A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03131687
• Collaborator: (none)
• Enrollment: 318
• Locations: 49
• Arms: 6
• Actual Duration (Months): 14.3
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of the study drug tirzepatide in participants with type 2 diabetes mellitus.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: tirzepatide; Drug: Dulaglutide; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 318 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Once-Weekly LY3298176 Compared With Placebo and Dulaglutide in Patients With Type 2 Diabetes Mellitus
• Actual Study Start Date: May 24, 2017
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	Drug: Placebo; Administered SC
Experimental: 1 mg Tirzepatide 1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	Drug: tirzepatide; Administered SC; Other Names: LY3298176 ; Drug: Placebo; Administered SC
Experimental: 5 mg Tirzepatide 5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	Drug: tirzepatide; Administered SC; Other Names: LY3298176 ; Drug: Placebo; Administered SC
Experimental: 10 mg Tirzepatide 10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	Drug: tirzepatide; Administered SC; Other Names: LY3298176 ; Drug: Placebo; Administered SC
Experimental: 15 mg Tirzepatide 15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	Drug: tirzepatide; Administered SC; Other Names: LY3298176 ; Drug: Placebo; Administered SC
Active Comparator: 1.5 mg Dulaglutide 1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.	Drug: Dulaglutide; Administered SC; Other Names: LY2189265 ; Drug: Placebo; Administered SC

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response [Baseline, Week 26]

   HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. The Least Squares Mean is Posterior mean.

Secondary Outcome Measures

1. Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response [Baseline, Week 12]

   HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. The Least Squares Mean is Posterior mean.

2. Change From Baseline to Week 26 in HbA1c [Baseline, Week 26]

   HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: Baseline + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.

3. Change From Baseline to Week 12 in HbA1c [Baseline, Week 12]

   HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: Baseline + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.

4. Change From Baseline in Body Weight [Baseline, Week 26]

   Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with independent variables: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.

5. Percentage of Participants With 5% or Greater Body Weight Loss From Baseline [Week 26]

   Percentage of participants with 5% or greater body weight loss from baseline last observation carried forward (LOCF) analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors.

6. Percentage of Participants With 10% or Greater Body Weight Loss From Baseline [Week 26]

   Percentage of participants with 10% or greater body weight loss from baseline LOCF analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors.

7. Percentage of Participants Reaching the HbA1c Target of ≤6.5% [Week 26]

   Percentage of participants with HbA1c ≤6.5% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors.

8. Percentage of Participants Reaching the HbA1c Target of <7.0% [Week 26]

   Percentage of participants with HbA1c <7.0% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors.

9. Change From Baseline in Fasting Blood Glucose [Baseline, Week 26]

   Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.

10. Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) [Baseline, Week 26]

    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag,Treatment, time, treatment*time.

11. Change From Baseline in Total Cholesterol [Baseline, Week 26]

    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.

12. Change From Baseline in Triglycerides [Baseline, Week 26]

    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.

13. Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) [Baseline, Week 26]

    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.

14. Change From Baseline in Waist Circumference [Baseline, Week 26]

    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.

15. Number of Participants With Anti-Drug Antibodies [Baseline through Week 30]

    Number of Participants With Anti-Drug Antibodies.

16. Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide [Predose: Week 1,8,12 and 26; Postdose: Week 1,2,4 and 12]

    Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have had type 2 diabetes (T2D) for ≥6 months according to the World Health Organization (WHO) classification.

• Have HbA1c of 7.0% to 10.5%, inclusive, as assessed by the central laboratory.

• If on metformin, have been treated with stable doses of metformin for at least 3 months.

• Have a body mass index (BMI) ≥23 and <50 kilograms per square meter.

Exclusion Criteria:

• Have type 1 diabetes (T1D).

• Have used any glucose-lowering medication other than metformin within 3 months prior to study entry or during screening/lead-in period or have used any glucagon-like peptide-1 receptor agonists (GLP-1 RAs) at any time in the past.

