A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes (SURPASS-2)

• ClinicalTrials.gov Identifier: NCT03987919
• Recruitment Status: Completed
• First Posted: June 17, 2019
• Results First Posted: February 14, 2022
• Last Update Posted: February 14, 2022
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Type 2 Diabetes
• Interventions: Drug: Tirzepatide; Drug: Semaglutide
• Enrollment: 1879

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description	5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg semaglutide administered SC once a week.
Period Title: Overall Study
Started	471	469	470	469
Received at Least One Dose of Study Drug	470	469	470	469
Completed	452	442	446	443
Not Completed	19	27	24	26
Reason Not Completed
Adverse Event	1	4	1	3
Death	4	4	4	1
Lost to Follow-up	5	6	8	12
Physician Decision	0	2	0	4
Pregnancy	1	0	1	1
Protocol Violation	0	1	0	0
Site terminated by Sponsor	0	0	0	1
Withdrawal by Subject	7	7	8	4
Other - as reported by the investigator	1	3	2	0

Baseline Characteristics

Arm/Group Title		5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide	Total
Arm/Group Description		5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg semaglutide administered SC once a week.	Total of all reporting groups
Overall Number of Baseline Participants		470	469	470	469	1878
Baseline Analysis Population Description		All randomized participants who received at least one dose of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	470 participants	469 participants	470 participants	469 participants	1878 participants
		56.3 (10.0)	57.2 (10.5)	55.9 (10.4)	56.9 (10.8)	56.6 (10.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	470 participants	469 participants	470 participants	469 participants	1878 participants
	Female	265	231	256	244	996
	Male	205	238	214	225	882
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	470 participants	469 participants	470 participants	469 participants	1878 participants
	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); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	470 participants	469 participants	470 participants	469 participants	1878 participants
	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; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	470 participants	469 participants	470 participants	469 participants	1878 participants
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 [1]; Mean (Standard Deviation); Unit of measure: Percentage of HbA1c
	Number Analyzed	470 participants	469 participants	470 participants	469 participants	1878 participants
		8.32 (1.08)	8.30 (1.02)	8.26 (1.00)	8.25 (1.01)	8.28 (1.03)
		[1] Measure Description: HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
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).
Time Frame	Baseline, Week 40

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg semaglutide administered SC once a week.
Overall Number of Participants Analyzed	459	464	461
Least Squares Mean (Standard Error); Unit of Measure: Percentage of HbA1c
	-2.37 (0.048)	-2.46 (0.048)	-1.86 (0.048)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -0.64 to -0.38
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -0.73 to -0.47
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change From Baseline in HbA1c (5 mg)
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).
Time Frame	Baseline, Week 40

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	5 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:	5 mg tirzepatide administered SC once a week.	1 mg semaglutide administered SC once a week.
Overall Number of Participants Analyzed	461	461
Least Squares Mean (Standard Error); Unit of Measure: Percentage of HbA1c
	-2.09 (0.047)	-1.86 (0.048)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.36 to -0.10
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change From Baseline in Body Weight
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).
Time Frame	Baseline, Week 40

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:	5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg of semaglutide administered SC once a week.
Overall Number of Participants Analyzed	461	459	464	462
Least Squares Mean (Standard Error); Unit of Measure: Kilograms (kg)
	-7.8 (0.33)	-10.3 (0.34)	-12.4 (0.34)	-6.2 (0.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.6 to -0.7
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -5.0 to -3.2
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.2
	Confidence Interval	(2-Sided) 95%; -7.1 to -5.3
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants Achieving an HbA1c Target Value of <7%
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.
Time Frame	Week 40

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:	5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg semaglutide administered SC once a week.
Overall Number of Participants Analyzed	461	459	464	461
Measure Type: Number; Unit of Measure: Percentage of Participants
	85.47	88.89	92.24	81.13

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.023
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.54
	Confidence Interval	(2-Sided) 95%; 1.06 to 2.23
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.14
	Confidence Interval	(2-Sided) 95%; 1.44 to 3.17
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.03
	Confidence Interval	(2-Sided) 95%; 1.97 to 4.66
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline in Fasting Serum Glucose (FSG)
Description	Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. 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).
Time Frame	Baseline, Week 40

