi	Chiba	Japan	260 0804
3	National Hospital Organization Kure Medical Center	Kure	Hiroshima	Japan	737-0023
4	Hasegawa Medical Clinic	Chitose	Hokkaido	Japan	066-0032
5	Yuri Ono Clinic	Sapporo	Hokkaido	Japan	060-0001
6	Watanabe Naika Clinic	Nishinomiya	Hyogo	Japan	662-0971
7	Hayashi Clinic	Nishinomiya	Hyogo	Japan	663-8113
8	Naka Memorial Clinic	Naka	Ibaraki	Japan	311-0113
9	Hayashi Diabetes Internal Medicine Clinic	Chigasaki-sh	Kanagawa	Japan	253-0044
10	Matoba Diabetes Clinic	Ebina	Kanagawa	Japan	243-0432
11	Takai Naika Clinic	Kamakura	Kanagawa	Japan	247-0056
12	Kanto Rosai Hospital	Kawasaki	Kanagawa	Japan	211-8510
13	H.E.C. Science Clinic	Yokohama	Kanagawa	Japan	235-0045
14	Medical Corporation Heishinkai OCROM Clinic	Suita-shi	Osaka	Japan	565-0853
15	Takatsuki Red Cross Hospital	Takatsuki	Osaka	Japan	569-1096
16	Senrichuo Ekimae Clinic	Toyonaka	Osaka	Japan	560-0082
17	Asano Clinic	Kawagoe	Saitama	Japan	350 0581
18	Kawaguchi General Hospital	Kawaguchi	Saitama	Japan	332-8558
19	Wakakusa Clinic	Shimotsuke	Tochigi	Japan	329-0433
20	Seiwa Clinic	Adachi-ku	Tokyo	Japan	123 0845
21	Meiwa Hospital	Chiyodaku	Tokyo	Japan	101 0041
22	HDC Atlas Clinic	Chiyoda	Tokyo	Japan	102-0082
23	Asahi Life Foundation Adult Disease Research Center	Chuo-ku	Tokyo	Japan	103 0002
24	Nihonbashi Sakura Clinic	Chuo-ku	Tokyo	Japan	103-0025
25	Tokyo-Eki Center-building Clinic	Chuo-ku	Tokyo	Japan	103-0027
26	Medical Corporation Chiseikai Tokyo Center Clinic	Chuo-ku	Tokyo	Japan	103-0028
27	Tokyo aSBo Clinic	Chuo-ku	Tokyo	Japan	104 0031
28	Fukuwa Clinic	Chuo-ku	Tokyo	Japan	104-0031
29	IHL Shinagawa East One Medical Clinic	Minato-ku	Tokyo	Japan	108-0075
30	Sato Medical Clinic	Ootaku	Tokyo	Japan	143-0015
31	Medical Corporation Heishinkai ToCROM Clinic	Shinjuku-ku	Tokyo	Japan	160 0008
32	Tomonaga Clinic	Shinjuku-ku	Tokyo	Japan	160 0022
33	Shinjuku Research Park Clinic	Shinjuku	Tokyo	Japan	169-0073
34	Shinei Clinic	Suginami	Tokyo	Japan	166-0003
35	Ikebukuro Metropolitan Clinic	Toshima-ku	Tokyo	Japan	171-0021
36	Futata Tetsuhiro Clinic	Fukuoka		Japan	810-0006
37	JR Hiroshima Hospital	Hiroshima		Japan	732-0057
38	Yoshimura Clinic	Kumamoto		Japan	861-8039
39	Keiseikai Kajiyama Clinic	Kyoto		Japan	6008898
40	Abe Clinic	Oita		Japan	870-0039
41	OKAYAMA Medical Center	Okayama		Japan	701-1192
42	AMC Nishiumeda Clinic	Osaka		Japan	530-0001
43	Kitada Clinic	Osaka		Japan	538-0044
44	Nanko Clinic	Osaka		Japan	559-0011
45	Suruga Clinic	Shizuoka		Japan	424-0855
46	Yokohama Minoru Clinic	Yokohama		Japan	232-0064

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol: Clinical Study Protocol Amendment Version (a) - Jan 17, 2019
• Study Protocol: Clinical Study Protocol Addendum Version (1) - Dec 18, 2018
• Statistical Analysis Plan: Statistical Analysis Plan Version 2 - Apr 7, 2021
• Statistical Analysis Plan: Statistical Analysis Plan Addendum Version 2 - Apr 7, 2021

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03861052
• Other Study ID Numbers: 17077; I8F-JE-GPGO
• First Posted: Mar 4, 2019
• Last Update Posted: Apr 14, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Dulaglutide; Tirzepatide

Study Results

Participant Flow

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks
Period Title: Overall Study
STARTED	159	158	160	159
Received at Least One Dose of Study Drug	159	158	160	159
COMPLETED	155	151	155	154
NOT COMPLETED	4	7	5	5

Baseline Characteristics

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide	Total
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks	Total of all reporting groups
Overall Participants	159	158	160	159	636
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	120 75.5%	123 77.8%	124 77.5%	111 69.8%	478 75.2%
>=65 years	39 24.5%	35 22.2%	36 22.5%	48 30.2%	158 24.8%
Sex: Female, Male (Count of Participants)
Female	46 28.9%	39 24.7%	28 17.5%	42 26.4%	155 24.4%
Male	113 71.1%	119 75.3%	132 82.5%	117 73.6%	481 75.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	159 100%	158 100%	160 100%	159 100%	636 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Japan	159 100%	158 100%	160 100%	159 100%	636 100%
Hemoglobin A1c [HbA1c] (percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of HbA1c]	8.18 (0.88)	8.19 (0.86)	8.19 (0.89)	8.15 (0.86)	8.18 (0.87)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c)
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 for post-baseline measures: Variable = Baseline + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks
Measure Participants	158	156	159	159
Least Squares Mean (Standard Error) [percentage of HbA1c]	-2.37 (0.066)	-2.55 (0.067)	-2.82 (0.066)	-1.29 (0.065)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.09