• Have had any of the following cardiovascular conditions: acute myocardial infarction (MI), New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident (stroke).

• Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level

2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial.

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

• Have an estimated glomerular filtration rate (eGFR) <45 milliliters/minute/1.73 square meter, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation.

• Have serum calcitonin ≥20 picograms per milliliter, as determined by the central laboratory at study entry.

• Have any condition that is a contraindication for use of the GLP-1 RA class (per country-specific labels) at study entry or develop such condition between study entry and randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Internal Medicine Center LLC	Mobile	Alabama	United States	36608
2	Anaheim Clinical Trails	Anaheim	California	United States	92801
3	Valley Research	Fresno	California	United States	93720
4	National Research Institute	Huntington Park	California	United States	90255
5	National Research Institute	Los Angeles	California	United States	90057
6	Catalina Research Institute	Montclair	California	United States	91763
7	Valley Clinical Trails, Inc	Northridge	California	United States	91325
8	Artemis Institute For Clinical Research	San Diego	California	United States	92103
9	Artemis Institute For Clinical Research	San Marcos	California	United States	92078
10	Encompass Clinical Research	Spring Valley	California	United States	91978
11	University Clinical Investigators INC	Tustin	California	United States	92780
12	Chase Medical Research	Waterbury	Connecticut	United States	06708
13	Clinical Research of South Florida	Coral Gables	Florida	United States	33134
14	East Coast Institute For Research	Jacksonville	Florida	United States	32216
15	Suncoast Research Group, LCC	Miami	Florida	United States	33135
16	New Horizon Research Center	Miami	Florida	United States	33175
17	Sensible Healthcare	Ocoee	Florida	United States	34761
18	Palm Harbor Medical Associate	Palm Harbor	Florida	United States	34684
19	Solaris Clinical Research	Meridian	Idaho	United States	83646
20	Iderc P.L.C.	West Des Moines	Iowa	United States	50265
21	Cotton O'Neil Diabetes and Endocrine	Topeka	Kansas	United States	66606
22	ActivMed Practices & Research	Methuen	Massachusetts	United States	01844
23	Clinical Research Professionals	Saint Louis	Missouri	United States	63141
24	Palm Research Center	Las Vegas	Nevada	United States	89128
25	Premier Research	Trenton	New Jersey	United States	08611
26	Manhattan Medical Research	New York	New York	United States	10016
27	Lillestol Research LLC	Fargo	North Dakota	United States	58103
28	Aventiv Research	Columbus	Ohio	United States	43213
29	The Corvallis Clinic P.C.	Corvallis	Oregon	United States	97330
30	PMG Research Of Charleston LLC	Moncks Corner	South Carolina	United States	29461
31	New Phase Research & Development	Knoxville	Tennessee	United States	37909
32	PMG Research Of Knoxville	Knoxville	Tennessee	United States	37938
33	Dallas Diabetes Endocrine Center	Dallas	Texas	United States	75230
34	Consano Clinical Research	Shavano Park	Texas	United States	78231
35	Chrysalis Clinical Research	Saint George	Utah	United States	84790
36	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Gdańsk		Poland	80-546
37	"For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician."	Gdynia		Poland	81-553
38	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Gdynia		Poland	81-553
39	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Katowice		Poland	40-772
40	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Szczecin		Poland	70-506
41	Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária LTDA	Łódź		Poland	90-242
42	Manati Center for Clinical Research	Manati		Puerto Rico	00674
43	Clinical Research Puerto Rico. Inc	San Juan		Puerto Rico	00909
44	GCM Medical Group PSC	San Juan		Puerto Rico	00909
45	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Košice		Slovakia	04012
46	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Malacky		Slovakia	90101
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Púchov		Slovakia	02001
48	"For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."	Trenčín		Slovakia	91101
49	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Trenčín		Slovakia	91101

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 - Nov 28, 2017
• Statistical Analysis Plan - Mar 26, 2018

More Information

Additional Information:

• A Study of tirzepatide in Participants With Type 2 Diabetes Mellitus

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03131687
• Other Study ID Numbers: 16335; I8F-MC-GPGB; 2016-004179-33
• First Posted: Apr 27, 2017
• Last Update Posted: Aug 20, 2019
• Last Verified: Apr 1, 2019

• 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
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Dulaglutide; Tirzepatide

Study Results

Participant Flow

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Period Title: Overall Study
STARTED	51	53	55	52	53	54
Received at Least One Dose of Study Drug	51	52	55	51	53	54
COMPLETED	45	44	52	48	45	49
NOT COMPLETED	6	9	3	4	8	5

Baseline Characteristics

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide	Total
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.	Total of all reporting groups
Overall Participants	51	52	55	51	53	54	316
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.6 (8.85)	57.4 (8.85)	57.9 (8.22)	56.5 (9.92)	56.0 (7.58)	58.7 (7.81)	57.2 (8.54)
Sex: Female, Male (Count of Participants)
Female	22 43.1%	23 44.2%	21 38.2%	21 41.2%	31 58.5%	30 55.6%	148 46.8%
Male	29 56.9%	29 55.8%	34 61.8%	30 58.8%	22 41.5%	24 44.4%	168 53.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	27 52.9%	25 48.1%	22 40%	26 51%	23 43.4%	19 35.2%	142 44.9%
Not Hispanic or Latino	19 37.3%	23 44.2%	23 41.8%	20 39.2%	27 50.9%	27 50%	139 44%
Unknown or Not Reported	5 9.8%	4 7.7%	10 18.2%	5 9.8%	3 5.7%	8 14.8%	35 11.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	5 9.8%	4 7.7%	1 1.8%	2 3.9%	2 3.8%	1 1.9%	15 4.7%
Asian	1 2%	0 0%	0 0%	1 2%	1 1.9%	2 3.7%	5 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 2%	1 1.9%	0 0%	2 0.6%
Black or African American	2 3.9%	5 9.6%	6 10.9%	7 13.7%	6 11.3%	4 7.4%	30 9.5%
White	41 80.4%	42 80.8%	46 83.6%	37 72.5%	43 81.1%	44 81.5%	253 80.1%
More than one race	2 3.9%	1 1.9%	2 3.6%	2 3.9%	0 0%	2 3.7%	9 2.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	1 2%	0 0%	1 1.9%	2 0.6%
Region of Enrollment (Count of Participants)
Puerto Rico	4 7.8%	4 7.7%	3 5.5%	3 5.9%	1 1.9%	1 1.9%	16 5.1%
United States	36 70.6%	37 71.2%	38 69.1%	37 72.5%	43 81.1%	43 79.6%	234 74.1%
Poland	6 11.8%	7 13.5%	4 7.3%	6 11.8%	6 11.3%	2 3.7%	31 9.8%
Slovakia	5 9.8%	4 7.7%	10 18.2%	5 9.8%	3 5.7%	8 14.8%	35 11.1%
Hemoglobin A1C (HbA1c) at Baseline (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	8.04 (0.861)	8.21 (0.905)	8.17 (0.961)	8.15 (1.072)	8.13 (1.061)	8.13 (0.954)	8.14 (0.966)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
Description	HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. The Least Squares Mean is Posterior mean.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a baseline and postbaseline excluding data after rescue drug initiation.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	44	45	52	47	44	49
Least Squares Mean (Standard Deviation) [Percentage of HbA1c]	-0.06 (0.14)	-1.06 (0.11)	-1.73 (0.08)	-1.89 (0.08)	-1.94 (0.09)	-1.21 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.17
	Estimation Comments	Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.67
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.17
	Estimation Comments	Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.83
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.17
	Estimation Comments	Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.89
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.17
	Estimation Comments	Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values.

