AWARD-PEDS: A Study of Dulaglutide (LY2189265) in Children and Adolescents With Type 2 Diabetes

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02963766
• Collaborator: (none)
• Enrollment: 154
• Locations: 61
• Arms: 3
• Actual Duration (Months): 60.5
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of the study drug dulaglutide compared to placebo in pediatric participants with type 2 diabetes. The study duration is approximately 60 weeks.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind Study With an Open-Label Extension Comparing the Effect of Once-Weekly Dulaglutide With Placebo in Pediatric Patients With Type 2 Diabetes Mellitus (AWARD-PEDS: Assessment of Weekly AdministRation of LY2189265 in Diabetes-PEDiatric Study)
• Actual Study Start Date: Dec 29, 2016
• Actual Primary Completion Date: Jun 12, 2021
• Actual Study Completion Date: Jan 12, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo/0.75 milligram (mg) Dulaglutide Participants received placebo administered subcutaneously (SC) for 26 weeks during the double-blind period and open-label 0.75 mg/week dulaglutide for 26 weeks during the Open Label Extension (OLE).	Drug: Dulaglutide; Administered SC; Other Names: LY2189265 ; Drug: Placebo; Administered SC
Experimental: 0.75 mg Dulaglutide Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week for 26 weeks during the OLE.	Drug: Dulaglutide; Administered SC; Other Names: LY2189265
Experimental: 1.5 mg Dulaglutide Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 1.5 mg/week for 26 weeks during the OLE.	Drug: Dulaglutide; Administered SC; Other Names: LY2189265

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses) at Week 26 [Baseline, Week 26]

   HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean in HbA1c was calculated using a restricted maximum likelihood (REML) based mixed-effects model for repeated measures (MMRM) and adjusted by, baseline + insulin Use + metformin Use + treatment + time + treatment*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline).

Secondary Outcome Measures

1. Change From Baseline in HbA1c (Individual Doses) at Week 26 [Baseline, Week 26]

   HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean in HbA1c was calculated using a REML based MMRM and adjusted by, baseline + insulin use + metformin use + treatment + time + treatment*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline).

2. Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 [Baseline, Week 26]

   Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis and adjusted by baseline, strata, treatment, time, treatment*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group [ less than (<) 8%, greater than or equal to (>=) 8%).

3. Percentage of Participants With HbA1c ≤7.0% [Week 26]

   The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.

4. Change From Baseline in Body Mass Index (BMI) at Week 26 [Baseline, Week 26]

   BMI is an estimate of body fat based on body weight divided by height squared. LS mean were calculated using a MMRM analysis and adjusted by baseline, strata, treatment, time, treatment*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group (< 8%, >= 8%).

5. Percentage of Participants With Self-Reported Events of Hypoglycemia [Week 26]

   Summary and analysis of Incidence of all hypoglycemia with Plasma Glucose <54mg/dL.

6. Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia [Week 26]

   Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia was summarized.

7. Number of Participants With Adjudicated Pancreatitis [Week 26]

   The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

8. Change From Baseline in Pancreatic Enzymes at Week 26 [Baseline, Week 26]

   Serum Amylase (total and pancreas-derived) and lipase concentrations were measured.

9. Number of Participants With Thyroid Treatment-Emergent Adverse Events [Week 26]

   Number of Participants with Thyroid Treatment-Emergent Adverse Events were summarized.

10. Change From Baseline in Serum Calcitonin at Week 26 [Baseline, Week 26]

    Change from Baseline in Serum Calcitonin was evaluated.

11. Percentage of Participants With Allergic, Hypersensitivity Reactions [Week 26]

    The percentage of Participants with Allergic and hypersensitivity reactions that were considered possibly related to study drug by the investigator are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

12. Percentage of Participants With Injection Site Reactions [Week 26]

    The percentage of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

13. Number of Participants With Anti-Dulaglutide Antibodies [Baseline through Week 56]

    Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 26 and 56. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.

14. Pharmacokinetics (PK): Maximum Concentration of Dulaglutide at Steady-state (Cmax,ss) [Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit]

    PK: Maximum Concentration of Dulaglutide at steady-state (Cmax,ss) was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9.