	Confidence Interval	(2-Sided) 95%; -1.27 to -0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.27
	Confidence Interval	(2-Sided) 95%; -1.45 to -1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.53
	Confidence Interval	(2-Sided) 95%; -1.71 to -1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With HbA1c of <7.0%
Description	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks
Measure Participants	158	156	159	159
Number [percentage of participants]	93.67 58.9%	96.79 61.3%	99.37 62.1%	67.30 42.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.89
	Confidence Interval	(2-Sided) 95%; 4.53 to 21.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	20.57
	Confidence Interval	(2-Sided) 95%; 7.73 to 54.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	85.31
	Confidence Interval	(2-Sided) 95%; 15.80 to 460.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Fasting Serum Glucose
Description	Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks..	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks
Measure Participants	158	156	159	159
Least Squares Mean (Standard Error) [milligrams per decilitre (mg/dL)]	-57.9 (1.73)	-64.6 (1.76)	-67.6 (1.75)	-31.9 (1.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-25.9
	Confidence Interval	(2-Sided) 95%; -30.7 to -21.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-32.7
	Confidence Interval	(2-Sided) 95%; -37.5 to -27.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-35.7
	Confidence Interval	(2-Sided) 95%; -40.6 to 30.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
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. LS mean was determined by analysis of covariance (ANCOVA) model for with Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment (Type III sum of squares) as variables.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 week	Participants received 10 mg tirzepatide administered SC once weekly for 52 week	Participants received 15 mg tirzepatide administered SC once weekly for 52 week	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks
Measure Participants	141	133	135	137
Least Squares Mean (Standard Error) [mg/dL]	-59.5 (1.46)	-64.2 (1.50)	-68.6 (1.50)	-42.2 (1.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-17.3
	Confidence Interval	(2-Sided) 95%; -21.4 to -13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-22.0
	Confidence Interval	(2-Sided) 95%; -26.1 to -17.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-26.4
	Confidence Interval	(2-Sided) 95%; -30.5 to -22.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	Change from baseline in body weight. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
Measure Participants	158	156	159	159
Least Squares Mean (Standard Error) [kilogram (kg)]	-5.8 (0.41)	-8.5 (0.42)	-10.7 (0.41)	-0.5 (0.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-5.2
	Confidence Interval	(2-Sided) 95%; -6.4 to -4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-7.9
	Confidence Interval	(2-Sided) 95%; -9.1 to -6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-10.1
	Confidence Interval	(2-Sided) 95%; -11.3 to -9.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants Who Achieve Weight Loss ≥5% From Baseline
Description	Percentage of participants who achieve weight loss ≥5% from baseline.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
Measure Participants	158	156	159	159
Number [percentage of participants]	60.76 38.2%	82.05 51.9%	89.31 55.8%	10.69 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	14.44
	Confidence Interval	(2-Sided) 95%; 7.88 to 26.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	44.96
	Confidence Interval	(2-Sided) 95%; 23.12 to 87.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	82.67
	Confidence Interval	(2-Sided) 95%; 39.84 to 171.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Fasting Insulin
Description	Fasting Insulin is a test used to measure the amount of insulin in the body. LS mean was determined by MMRM model for post-baseline measures with log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
Measure Participants	148	146	157	155
Least Squares Mean (Standard Error) [milliunits per litre (mU/L)]	-1.07 (0.374)	-1.87 (0.344)	-2.00 (0.335)	1.40 (0.482)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.47
	Confidence Interval	(2-Sided) 95%; -3.67 to -1.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.610
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.27
	Confidence Interval	(2-Sided) 95%; -4.43 to -2.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.592
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.40