2. Secondary Outcome

Title	Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
Description	HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. The Least Squares Mean is Posterior mean.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value excluding data after rescue drug initiation.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	48	45	52	48	48	51
Least Squares Mean (Standard Deviation) [Percentage of HbA1c]	-0.05 (0.13)	-0.94 (0.10)	-1.54 (0.07)	-1.68 (0.08)	-1.72 (0.08)	-1.08 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.15
	Estimation Comments	Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.49
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.15
	Estimation Comments	Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.62
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.15
	Estimation Comments	Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.67
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.15
	Estimation Comments	Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values.

3. Secondary Outcome

Title	Change From Baseline to Week 26 in HbA1c
Description	HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: Baseline + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug who had a baseline and postbaseline value excluding data after study drug discontinuation or rescue drug initiation.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	41	44	47	43	35	47
Least Squares Mean (Standard Error) [Percentage of HbA1c]	0.1 (0.16)	-0.7 (0.16)	-1.6 (0.15)	-2.0 (0.16)	-2.4 (0.17)	-1.1 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.2 to -1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -2.5 to -1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -2.9 to -2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Week 12 in HbA1c
Description	HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: Baseline + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

randomized participants who received at least one dose of study drug who had a baseline and postbaseline value excluding data after study drug discontinuation or rescue drug initiation.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	44	44	49	47	36	49
Least Squares Mean (Standard Error) [Percentage of HbA1c]	-0.1 (0.13)	-0.9 (0.13)	-1.7 (0.13)	-2.0 (0.13)	-2.1 (0.15)	-1.2 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.0 to -1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -2.3 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -2.4 to -1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with independent variables: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value excluding data after study drug discontinuation or rescue drug initiation.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	41	44	48	44	35	47
Least Squares Mean (Standard Error) [Kilograms (Kg)]	-0.4 (0.81)	-0.9 (0.80)	-4.8 (0.77)	-8.7 (0.80)	-11.3 (0.88)	-2.7 (0.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.655
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -2.7 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -6.6 to -2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.3
	Confidence Interval	(2-Sided) 95%; -10.5 to -6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-10.9
	Confidence Interval	(2-Sided) 95%; -13.3 to -8.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With 5% or Greater Body Weight Loss From Baseline
Description	Percentage of participants with 5% or greater body weight loss from baseline last observation carried forward (LOCF) analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	51	52	55	51	53	54
Number [percentage of participants]	0 0%	13.5 26%	47.3 86%	70.6 138.4%	62.3 117.5%	22.2 41.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

7. Secondary Outcome

Title	Percentage of Participants With 10% or Greater Body Weight Loss From Baseline
Description	Percentage of participants with 10% or greater body weight loss from baseline LOCF analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	51	52	55	51	53	54
Number [percentage of participants]	0 0%	5.8 11.2%	16.4 29.8%	39.2 76.9%	37.7 71.1%	9.3 17.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.193
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Regression, Logistic
	Comments

8. Secondary Outcome

Title	Percentage of Participants Reaching the HbA1c Target of ≤6.5%
Description	Percentage of participants with HbA1c ≤6.5% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug excluding data after study drug discontinuation or rescue drug initiation.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	51	52	55	50	53	54
Number [percentage of participants]	2.0 3.9%	15.4 29.6%	63.6 115.6%	82.0 160.8%	58.5 110.4%	38.9 72%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

9. Secondary Outcome

Title	Percentage of Participants Reaching the HbA1c Target of <7.0%
Description	Percentage of participants with HbA1c <7.0% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug excluding data after study drug discontinuation or rescue drug initiation.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	51	52	55	50	53	54
Number [percentage of participants]	11.8 23.1%	32.7 62.9%	69.1 125.6%	90.0 176.5%	77.4 146%	51.9 96.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

10. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose
Description	Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug who had a baseline and postbaseline value excluding data after study drug discontinuation or rescue drug initiation.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC. Dulaglutide placebo administered SC.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	40	44	48	44	35	46
Least Squares Mean (Standard Error) [milligrams per deciliter (mg/dL)]	15.5 (6.66)	-6.8 (6.43)	-40.7 (6.23)	-60.7 (6.36)	-57.5 (7.10)	-21.2 (6.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-22.4
	Confidence Interval	(2-Sided) 95%; -39.4 to -5.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-56.2
	Confidence Interval	(2-Sided) 95%; -72.9 to -39.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	-76.3
	Confidence Interval	(2-Sided) 95%; -93.3 to -59.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-73.0
	Confidence Interval	(2-Sided) 95%; -90.9 to -55.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Description	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag,Treatment, time, treatment*time.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	45	46	53	48	46	51
Least Squares Mean (Standard Error) [Millimoles Per Litre (mmol/L)]	0.0 (0.03)	-0.0 (0.03)	0.0 (0.03)	0.0 (0.03)	0.1 (0.03)	0.0 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.396
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.903
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.536
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.325
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.0 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Total Cholesterol
Description	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC. Tirzepatide placebo administered SC.
Measure Participants	45	46	53	48	46	51
Least Squares Mean (Standard Error) [Millimoles Per Litre (mmol/L)]	0.3 (0.13)	0.2 (0.13)	-0.1 (0.12)	-0.3 (0.12)	-0.3 (0.13)	-0.2 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.565
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -0.7 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in Triglycerides
Description	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	45	46	53	48	46	51
Least Squares Mean (Standard Error) [Millimoles Per Litre (mmol/L)]	0.3 (0.16)	-0.0 (0.16)	-0.5 (0.15)	-0.7 (0.15)	-0.8 (0.16)	-0.3 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.164
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.5 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)
Description	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered SC once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	42	45	52	48	45	50
Least Squares Mean (Standard Error) [Millimoles Per Litre (mmol/L)]	0.2 (0.12)	0.2 (0.11)	0.0 (0.11)	-0.0 (0.11)	-0.1 (0.12)	-0.1 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.919
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.194
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.067
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Change From Baseline in Waist Circumference
Description	LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered SC once weekly.	1 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.	1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Measure Participants	42	44	47	44	35	47
Least Squares Mean (Standard Error) [centimeters (cm)]	-1.3 (0.91)	-2.1 (0.89)	-5.1 (0.86)	-7.4 (0.88)	-10.2 (1.00)	-2.5 (0.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.539
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.1 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 5 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -6.1 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) 95%; -8.4 to -3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg Tirzepatide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.8
	Confidence Interval	(2-Sided) 95%; -11.3 to -6.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Number of Participants With Anti-Drug Antibodies
Description	Number of Participants With Anti-Drug Antibodies.
Time Frame	Baseline through Week 30

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide	1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC).	1 mg tirzepatide administered SC. Dulaglutide placebo administered SC.	5 mg tirzepatide administered SC. Dulaglutide placebo administered SC.	10 mg tirzepatide administered SC. Dulaglutide placebo administered SC.	15 mg tirzepatide administered SC. Dulaglutide placebo administered SC.	1.5 mg Dulaglutide administered SC. Tirzepatide placebo administered SC.
Measure Participants	51	52	55	51	53	54
Count of Participants [Participants]	0 0%	16 30.8%	19 34.5%	24 47.1%	26 49.1%	0 0%

17. Secondary Outcome

Title	Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide
Description	Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide
Time Frame	Predose: Week 1,8,12 and 26; Postdose: Week 1,2,4 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of Tirzepatide study drug excluding post rescue data.