15. PK: Area Under the Concentration Time Curve Over a 1-week Interval of Dulaglutide at Steady-State [AUC(0-168)ss] [Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit]

    PK: Area Under the Concentration Time Curve over a 1-week interval of Dulaglutide at Steady-State [AUC(0-168)ss] was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have type 2 diabetes, treated with diet and exercise, with or without metformin and/or basal insulin. Metformin and/or basal insulin dose must be stable for at least 8 weeks prior to study screening.

• Have HbA1c >6.5% to ≤11% at screening visit. If newly diagnosed and not on medicine for diabetes, HbA1c must be between >6.5 % to ≤9%.

• Have a BMI (body mass index) >85 percentile for age, gender and body weight ≥50 kilograms (110 pounds).

Exclusion Criteria:

• Known type 1 diabetes, or positive GAD65 or IA2 antibodies, or history of diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome.

• A history of, or at risk for pancreatitis.

• Self or family history of Multiple Endocrine Neoplasia (MEN) type 2A or B, thyroid C-cell hyperplasia or medullary thyroid cancer, or a blood calcitonin result ≥20 picograms per milliliter (pg/ml) at screening.

• A systolic blood pressure of ≥160 millimeters of mercury (mmHg) or diastolic ≥100 mmHg.

• Active or treated cancer.

• A blood disorder where an accurate HbA1c may not be obtainable.

• A female of childbearing age, sexually active and not on birth control.

• Pregnant or plan to be pregnant during the study, or breastfeeding.

• Taking any diabetic medication other than metformin or basal insulin and have not stopped it 3 months prior to the screening visit (6 weeks for bolus or mealtime insulin).

• Have taken oral steroids within the last 60 days or more than 20 days use within the past year or 1000 micrograms fluticasone propionate per day.

• Using prescription weight loss medications in the last 30 days, or plan to use.

• Taking psychiatric medications for depression or illness or attention deficit hyperactivity disorder (ADHD) if, the doses has changed within the last 3 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States	35233
2	University of Arizona	Tucson	Arizona	United States	85724
3	Advanced Research Center	Anaheim	California	United States	92805
4	Division of Endocrinology, Diabetes, and Metabolism	Los Angeles	California	United States	90027
5	Childrens Hospital of Orange County	Orange	California	United States	92868
6	Center of Excellence in Diabetes & Endocrinology	Sacramento	California	United States	95821
7	Rady Childrens Hospital - San Diego	San Diego	California	United States	92123
8	JC Cabaccan	San Jose	California	United States	95148
9	Touro University	Vallejo	California	United States	94592
10	Children's National Medical Center	Washington	District of Columbia	United States	20010
11	Florida Center for Endocrinology & Metabolism	Orlando	Florida	United States	32803
12	St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
13	University of Illinois at Chicago	Chicago	Illinois	United States	60612
14	Indiana University Health Hospital	Indianapolis	Indiana	United States	46202
15	Pennington Biomedical Research Center	Baton Rouge	Louisiana	United States	70808-4124
16	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
17	ECU Pediatric Specialty Care	Greenville	North Carolina	United States	27834
18	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio	United States	45229
19	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
20	Childrens Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
21	Seattle Children's Hospital Research Foundation	Seattle	Washington	United States	98105
22	Multicare Health System	Tacoma	Washington	United States	98405
23	CAMC Institute	Charleston	West Virginia	United States	25302
24	Centro de Pesquisas em Diabetes	Porto Alegre	Rio Grande Do Sul	Brazil	90430-001
25	Instituto da Criança com Diabetes	Porto Alegre	Rio Grande Do Sul	Brazil	91350-200
26	Instituto Estadual de Diabetes e Endocrinologia	Rio de Janeiro	RJ	Brazil	20211-340
27	Hospital PUC-CAMPINAS	Campinas	Sao Paulo	Brazil	13034-685
28	CPCLIN	São Paulo	SP	Brazil	01228-200
29	Hospital da Clinicas da Faculdade de Medicina da USP	São Paulo	SP	Brazil	05403-000
30	Hospital das Clinicas da FMRP	Ribeirão Preto	São Paulo	Brazil	14051-140
31	UNIFESP - Escola Paulista de Medicina	São Paulo		Brazil	04022-001
32	Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre	Le Kremlin Bicetre		France	94275
33	Hopital Robert Debre	Paris		France	75019
34	Praxis Dr. med. Landers	Mayen	Rheinland-Pfalz	Germany	56727
35	Zentrum für klinische Studien	Sankt Ingbert	Saarland	Germany	66386
36	RED-Institut GmbH	Oldenburg in Holstein	Schleswig Holstein	Germany	23758
37	Heim Pal Gyermekkorhaz	Budapest		Hungary	1089
38	Sir Ganga Ram Hospital	New Delhi	Delhi	India	110060
39	Dr Jivraj Mehta Smarak Health Foundation Bakeri Medical Research Centre	Ahmedabad	Gujarat	India	380007
40	Manipal Hospital	Bangalore	Karmnataka	India	560017
41	M S Ramaiah Medical College Hospital	Bangalore	Karnataka	India	560054
42	Deenanath Mangeshkar Hospital & Research Centre	Pune	Maharashtra	India	411004
43	Post Graduate Institute of Medical Education & Research	Chandigarh	Punjab	India	160012
44	Banaras Hindu University - BHU	Varanasi	Uttar Pradesh	India	221005
45	Park Clinic	Kolkata	West Bengal	India	700017
46	Apollo Gleneagles Hospitals Kolkata	Kolkata	West Bengal	India	700054
47	Health Pharma Professional Research, S.A. de C.V.	Mexico City	Federal District	Mexico	03810
48	Centro de Inv. Medica de Occidente, SC	Zapopan	Jalisco	Mexico	45116
49	Centro Medico San Francisco	Monterrey	Nuevo Leon	Mexico	64710
50	Cli-nica Hospital Cemain	Tampico	Tamaulipas	Mexico	89249
51	Hospital Angeles Puebla	Puebla		Mexico	72190
52	Arke Estudios Clinicos S.A. de C.V.	Veracruz		Mexico	91910
53	Centro de Diabetes y Endocrinologia Pediatrica de PR	Bayamon		Puerto Rico	00959
54	King Saud University Hospital	Riyadh		Saudi Arabia	11472
55	King Salman bin Abdulaziz Hospital - Diabetic Center	Riyadh		Saudi Arabia	12769
56	Ankara University Medicine Hospital	Ankara	Mamak	Turkey	06100
57	Sami Ulus Education & Research Hospital	Ankara		Turkey	06080
58	Duzce University Medical Faculty	Duzce		Turkey	81620
59	Ondokuz Mayis University Medical Faculty	Samsun		Turkey	55139
60	Alder Hey Children's Hospital	Liverpool	Lancashire	United Kingdom	L14 5AB
61	St James's University Hospital	Leeds	West Yorkshire	United Kingdom	LS9 7TF