	Confidence Interval	(2-Sided) 95%; -4.55 to -2.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.587
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Fasting C-Peptide
Description	Fasting C-peptide is a test used to measure the amount of C-peptide in the body. A high level of C-peptide can mean that body is making too much insulin. LS mean was determined by MMRM model for post-baseline measures: log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
Measure Participants	148	146	157	155
Least Squares Mean (Standard Error) [micrograms per liter (ug/L)]	-0.25 (0.045)	-0.39 (0.042)	-0.37 (0.042)	0.01 (0.052)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95%; -0.40 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.069
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.53 to -0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.067
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.51 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.067
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in Homeostasis Model Assessment B (HOMA-2B, Insulin)
Description	HOMA-2B is an estimated steady state beta cell function based on updated HOMA2 model. The HOMA2 model estimates steady state pancreatic beta cell function (%B) as a percentage of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
Measure Participants	146	137	147	153
Least Squares Mean (Standard Error) [percentage of insulin sensitivity]	38.5 (2.15)	43.0 (2.38)	46.3 (2.44)	22.4 (1.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	16.1
	Confidence Interval	(2-Sided) 95%; 10.7 to 21.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.72
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	20.6
	Confidence Interval	(2-Sided) 95%; 14.9 to 26.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.90
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	23.9
	Confidence Interval	(2-Sided) 95%; 18.1 to 29.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.95
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in HOMA-2S (Insluin)
Description	HOMA2-S is an estimated insulin sensitivity based on updated HOMA2 model. The HOMA2 model is a computer model that estimates insulin sensitivity (%S) as percentages of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
Measure Participants	146	137	147	153
Least Squares Mean (Standard Error) [percentage of insulin sensitivity]	14.5 (3.38)	21.6 (3.83)	25.7 (3.95)	-5.4 (2.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	19.9
	Confidence Interval	(2-Sided) 95%; 11.7 to 28.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.22
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	27.0
	Confidence Interval	(2-Sided) 95%; 18.0 to 36.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.59
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 0.75 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	31.2
	Confidence Interval	(2-Sided) 95%; 22.0 to 40.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.68
	Estimation Comments

11. Secondary Outcome

Title	Rate of Hypoglycemia With Glucose < 54 mg/dL or Severe Hypoglycemia
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 for post-baseline comparisons between treatment and control group: number of episodes = baseline hypoglycemia incidence + baseline BMI Group (<25 or >=25 kg/m^2) + washout of antidiabetic medication + baseline hemoglobin A1C (%) + treatment, with log (exposure in days/365.25) as an offset variable.
Time Frame	Baseline through Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks..	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks
Measure Participants	159	158	160	159
Number [Episodes/participant/365.25 days]	0	0	0.012	0

12. Secondary Outcome

Title	Number of Participants With Anti-Tirzepatide Antibodies
Description	Number of participants with anti-tirzepatide antibodies. A participant is treatment emergent (TE) anti-drug antibody (ADA) evaluable if there is at least one non-missing test result for tirzepatide ADA for each of the baseline period and the postbaseline period. All percentages are relative to the total number of TE ADA evaluable participants in each treatment group. A TE ADA evaluable participant is considered to be TE ADA+ if the participant has at least one postbaseline titer that is a 4-fold or greater increase in titer from baseline measurement.
Time Frame	Baseline through Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.	Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
Measure Participants	158	158	160	159
Number [participants]	97 61%	102 64.6%	123 76.9%	8 5%

Adverse Events

Time Frame	Baseline through Week 52
Adverse Event Reporting 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.