Arm/Group Title	1 mg Tirzepatide	5 mg Tirzepatide	10 mg Tirzepatide	15 mg Tirzepatide
Arm/Group Description	1 mg tirzepatide administered SC. Dulaglutide placebo administered SC.	5 mg tirzepatide administered SC. Dulaglutide placebo administered SC.	10 mg tirzepatide administered SC. Dulaglutide placebo administered SC.	15 mg tirzepatide administered SC. Dulaglutide placebo administered SC.
Measure Participants	52	55	51	53
Geometric Mean (Geometric Coefficient of Variation) [Nanograms Per Millilitre (ng/mL)]	78.6 (29)	394 (29)	787 (29)	1180 (29)

Adverse Events

Time Frame	Up To 34 Weeks
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	Placebo		1 mg Tirzepatide		5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide + Placebo		1.5 mg Dulaglutide
Arm/Group Description	Tirzepatide placebo and dulaglutide placebo administered (SC) once weekly.		1 mg tirzepatide and placebo given SC once weekly.		5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.		10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.		15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.		1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
All Cause Mortality
	Placebo		1 mg Tirzepatide		5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide + Placebo		1.5 mg Dulaglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		1/52 (1.9%)		0/55 (0%)		0/51 (0%)		0/53 (0%)		0/54 (0%)
Serious Adverse Events
	Placebo		1 mg Tirzepatide		5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide + Placebo		1.5 mg Dulaglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/51 (3.9%)		2/52 (3.8%)		1/55 (1.8%)		3/51 (5.9%)		2/53 (3.8%)		3/54 (5.6%)
Cardiac disorders
Coronary artery disease	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	1/54 (1.9%)	1
Coronary artery occlusion	0/51 (0%)	0	1/52 (1.9%)	1	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Torsade de pointes	0/51 (0%)	0	1/52 (1.9%)	1	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Ventricular fibrillation	0/51 (0%)	0	1/52 (1.9%)	1	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Gastrointestinal disorders
Enteritis	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	1/53 (1.9%)	1	0/54 (0%)	0
Mesenteric vein thrombosis	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	1/51 (2%)	1	0/53 (0%)	0	0/54 (0%)	0
Pancreatitis acute	0/51 (0%)	0	0/52 (0%)	0	1/55 (1.8%)	2	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	1/54 (1.9%)	1
Cholecystitis acute	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	1/51 (2%)	1	0/53 (0%)	0	0/54 (0%)	0
Infections and infestations
Perirectal abscess	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	1/53 (1.9%)	1	0/54 (0%)	0
Pneumonia	2/51 (3.9%)	2	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Urosepsis	0/51 (0%)	0	1/52 (1.9%)	1	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Metabolism and nutrition disorders
Lactic acidosis	0/51 (0%)	0	1/52 (1.9%)	1	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	1/54 (1.9%)	1
Pathological fracture	1/51 (2%)	1	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma stage iv	1/51 (2%)	1	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	0/54 (0%)	0
Nervous system disorders