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:	5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg semaglutide administered SC once a week.
Overall Number of Participants Analyzed	461	458	464	459
Least Squares Mean (Standard Error); Unit of Measure: milligram per Deciliter (mg/dL)
	-56.0 (1.57)	-61.6 (1.60)	-63.4 (1.59)	-48.6 (1.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.3
	Confidence Interval	(2-Sided) 95%; -11.7 to -3.0
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.0
	Confidence Interval	(2-Sided) 95%; -17.4 to -8.6
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-14.7
	Confidence Interval	(2-Sided) 95%; -19.1 to -10.3
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Mean Change From Baseline in Daily 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. 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).
Time Frame	Baseline, Week 40

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:	5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg of semaglutide administered SC once a week.
Overall Number of Participants Analyzed	424	412	413	414
Least Squares Mean (Standard Error); Unit of Measure: mg/dL
	-65.4 (1.04)	-70.6 (1.05)	-74.3 (1.05)	-61.4 (1.04)

7. Secondary Outcome

Title	Percentage of Participants Who Achieved Weight Loss ≥5%
Description	Percentage of Participants who Achieved Weight Loss ≥5%.
Time Frame	Week 40

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:	5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg of semaglutide administered SC once a week.
Overall Number of Participants Analyzed	461	459	464	462
Measure Type: Number; Unit of Measure: Percentage of Participants
	68.55	82.35	86.21	58.44

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.58
	Confidence Interval	(2-Sided) 95%; 1.20 to 2.08
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.49
	Confidence Interval	(2-Sided) 95%; 2.57 to 4.75
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.60
	Confidence Interval	(2-Sided) 95%; 3.32 to 6.38
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score
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).
Time Frame	Baseline, Week 40

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug. Last observation carried forward (LOCF) endpoint only carries forward the last non-baseline observations before rescue therapy or stopping study drug.

Arm/Group Title		5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:		5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg of semaglutide administered SC once a week.
Overall Number of Participants Analyzed		419	399	398	412
Least Squares Mean (Standard Error); Unit of Measure: Units on a Scale
Hyperglycemia	Number Analyzed	418 participants	399 participants	398 participants	411 participants
		-1.3 (0.10)	-1.4 (0.10)	-1.5 (0.10)	-1.1 (0.10)
Hypoglycemia	Number Analyzed	416 participants	398 participants	398 participants	412 participants
		-0.7 (0.10)	-0.7 (0.10)	-0.8 (0.10)	-0.7 (0.10)
Total Score	Number Analyzed	419 participants	399 participants	398 participants	411 participants
		15.7 (0.18)	15.6 (0.19)	16.1 (0.19)	15.8 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	Hyperglycemia
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.084
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.50 to 0.03
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	Hyperglycemia
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.050
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.54 to 0.00
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	Hyperglycemia
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.005
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.66 to -0.12
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	Hypoglycemia
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.688
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.22
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	Hypoglycemia
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.909
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.26
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	Hypoglycemia
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.358
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.15
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	Total Score
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.701
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.62 to 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	Total Score
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.341
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.78 to 0.27
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	Total Score
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.321
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.79
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] 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: number of episodes = Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment.
Time Frame	Baseline through Safety Follow-Up (Up to Week 44)

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	1 mg Semaglutide
Arm/Group Description:	5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg of semaglutide administered SC once a week.
Overall Number of Participants Analyzed	470	469	470	469
Mean (Standard Error); Unit of Measure: Episodes/participant/365.25 days
	0.0102 (0.00423)	0.0046 (0.00488)	0.0202 (0.00840)	0.0046 (0.00340)

10. Secondary Outcome

Title	Percentage of Participants Achieving an HbA1c Target Value of <5.7%
Description	Percentage of Participants Achieving an HbA1c Target Value of <5.7%.
Time Frame	Week 40