Arm/Group Title	5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide		0.75 mg Dulaglutide
Arm/Group Description	Participants received 5 mg tirzepatide administered SC once weekly for 52 weeks.		Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.		Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.		Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
All Cause Mortality
	5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide		0.75 mg Dulaglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/159 (0%)		0/158 (0%)		0/160 (0%)		0/159 (0%)
Serious Adverse Events
	5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide		0.75 mg Dulaglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/159 (5%)		10/158 (6.3%)		7/160 (4.4%)		14/159 (8.8%)
Cardiac disorders
Acute myocardial infarction	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Angina unstable	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Cardiac failure	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Myocardial infarction	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Eye disorders
Cataract	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Gastrointestinal disorders
Duodenal ulcer	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Gastric ulcer	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Gastric ulcer haemorrhage	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Inguinal hernia	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Large intestine polyp	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Rectal polyp	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Hepatobiliary disorders
Cholangitis	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Cholangitis acute	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Cholelithiasis	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Infections and infestations
Appendicitis	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Atypical pneumonia	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Covid-19 pneumonia	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Gastroenteritis	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Infectious pleural effusion	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Periodontitis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Pyelitis	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Sinusitis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Injury, poisoning and procedural complications
Acetabulum fracture	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Clavicle fracture	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Meniscus injury	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Pulmonary contusion	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Rib fracture	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Tendon rupture	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Upper limb fracture	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Vascular injury	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Investigations
Sars-cov-2 test positive	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Musculoskeletal and connective tissue disorders
Jaw cyst	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Lumbar spinal stenosis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebellopontine angle tumour	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Cholesteatoma	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Colon adenoma	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Lung neoplasm malignant	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Prostate cancer	0/113 (0%)	0	2/119 (1.7%)	2	0/132 (0%)	0	1/117 (0.9%)	1
Renal cell carcinoma	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Nervous system disorders
Facial paralysis	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Skin and subcutaneous tissue disorders
Dermatomyositis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Surgical and medical procedures
Percutaneous coronary intervention	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Other (Not Including Serious) Adverse Events
	5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide		0.75 mg Dulaglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	131/159 (82.4%)		121/158 (76.6%)		134/160 (83.8%)		120/159 (75.5%)
Blood and lymphatic system disorders
Anaemia	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Disseminated intravascular coagulation	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Iron deficiency anaemia	3/159 (1.9%)	3	2/158 (1.3%)	2	0/160 (0%)	0	0/159 (0%)	0
Leukocytosis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Normochromic normocytic anaemia	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Splenomegaly	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Cardiac disorders
Angina pectoris	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Arrhythmia	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Atrial fibrillation	2/159 (1.3%)	2	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Bundle branch block right	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Left ventricular hypertrophy	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Palpitations	2/159 (1.3%)	2	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Sinus bradycardia	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Sinus tachycardia	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Tachycardia	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Ventricular extrasystoles	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Ear and labyrinth disorders
Vertigo	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	2/159 (1.3%)	2
Endocrine disorders
Goitre	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Hyperthyroidism	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Thyroid mass	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Eye disorders
Asthenopia	1/159 (0.6%)	10	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Blepharitis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Cataract	1/159 (0.6%)	1	0/158 (0%)	0	3/160 (1.9%)	3	1/159 (0.6%)	1