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 - Oct 15, 2020
• Statistical Analysis Plan - Feb 18, 2021

More Information

Additional Information:

• A Study of Dulaglutide (LY2189265) in Children and Adolescents With Type 2 Diabetes (AWARD-PEDS)

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02963766
• Other Study ID Numbers: 14171; H9X-MC-GBGC; 2016-000361-22
• First Posted: Nov 15, 2016
• Last Update Posted: Jul 1, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: Pediatrics
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Dulaglutide

Study Results

Participant Flow

Arm/Group Title	Placebo/0.75 Milligram (mg) Dulaglutide	0.75 mg Dulaglutide	1.5 mg Dulaglutide
Arm/Group Description	Participants received placebo administered subcutaneously (SC) for 26 weeks during the double-blind period and open-label 0.75 mg/week dulaglutide for 26 weeks during the open Label Extension (OLE).	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week for 26 weeks during the OLE.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 1.5 mg/week for 26 weeks during the OLE.
Period Title: Double-Blind Period
STARTED	51	51	52
Received at Least 1 Dose of Study Drug	51	51	52
COMPLETED	47	49	50
NOT COMPLETED	4	2	2
Period Title: Double-Blind Period
STARTED	47	49	50
COMPLETED	45	46	48
NOT COMPLETED	2	3	2