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1 mg Semaglutide
Arm/Group Description:	5 mg tirzepatide administered SC once a week.	10 mg tirzepatide administered SC once a week.	15 mg tirzepatide administered SC once a week.	1 mg of semaglutide administered SC once a week.
Overall Number of Participants Analyzed	461	459	464	461
Measure Type: Number; Unit of Measure: Percentage of Participants
	29.28	44.66	50.86	19.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	5 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.86
	Confidence Interval	(2-Sided) 95%; 1.35 to 2.57
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	10 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.94
	Confidence Interval	(2-Sided) 95%; 2.88 to 5.39
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	15 mg Tirzepatide, 1 mg Semaglutide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.10
	Confidence Interval	(2-Sided) 95%; 3.73 to 6.97
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Baseline, Safety follow-up (44 Weeks)
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		1 mg Semaglutide
Arm/Group Description	5 mg tirzepatide administered subcutaneously (SC) once a week.		10 mg tirzepatide administered SC once a week.		15 mg tirzepatide administered SC once a week.		1 mg of semaglutide administered SC once a week.
All-Cause Mortality
	5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide		1 mg Semaglutide
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	4/470 (0.85%)		4/469 (0.85%)		4/470 (0.85%)		1/469 (0.21%)
Serious Adverse Events
	5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide		1 mg Semaglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/470 (7.02%)		25/469 (5.33%)		27/470 (5.74%)		13/469 (2.77%)
Blood and lymphatic system disorders
Anaemia † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Cardiac disorders
Acute myocardial infarction † 1	2/470 (0.43%)	3	0/469 (0.00%)	0	2/470 (0.43%)	2	0/469 (0.00%)	0
Angina unstable † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Atrial fibrillation † 1	2/470 (0.43%)	4	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Atrial flutter † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Cardiac failure † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Cardio-respiratory arrest † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Coronary artery disease † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Ventricular tachycardia † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Endocrine disorders
Acromegaly † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Eye disorders
Retinal vein occlusion † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Abdominal pain upper † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Constipation † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Epiploic appendagitis † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Gastrointestinal haemorrhage † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Inguinal hernia, obstructive † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Irritable bowel syndrome † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Lower gastrointestinal haemorrhage † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Nausea † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Strangulated umbilical hernia † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Vomiting † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
General disorders
Chest pain † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	1/470 (0.21%)	1	0/469 (0.00%)	0
Death † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Pyrexia † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Sudden death † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Hepatobiliary disorders
Cholecystitis acute † 1	1/470 (0.21%)	1	2/469 (0.43%)	2	2/470 (0.43%)	2	0/469 (0.00%)	0
Infections and infestations
Appendicitis † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Bacteraemia † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	1/469 (0.21%)	1
Cellulitis † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Cholecystitis infective † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Complicated appendicitis † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Covid-19 † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	1/469 (0.21%)	1
Covid-19 pneumonia † 1	2/470 (0.43%)	2	2/469 (0.43%)	2	2/470 (0.43%)	2	4/469 (0.85%)	4
Dengue fever † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Epididymitis † 1	1/205 (0.49%)	1	0/238 (0.00%)	0	0/214 (0.00%)	0	0/225 (0.00%)	0
Escherichia bacteraemia † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Lower respiratory tract infection † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Osteomyelitis † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Pharyngeal abscess † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Pneumonia † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	1/470 (0.21%)	1	1/469 (0.21%)	1
Pyelonephritis † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Sepsis † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Suspected covid-19 † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Urinary tract infection † 1	0/470 (0.00%)	0	2/469 (0.43%)	2	0/470 (0.00%)	0	0/469 (0.00%)	0
Urosepsis † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Injury, poisoning and procedural complications
Ankle fracture † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Femur fracture † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Hip fracture † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Intentional overdose † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Ligament injury † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Multiple injuries † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Traumatic amputation † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Upper limb fracture † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Wrist fracture † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Investigations