Conjunctival deposit	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Conjunctival haemorrhage	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Conjunctivitis allergic	2/159 (1.3%)	2	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Corneal disorder	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Dark circles under eyes	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Diabetic retinopathy	0/159 (0%)	0	0/158 (0%)	0	3/160 (1.9%)	3	1/159 (0.6%)	1
Dry eye	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	4/159 (2.5%)	4
Glaucoma	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Keratitis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Ocular hypertension	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Optic disc haemorrhage	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Vitreous detachment	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Vitreous floaters	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	10/159 (6.3%)	35	11/158 (7%)	11	16/160 (10%)	89	4/159 (2.5%)	4
Abdominal distension	6/159 (3.8%)	6	4/158 (2.5%)	4	7/160 (4.4%)	8	2/159 (1.3%)	2
Abdominal pain	4/159 (2.5%)	5	2/158 (1.3%)	6	7/160 (4.4%)	10	3/159 (1.9%)	4
Abdominal pain lower	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Abdominal pain upper	1/159 (0.6%)	2	4/158 (2.5%)	4	4/160 (2.5%)	4	2/159 (1.3%)	2
Anal polyp	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Angular cheilitis	0/159 (0%)	0	2/158 (1.3%)	2	0/160 (0%)	0	0/159 (0%)	0
Barrett's oesophagus	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Cheilitis	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Chronic gastritis	0/159 (0%)	0	3/158 (1.9%)	3	1/160 (0.6%)	1	1/159 (0.6%)	1
Colitis	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Colitis ischaemic	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Constipation	24/159 (15.1%)	28	28/158 (17.7%)	34	22/160 (13.8%)	32	17/159 (10.7%)	21
Defaecation disorder	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Dental caries	2/159 (1.3%)	2	4/158 (2.5%)	4	1/160 (0.6%)	1	4/159 (2.5%)	4
Diarrhoea	27/159 (17%)	45	14/158 (8.9%)	27	18/160 (11.3%)	37	11/159 (6.9%)	20
Diverticulum intestinal	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Duodenal polyp	0/159 (0%)	0	0/158 (0%)	0	2/160 (1.3%)	2	0/159 (0%)	0
Duodenal ulcer	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Dyschezia	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Dyspepsia	9/159 (5.7%)	10	8/158 (5.1%)	9	10/160 (6.3%)	13	2/159 (1.3%)	2
Enterocolitis	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Epigastric discomfort	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Eructation	1/159 (0.6%)	1	0/158 (0%)	0	3/160 (1.9%)	3	0/159 (0%)	0
Faeces hard	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Faeces soft	1/159 (0.6%)	1	1/158 (0.6%)	1	3/160 (1.9%)	3	1/159 (0.6%)	3
Flatulence	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Food poisoning	2/159 (1.3%)	3	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Gastric polyps	1/159 (0.6%)	1	2/158 (1.3%)	2	0/160 (0%)	0	0/159 (0%)	0
Gastritis	2/159 (1.3%)	2	1/158 (0.6%)	1	3/160 (1.9%)	3	1/159 (0.6%)	1
Gastritis erosive	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Gastrointestinal disorder	1/159 (0.6%)	1	3/158 (1.9%)	3	2/160 (1.3%)	2	0/159 (0%)	0
Gastrointestinal motility disorder	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Gastrooesophageal reflux disease	1/159 (0.6%)	1	2/158 (1.3%)	2	7/160 (4.4%)	8	3/159 (1.9%)	3
Gingival swelling	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Glossitis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Haematochezia	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Haemorrhoidal haemorrhage	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Haemorrhoids	1/159 (0.6%)	1	2/158 (1.3%)	2	0/160 (0%)	0	0/159 (0%)	0
Hiatus hernia	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Hyperchlorhydria	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Intestinal pseudo-obstruction	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Irritable bowel syndrome	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Large intestine polyp	0/159 (0%)	0	3/158 (1.9%)	3	1/160 (0.6%)	1	1/159 (0.6%)	1
Lumbar hernia	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Nausea	19/159 (11.9%)	77	31/158 (19.6%)	67	32/160 (20%)	102	12/159 (7.5%)	13
Neurogenic bowel	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Oral pain	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Pancreatic duct dilatation	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Pancreatic enlargement	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Periodontal disease	1/159 (0.6%)	1	1/158 (0.6%)	1	1/160 (0.6%)	1	1/159 (0.6%)	1
Rectal polyp	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Stomatitis	3/159 (1.9%)	3	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Toothache	2/159 (1.3%)	2	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Vomiting	13/159 (8.2%)	16	8/158 (5.1%)	17	19/160 (11.9%)	40	2/159 (1.3%)	2
General disorders
Asthenia	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Chest discomfort	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Chest pain	0/159 (0%)	0	1/158 (0.6%)	1	2/160 (1.3%)	2	0/159 (0%)	0
Chills	1/159 (0.6%)	1	1/158 (0.6%)	1	1/160 (0.6%)	25	0/159 (0%)	0
Discomfort	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Fatigue	1/159 (0.6%)	1	0/158 (0%)	0	3/160 (1.9%)	3	0/159 (0%)	0
Feeling cold	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Hunger	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Hypothermia	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Induration	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Injection site bruising	1/159 (0.6%)	1	1/158 (0.6%)	2	1/160 (0.6%)	1	1/159 (0.6%)	1
Injection site eczema	0/159 (0%)	0	1/158 (0.6%)	22	0/160 (0%)	0	0/159 (0%)	0
Injection site erythema	1/159 (0.6%)	1	2/158 (1.3%)	43	3/160 (1.9%)	16	1/159 (0.6%)	15
Injection site hypersensitivity	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	3
Injection site induration	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	8
Injection site oedema	0/159 (0%)	0	1/158 (0.6%)	3	0/160 (0%)	0	0/159 (0%)	0