Baseline Characteristics

Arm/Group Title	Placebo/0.75 mg Dulaglutide	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Total
Arm/Group Description	Participants received placebo administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week dulaglutide for 26 weeks during the OLE.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week for 26 weeks during the OLE.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 1.5 mg/week for 26 weeks during the OLE.	Total of all reporting groups
Overall Participants	51	51	52	154
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.20 (2.08)	14.70 (2.21)	14.70 (1.81)	14.50 (2.04)
Sex: Female, Male (Count of Participants)
Female	41 80.4%	35 68.6%	34 65.4%	110 71.4%
Male	10 19.6%	16 31.4%	18 34.6%	44 28.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	26 51%	31 60.8%	28 53.8%	85 55.2%
Not Hispanic or Latino	25 49%	18 35.3%	22 42.3%	65 42.2%
Unknown or Not Reported	0 0%	2 3.9%	2 3.8%	4 2.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 11.8%	6 11.8%	4 7.7%	16 10.4%
Asian	11 21.6%	4 7.8%	4 7.7%	19 12.3%
Native Hawaiian or Other Pacific Islander	1 2%	0 0%	0 0%	1 0.6%
Black or African American	5 9.8%	9 17.6%	9 17.3%	23 14.9%
White	25 49%	29 56.9%	30 57.7%	84 54.5%
More than one race	3 5.9%	1 2%	3 5.8%	7 4.5%
Unknown or Not Reported	0 0%	2 3.9%	2 3.8%	4 2.6%
Region of Enrollment (Count of Participants)
Brazil	4 7.8%	7 13.7%	5 9.6%	16 10.4%
France	0 0%	2 3.9%	2 3.8%	4 2.6%
Germany	2 3.9%	1 2%	0 0%	3 1.9%
India	3 5.9%	4 7.8%	4 7.7%	11 7.1%
Mexico	14 27.5%	12 23.5%	10 19.2%	36 23.4%
Puerto Rico	0 0%	1 2%	1 1.9%	2 1.3%
Saudi Arabia	2 3.9%	0 0%	1 1.9%	3 1.9%
Turkey	1 2%	1 2%	1 1.9%	3 1.9%
United Kingdom	3 5.9%	2 3.9%	0 0%	5 3.2%
United States	22 43.1%	21 41.2%	28 53.8%	71 46.1%
Percentage of Hemoglobin A1c (HbA1c) at Baseline (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	8.14 (1.12)	7.92 (1.27)	8.16 (1.39)	8.08 (1.26)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses) at Week 26
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean in HbA1c was calculated using a restricted maximum likelihood (REML) based mixed-effects model for repeated measures (MMRM) and adjusted by, baseline + insulin Use + metformin Use + treatment + time + treatment*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline).
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 evaluable baseline and post-baseline HbA1c.

Arm/Group Title	Placebo	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	45	100
Least Squares Mean (Standard Error) [percentage of HbA1C]	0.5 (0.24)	-0.7 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -1.8 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in HbA1c (Individual Doses) at Week 26
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean in HbA1c was calculated using a REML based MMRM and adjusted by, baseline + insulin use + metformin use + treatment + time + treatment*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline).
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 evaluable baseline and post-baseline HbA1c.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	45	50	50
Least Squares Mean (Standard Error) [percentage of HbA1c]	0.5 (0.24)	-0.5 (0.22)	-1.0 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.7 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1.5 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (FBG) at Week 26
Description	Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis and adjusted by baseline, strata, treatment, time, treatment*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group [ less than (<) 8%, greater than or equal to (>=) 8%).
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 evaluable fasting blood glucose data. Only pre-rescue measurements were used.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	43	49	50	99
Least Squares Mean (Standard Error) [millimoles per liter (mmol/L)]	0.96 (0.45)	-0.47 (0.41)	-1.54 (0.41)	-1.03 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-1.44
	Confidence Interval	(2-Sided) 95%; -2.65 to -0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1.5 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-2.51
	Confidence Interval	(2-Sided) 95%; -3.72 to -1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-1.97
	Confidence Interval	(2-Sided) 95%; -3.03 to -0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With HbA1c ≤7.0%
Description	The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable baseline and post-baseline HbA1c.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	45	50	50	100
Number [percentage of participants]	18.42 36.1%	60.00 117.6%	53.19 102.3%	56.52 36.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.038
	Confidence Interval	(2-Sided) 95%; 3.491 to 34.902
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1.5 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.666
	Confidence Interval	(2-Sided) 95%; 3.653 to 37.253
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.348
	Confidence Interval	(2-Sided) 95%; 4.163 to 30.932
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Body Mass Index (BMI) at Week 26
Description	BMI is an estimate of body fat based on body weight divided by height squared. LS mean were calculated using a MMRM analysis and adjusted by baseline, strata, treatment, time, treatment*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group (< 8%, >= 8%).
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 evaluable BMI data.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	50	51	52	103
Least Squares Mean (Standard Error) [kilograms/square meter (kg/m^2)]	-0.0 (0.21)	-0.2 (0.20)	-0.1 (0.19)	-0.1 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.689
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 1.5 mg Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.924
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Dulaglutide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.776
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Self-Reported Events of Hypoglycemia
Description	Summary and analysis of Incidence of all hypoglycemia with Plasma Glucose <54mg/dL.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	51	51	52
Number [percentage of participants]	1.96 3.8%	3.92 7.7%	3.85 7.4%