Amylase increased † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Coronavirus test positive † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Lipase increased † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Metabolism and nutrition disorders
Dehydration † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Hypoglycaemia † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Hyponatraemia † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Osteoarthritis † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Endometrial adenocarcinoma † 1	1/265 (0.38%)	1	0/231 (0.00%)	0	0/256 (0.00%)	0	0/244 (0.00%)	0
Glioblastoma multiforme † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Lung carcinoma cell type unspecified stage iii † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Metastatic squamous cell carcinoma † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Non-hodgkin's lymphoma † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Renal cell carcinoma † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Squamous cell carcinoma of skin † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Uterine leiomyoma † 1	0/265 (0.00%)	0	0/231 (0.00%)	0	1/256 (0.39%)	1	0/244 (0.00%)	0
Uterine neoplasm † 1	1/265 (0.38%)	1	0/231 (0.00%)	0	0/256 (0.00%)	0	0/244 (0.00%)	0
Nervous system disorders
Cerebellar infarction † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Cerebrovascular accident † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	2/470 (0.43%)	2	0/469 (0.00%)	0
Headache † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Ischaemic stroke † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Syncope † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	1/470 (0.21%)	1	0/469 (0.00%)	0
Psychiatric disorders
Post-traumatic stress disorder † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Suicide attempt † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
End stage renal disease † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Nephrolithiasis † 1	1/470 (0.21%)	1	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Urinary tract obstruction † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Reproductive system and breast disorders
Metrorrhagia † 1	1/265 (0.38%)	1	0/231 (0.00%)	0	0/256 (0.00%)	0	0/244 (0.00%)	0
Uterine prolapse † 1	0/265 (0.00%)	0	0/231 (0.00%)	0	0/256 (0.00%)	0	1/244 (0.41%)	1
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Chronic obstructive pulmonary disease † 1	0/470 (0.00%)	0	1/469 (0.21%)	1	0/470 (0.00%)	0	0/469 (0.00%)	0
Dyspnoea † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Pleural effusion † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Pulmonary embolism † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Respiratory failure † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Skin and subcutaneous tissue disorders
Diabetic ulcer † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Surgical and medical procedures
Abdominal hernia repair † 1	1/470 (0.21%)	1	0/469 (0.00%)	0	0/470 (0.00%)	0	0/469 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Hypertension † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Orthostatic hypotension † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	1/470 (0.21%)	1	0/469 (0.00%)	0
Peripheral vascular disorder † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
Venous thrombosis limb † 1	0/470 (0.00%)	0	0/469 (0.00%)	0	0/470 (0.00%)	0	1/469 (0.21%)	1
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide		1 mg Semaglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	170/470 (36.17%)		187/469 (39.87%)		202/470 (42.98%)		172/469 (36.67%)
Gastrointestinal disorders
Abdominal pain † 1	14/470 (2.98%)	16	20/469 (4.26%)	25	24/470 (5.11%)	30	24/469 (5.12%)	29
Constipation † 1	31/470 (6.60%)	35	21/469 (4.48%)	23	21/470 (4.47%)	23	27/469 (5.76%)	32
Diarrhoea † 1	62/470 (13.19%)	120	77/469 (16.42%)	98	65/470 (13.83%)	102	54/469 (11.51%)	68
Dyspepsia † 1	34/470 (7.23%)	46	29/469 (6.18%)	43	43/470 (9.15%)	51	31/469 (6.61%)	42
Nausea † 1	82/470 (17.45%)	110	90/469 (19.19%)	121	104/470 (22.13%)	136	84/469 (17.91%)	126
Vomiting † 1	27/470 (5.74%)	35	39/469 (8.32%)	54	46/470 (9.79%)	61	39/469 (8.32%)	53
Metabolism and nutrition disorders
Decreased appetite † 1	35/470 (7.45%)	38	34/469 (7.25%)	43	42/470 (8.94%)	51	25/469 (5.33%)	26
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment

Limitations and 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.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979
• EMail: ClinicalTrials.gov@lilly.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ten Doesschate T, van der Vaart TW, Debisarun PA, Taks E, Moorlag SJCFM, Paternotte N, Boersma WG, Kuiper VP, Roukens AHE, Rijnders BJA, Voss A, Veerman KM, Kerckhoffs APM, Oever JT, van Crevel R, van Nieuwkoop C, Lalmohamed A, van de Wijgert JHHM, Netea MG, Bonten MJM, van Werkhoven CH. Bacillus Calmette-Guerin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial. Clin Microbiol Infect. 2022 Sep;28(9):1278-1285. doi: 10.1016/j.cmi.2022.04.009. Epub 2022 Apr 28.

Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022 Mar;28(3):591-598. doi: 10.1038/s41591-022-01707-4. Epub 2022 Feb 24.

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• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03987919
• Other Study ID Numbers: 17001; I8F-MC-GPGL ( Other Identifier: Eli Lilly and Company ); 2018-004422-29 ( EudraCT Number )
• First Submitted: June 14, 2019
• First Posted: June 17, 2019
• Results First Submitted: January 21, 2022
• Results First Posted: February 14, 2022
• Last Update Posted: February 14, 2022