Injection site pruritus	2/159 (1.3%)	3	2/158 (1.3%)	46	3/160 (1.9%)	23	3/159 (1.9%)	46
Injection site rash	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	2	1/159 (0.6%)	4
Injection site reaction	2/159 (1.3%)	47	5/158 (3.2%)	44	9/160 (5.6%)	129	12/159 (7.5%)	80
Injection site swelling	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	2	1/159 (0.6%)	9
Malaise	3/159 (1.9%)	6	6/158 (3.8%)	12	3/160 (1.9%)	4	3/159 (1.9%)	5
Oedema peripheral	0/159 (0%)	0	1/158 (0.6%)	1	2/160 (1.3%)	2	0/159 (0%)	0
Pyrexia	1/159 (0.6%)	1	1/158 (0.6%)	2	3/160 (1.9%)	3	2/159 (1.3%)	3
Thirst	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Hepatobiliary disorders
Cholelithiasis	1/159 (0.6%)	1	0/158 (0%)	0	2/160 (1.3%)	2	0/159 (0%)	0
Gallbladder polyp	1/159 (0.6%)	1	0/158 (0%)	0	6/160 (3.8%)	6	0/159 (0%)	0
Hepatic cyst	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Hepatic function abnormal	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Hepatic mass	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Hepatic steatosis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Immune system disorders
Drug hypersensitivity	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Hypersensitivity	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Seasonal allergy	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	2	2/159 (1.3%)	2
Infections and infestations
Acute sinusitis	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Anal abscess	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Bronchitis	2/159 (1.3%)	2	2/158 (1.3%)	2	1/160 (0.6%)	1	1/159 (0.6%)	1
Cellulitis	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Conjunctivitis	1/159 (0.6%)	1	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Conjunctivitis bacterial	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Covid-19	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Cystitis	7/159 (4.4%)	7	1/158 (0.6%)	1	0/160 (0%)	0	2/159 (1.3%)	3
Dermatitis infected	1/159 (0.6%)	1	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Dermatophytosis of nail	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Diarrhoea infectious	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Empyema	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Enterocolitis infectious	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Folliculitis	2/159 (1.3%)	2	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Furuncle	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Gastroenteritis	9/159 (5.7%)	9	2/158 (1.3%)	2	7/160 (4.4%)	7	4/159 (2.5%)	5
Gastroenteritis norovirus	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Gingivitis	2/159 (1.3%)	2	2/158 (1.3%)	2	4/160 (2.5%)	4	0/159 (0%)	0
Helicobacter gastritis	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Helicobacter infection	1/159 (0.6%)	1	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Herpes simplex	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Herpes zoster	2/159 (1.3%)	2	4/158 (2.5%)	4	2/160 (1.3%)	2	4/159 (2.5%)	4
Hordeolum	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Infectious pleural effusion	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Influenza	1/159 (0.6%)	1	1/158 (0.6%)	1	1/160 (0.6%)	1	4/159 (2.5%)	4
Laryngitis	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Nasopharyngitis	29/159 (18.2%)	41	25/158 (15.8%)	28	22/160 (13.8%)	26	26/159 (16.4%)	30
Oral herpes	1/159 (0.6%)	1	2/158 (1.3%)	2	1/160 (0.6%)	2	1/159 (0.6%)	2
Otitis externa	2/159 (1.3%)	2	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Otitis media	0/159 (0%)	0	2/158 (1.3%)	2	0/160 (0%)	0	0/159 (0%)	0
Paronychia	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Parotitis	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Periodontitis	1/159 (0.6%)	1	2/158 (1.3%)	2	2/160 (1.3%)	3	1/159 (0.6%)	1
Pharyngitis	3/159 (1.9%)	3	7/158 (4.4%)	9	6/160 (3.8%)	6	7/159 (4.4%)	8
Pneumonia	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Purulence	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Pyelonephritis	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Sinusitis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Skin infection	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Tinea infection	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Tinea pedis	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Tonsillitis	1/159 (0.6%)	1	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Upper respiratory tract infection	5/159 (3.1%)	5	2/158 (1.3%)	2	3/160 (1.9%)	5	3/159 (1.9%)	3
Urinary tract infection	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Injury, poisoning and procedural complications
Ankle fracture	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Arthropod sting	1/159 (0.6%)	1	1/158 (0.6%)	1	1/160 (0.6%)	1	1/159 (0.6%)	1
Chillblains	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Contusion	1/159 (0.6%)	1	2/158 (1.3%)	2	5/160 (3.1%)	6	0/159 (0%)	0
Eye injury	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Eyelid injury	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Fall	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Foot fracture	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Heat stroke	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Joint dislocation	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Ligament injury	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Ligament rupture	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Ligament sprain	0/159 (0%)	0	2/158 (1.3%)	2	2/160 (1.3%)	2	0/159 (0%)	0
Limb injury	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Lip injury	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Lower limb fracture	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Meniscus injury	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Muscle strain	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Nasal injury	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Overdose	0/159 (0%)	0	0/158 (0%)	0	2/160 (1.3%)	2	1/159 (0.6%)	1