Cluster headache	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	0/53 (0%)	0	1/54 (1.9%)	1
Transient ischaemic attack	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	1/53 (1.9%)	1	0/54 (0%)	0
Vertebrobasilar insufficiency	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	1/53 (1.9%)	1	0/54 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	1/51 (2%)	1	0/53 (0%)	0	0/54 (0%)	0
Vascular disorders
Accelerated hypertension	0/51 (0%)	0	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	1/53 (1.9%)	1	0/54 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		1 mg Tirzepatide		5 mg Tirzepatide		10 mg Tirzepatide		15 mg Tirzepatide + Placebo		1.5 mg Dulaglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/51 (33.3%)		17/52 (32.7%)		29/55 (52.7%)		32/51 (62.7%)		39/53 (73.6%)		31/54 (57.4%)
Gastrointestinal disorders
Abdominal discomfort	2/51 (3.9%)	2	0/52 (0%)	0	1/55 (1.8%)	1	1/51 (2%)	2	4/53 (7.5%)	7	0/54 (0%)	0
Abdominal distension	1/51 (2%)	1	0/52 (0%)	0	2/55 (3.6%)	2	5/51 (9.8%)	5	4/53 (7.5%)	4	3/54 (5.6%)	3
Abdominal pain upper	1/51 (2%)	1	0/52 (0%)	0	1/55 (1.8%)	1	0/51 (0%)	0	3/53 (5.7%)	3	1/54 (1.9%)	1
Constipation	0/51 (0%)	0	1/52 (1.9%)	1	2/55 (3.6%)	2	6/51 (11.8%)	6	2/53 (3.8%)	2	3/54 (5.6%)	3
Diarrhoea	2/51 (3.9%)	2	7/52 (13.5%)	13	13/55 (23.6%)	17	12/51 (23.5%)	13	17/53 (32.1%)	23	9/54 (16.7%)	12
Dyspepsia	0/51 (0%)	0	0/52 (0%)	0	1/55 (1.8%)	2	6/51 (11.8%)	7	2/53 (3.8%)	2	2/54 (3.7%)	2
Nausea	3/51 (5.9%)	3	2/52 (3.8%)	2	11/55 (20%)	17	11/51 (21.6%)	13	21/53 (39.6%)	29	16/54 (29.6%)	22
Vomiting	1/51 (2%)	1	2/52 (3.8%)	2	4/55 (7.3%)	8	8/51 (15.7%)	9	14/53 (26.4%)	20	5/54 (9.3%)	6
Infections and infestations
Bronchitis	3/51 (5.9%)	4	1/52 (1.9%)	1	1/55 (1.8%)	1	3/51 (5.9%)	3	0/53 (0%)	0	2/54 (3.7%)	2
Influenza	1/51 (2%)	1	2/52 (3.8%)	2	2/55 (3.6%)	2	4/51 (7.8%)	4	1/53 (1.9%)	1	2/54 (3.7%)	2
Nasopharyngitis	2/51 (3.9%)	3	1/52 (1.9%)	2	3/55 (5.5%)	3	2/51 (3.9%)	5	3/53 (5.7%)	6	6/54 (11.1%)	6
Upper respiratory tract infection	3/51 (5.9%)	3	1/52 (1.9%)	1	3/55 (5.5%)	3	2/51 (3.9%)	3	1/53 (1.9%)	1	4/54 (7.4%)	5
Urinary tract infection	0/51 (0%)	0	2/52 (3.8%)	2	2/55 (3.6%)	2	1/51 (2%)	1	4/53 (7.5%)	4	0/54 (0%)	0
Injury, poisoning and procedural complications
Contusion	2/51 (3.9%)	2	0/52 (0%)	0	3/55 (5.5%)	3	0/51 (0%)	0	0/53 (0%)	0	1/54 (1.9%)	1
Investigations
Amylase increased	1/51 (2%)	1	0/52 (0%)	0	2/55 (3.6%)	3	4/51 (7.8%)	7	1/53 (1.9%)	3	0/54 (0%)	0
Lipase increased	1/51 (2%)	1	1/52 (1.9%)	1	3/55 (5.5%)	3	4/51 (7.8%)	7	2/53 (3.8%)	3	1/54 (1.9%)	1
Weight decreased	0/51 (0%)	0	2/52 (3.8%)	2	2/55 (3.6%)	2	5/51 (9.8%)	5	2/53 (3.8%)	2	0/54 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/51 (2%)	1	2/52 (3.8%)	2	11/55 (20%)	12	13/51 (25.5%)	14	10/53 (18.9%)	13	3/54 (5.6%)	3
Nervous system disorders
Dizziness	2/51 (3.9%)	3	4/52 (7.7%)	4	2/55 (3.6%)	2	2/51 (3.9%)	2	5/53 (9.4%)	5	1/54 (1.9%)	1
Headache	2/51 (3.9%)	2	2/52 (3.8%)	2	2/55 (3.6%)	2	1/51 (2%)	1	5/53 (9.4%)	5	1/54 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/51 (2%)	1	1/52 (1.9%)	1	1/55 (1.8%)	1	0/51 (0%)	0	3/53 (5.7%)	3	1/54 (1.9%)	1
Vascular disorders
Hypertension	1/51 (2%)	1	0/52 (0%)	0	0/55 (0%)	0	0/51 (0%)	0	1/53 (1.9%)	1	3/54 (5.6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.