Skin abrasion	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Skin laceration	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Stab wound	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Thermal burn	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Tooth injury	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Upper limb fracture	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Wound	2/159 (1.3%)	2	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Wound complication	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Investigations
Alanine aminotransferase increased	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Amylase increased	8/159 (5%)	13	3/158 (1.9%)	3	5/160 (3.1%)	6	1/159 (0.6%)	2
Blood creatine phosphokinase increased	1/159 (0.6%)	1	3/158 (1.9%)	3	0/160 (0%)	0	0/159 (0%)	0
Blood insulin decreased	1/159 (0.6%)	2	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Blood pressure decreased	2/159 (1.3%)	2	0/158 (0%)	0	1/160 (0.6%)	2	0/159 (0%)	0
Blood pressure increased	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Blood triglycerides increased	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
C-reactive protein increased	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Carcinoembryonic antigen increased	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Eosinophil count increased	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Gamma-glutamyltransferase increased	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Haemoglobin decreased	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Heart rate increased	1/159 (0.6%)	5	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Hepatitis e antibody positive	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Insulin c-peptide decreased	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Lipase increased	12/159 (7.5%)	18	7/158 (4.4%)	7	10/160 (6.3%)	14	5/159 (3.1%)	7
Liver function test increased	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Nutritional condition abnormal	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Occult blood	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Occult blood positive	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Pancreatic enzymes increased	1/159 (0.6%)	1	0/158 (0%)	0	5/160 (3.1%)	5	3/159 (1.9%)	4
Red blood cell sedimentation rate increased	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Salmonella test positive	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	2	0/159 (0%)	0
Urine albumin/creatinine ratio increased	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Weight decreased	3/159 (1.9%)	3	2/158 (1.3%)	2	5/160 (3.1%)	5	0/159 (0%)	0
Weight increased	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Metabolism and nutrition disorders
Decreased appetite	22/159 (13.8%)	25	21/158 (13.3%)	31	35/160 (21.9%)	107	7/159 (4.4%)	7
Dehydration	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Gout	2/159 (1.3%)	2	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Hyperglycaemia	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	2	9/159 (5.7%)	9
Hyperlipasaemia	3/159 (1.9%)	4	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Hyperuricaemia	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Hypokalaemia	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/159 (1.3%)	2	3/158 (1.9%)	3	3/160 (1.9%)	3	3/159 (1.9%)	3
Arthritis	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Back pain	8/159 (5%)	8	5/158 (3.2%)	5	9/160 (5.6%)	10	7/159 (4.4%)	8
Fasciitis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	2
Intervertebral disc protrusion	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Muscle spasms	2/159 (1.3%)	3	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Musculoskeletal stiffness	0/159 (0%)	0	1/158 (0.6%)	1	2/160 (1.3%)	2	0/159 (0%)	0
Myalgia	1/159 (0.6%)	1	1/158 (0.6%)	1	3/160 (1.9%)	3	2/159 (1.3%)	2
Neck pain	1/159 (0.6%)	1	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Osteoarthritis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Osteoporosis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Pain in extremity	0/159 (0%)	0	1/158 (0.6%)	1	3/160 (1.9%)	3	0/159 (0%)	0
Periarthritis	3/159 (1.9%)	3	2/158 (1.3%)	2	4/160 (2.5%)	4	3/159 (1.9%)	3
Rheumatoid arthritis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Spinal osteoarthritis	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	3/159 (1.9%)	3
Spondylolisthesis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Synovial cyst	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Tendonitis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Tenosynovitis	0/159 (0%)	0	2/158 (1.3%)	2	0/160 (0%)	0	1/159 (0.6%)	1
Trigger finger	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal neoplasm	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Benign neoplasm of skin	1/159 (0.6%)	2	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Colon adenoma	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Intraductal papillary mucinous neoplasm	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Parathyroid tumour benign	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Prostate cancer	0/113 (0%)	0	1/119 (0.8%)	1	0/132 (0%)	0	0/117 (0%)	0
Skin papilloma	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Nervous system disorders
Carpal tunnel syndrome	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Cerebral infarction	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Cervicobrachial syndrome	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Dizziness	2/159 (1.3%)	13	4/158 (2.5%)	4	7/160 (4.4%)	8	2/159 (1.3%)	2
Dizziness postural	1/159 (0.6%)	1	2/158 (1.3%)	2	3/160 (1.9%)	3	1/159 (0.6%)	1
Dysgeusia	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Facial paralysis	1/159 (0.6%)	1	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Head discomfort	1/159 (0.6%)	8	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Headache	8/159 (5%)	32	8/158 (5.1%)	15	2/160 (1.3%)	4	6/159 (3.8%)	8
Hypoaesthesia	2/159 (1.3%)	2	2/158 (1.3%)	2	1/160 (0.6%)	1	0/159 (0%)	0
Loss of consciousness	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Migraine	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Multiple system atrophy	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Neuralgia	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Paraesthesia	0/159 (0%)	0	2/158 (1.3%)	12	1/160 (0.6%)	1	0/159 (0%)	0
Patient elopement	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	2	0/159 (0%)	0
Sciatica	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Sensory disturbance	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Somnolence	1/159 (0.6%)	2	1/158 (0.6%)	1	0/160 (0%)	0	2/159 (1.3%)	2
Taste disorder	2/159 (1.3%)	2	2/158 (1.3%)	2	2/160 (1.3%)	2	0/159 (0%)	0
Trigeminal neuralgia	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	2	0/159 (0%)	0
Product Issues
Device physical property issue	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Psychiatric disorders
Depressed mood	2/159 (1.3%)	2	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Insomnia	2/159 (1.3%)	2	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	3
Renal and urinary disorders
Calculus urinary	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Diabetic nephropathy	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Dysuria	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Haematuria	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Nephrolithiasis	0/159 (0%)	0	0/158 (0%)	0	2/160 (1.3%)	2	0/159 (0%)	0
Pollakiuria	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Polyuria	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Renal cyst	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	1/159 (0.6%)	1
Renal impairment	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Ureterolithiasis	2/159 (1.3%)	2	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Urinary retention	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/113 (0%)	0	0/119 (0%)	0	1/132 (0.8%)	1	1/117 (0.9%)	1
Dysmenorrhoea	0/46 (0%)	0	0/39 (0%)	0	0/28 (0%)	0	1/42 (2.4%)	1
Erectile dysfunction	0/113 (0%)	0	1/119 (0.8%)	1	1/132 (0.8%)	1	0/117 (0%)	0
Ovarian cyst	0/46 (0%)	0	0/39 (0%)	0	1/28 (3.6%)	1	0/42 (0%)	0
Prostatitis	1/113 (0.9%)	1	0/119 (0%)	0	0/132 (0%)	0	0/117 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Cough	0/159 (0%)	0	3/158 (1.9%)	3	0/160 (0%)	0	2/159 (1.3%)	2
Dyspnoea	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Dyspnoea exertional	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Epistaxis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	2	2/159 (1.3%)	3
Hiccups	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Hyperventilation	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Interstitial lung disease	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Nasal inflammation	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Oropharyngeal discomfort	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Oropharyngeal pain	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	2/159 (1.3%)	2
Pneumonia aspiration	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Productive cough	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Rhinitis allergic	1/159 (0.6%)	1	1/158 (0.6%)	1	2/160 (1.3%)	2	0/159 (0%)	0
Rhinorrhoea	1/159 (0.6%)	1	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Throat tightness	1/159 (0.6%)	16	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Upper respiratory tract inflammation	3/159 (1.9%)	3	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Skin and subcutaneous tissue disorders
Acne	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Asteatosis	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Cold sweat	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Dermal cyst	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Dermatitis	1/159 (0.6%)	1	1/158 (0.6%)	1	1/160 (0.6%)	1	1/159 (0.6%)	1
Dermatitis atopic	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Dermatitis contact	4/159 (2.5%)	4	1/158 (0.6%)	1	1/160 (0.6%)	1	1/159 (0.6%)	1
Dermatomyositis	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Dry skin	0/159 (0%)	0	3/158 (1.9%)	3	1/160 (0.6%)	1	1/159 (0.6%)	1
Eczema	1/159 (0.6%)	1	4/158 (2.5%)	4	5/160 (3.1%)	5	4/159 (2.5%)	4
Eczema asteatotic	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	2/159 (1.3%)	2
Erythema	0/159 (0%)	0	1/158 (0.6%)	1	2/160 (1.3%)	15	1/159 (0.6%)	3
Haemorrhage subcutaneous	1/159 (0.6%)	3	1/158 (0.6%)	1	0/160 (0%)	0	1/159 (0.6%)	1
Hand dermatitis	0/159 (0%)	0	1/158 (0.6%)	1	1/160 (0.6%)	1	1/159 (0.6%)	1
Miliaria	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Onychoclasis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Palmoplantar keratoderma	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Pruritus	1/159 (0.6%)	1	5/158 (3.2%)	5	2/160 (1.3%)	2	2/159 (1.3%)	4
Rash	1/159 (0.6%)	1	2/158 (1.3%)	2	1/160 (0.6%)	1	1/159 (0.6%)	1
Rash pruritic	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Sensitive skin	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Urticaria	5/159 (3.1%)	7	2/158 (1.3%)	2	4/160 (2.5%)	4	0/159 (0%)	0
Surgical and medical procedures
Cataract operation	1/159 (0.6%)	1	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Coronary arterial stent insertion	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Inguinal hernia repair	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	0/159 (0%)	0
Large intestinal polypectomy	1/159 (0.6%)	1	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Open reduction of fracture	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Percutaneous coronary intervention	1/159 (0.6%)	1	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Tooth extraction	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Vascular disorders
Arteriosclerosis	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	1/159 (0.6%)	1
Hypertension	2/159 (1.3%)	2	1/158 (0.6%)	1	0/160 (0%)	0	5/159 (3.1%)	5
Hypotension	0/159 (0%)	0	1/158 (0.6%)	1	4/160 (2.5%)	4	0/159 (0%)	0
Internal haemorrhage	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1
Orthostatic hypotension	0/159 (0%)	0	0/158 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Peripheral coldness	0/159 (0%)	0	1/158 (0.6%)	1	0/160 (0%)	0	0/159 (0%)	0
Shock	0/159 (0%)	0	0/158 (0%)	0	0/160 (0%)	0	1/159 (0.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.