7. Secondary Outcome

Title	Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia
Description	Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia was summarized.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	51	51	52	103
Number [percentage of participants]	17.6 34.5%	3.9 7.6%	1.9 3.7%	2.9 1.9%

8. Secondary Outcome

Title	Number of Participants With Adjudicated Pancreatitis
Description	The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	51	51	52	103
Number [participants]	0 0%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Change From Baseline in Pancreatic Enzymes at Week 26
Description	Serum Amylase (total and pancreas-derived) and lipase concentrations were measured.
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 evaluable pancreatic enzymes data.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	47	51	52	103
Serum Amylase	0.09 (17.36)	4.80 (9.39)	6.50 (8.91)	5.64 (9.15)
Serum Amylase, Pancreatic	0.60 (9.94)	1.77 (4.72)	2.90 (6.10)	2.32 (5.45)
Serum Lipase	2.23 (31.99)	4.37 (8.28)	3.88 (6.63)	4.12 (7.47)

10. Secondary Outcome

Title	Number of Participants With Thyroid Treatment-Emergent Adverse Events
Description	Number of Participants with Thyroid Treatment-Emergent Adverse Events were summarized.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	51	51	52	103
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

11. Secondary Outcome

Title	Change From Baseline in Serum Calcitonin at Week 26
Description	Change from Baseline in Serum Calcitonin was evaluated.
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 evaluable serum calcitonin data.

Arm/Group Title	Placebo	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	47	48	48	96
Mean (Standard Deviation) [nanograms per liter (ng/L)]	0.38 (1.70)	0.28 (0.72)	0.10 (0.50)	0.19 (0.62)

12. Secondary Outcome

Title	Percentage of Participants With Allergic, Hypersensitivity Reactions
Description	The percentage of Participants with Allergic and hypersensitivity reactions that were considered possibly related to study drug by the investigator are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
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	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	51	51	52	103
Number [percentage of participants]	2.0 3.9%	3.9 7.6%	1.9 3.7%	2.9 1.9%

13. Secondary Outcome

Title	Percentage of Participants With Injection Site Reactions
Description	The percentage of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
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	0.75 mg Dulaglutide	1.5 mg Dulaglutide	Pooled Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.	Participants received pooled: 0.75 mg/week dulaglutide and 1.5 mg/week dulaglutide administered SC for 26 weeks.
Measure Participants	51	51	52	103
Number [percentage of participants]	9.8 19.2%	9.8 19.2%	7.7 14.8%	8.7 5.6%

14. Secondary Outcome

Title	Number of Participants With Anti-Dulaglutide Antibodies
Description	Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 26 and 56. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.
Time Frame	Baseline through Week 56

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least one post-baseline Dulaglutide ADA test result.

Arm/Group Title	Placebo/0.75 mg Dulaglutide	0.75 mg Dulaglutide	1.5 mg Dulaglutide
Arm/Group Description	Participants received placebo administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week dulaglutide for 26 weeks during the open OLE.	Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week for 26 weeks during the OLE.	Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 1.5 mg/week for 26 weeks during the OLE.
Measure Participants	46	51	52
Number [participants]	3 5.9%	3 5.9%	3 5.8%

15. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration of Dulaglutide at Steady-state (Cmax,ss)
Description	PK: Maximum Concentration of Dulaglutide at steady-state (Cmax,ss) was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9.
Time Frame	Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	0.75 mg Dulaglutide	1.5 mg Dulaglutide
Arm/Group Description	Participants received 0.75 mg/week dulaglutide administered SC for 56 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 56 weeks.
Measure Participants	51	52
Mean (95% Confidence Interval) [nanograms per milliliter (ng/mL)]	31	62

16. Secondary Outcome

Title	PK: Area Under the Concentration Time Curve Over a 1-week Interval of Dulaglutide at Steady-State [AUC(0-168)ss]
Description	PK: Area Under the Concentration Time Curve over a 1-week interval of Dulaglutide at Steady-State [AUC(0-168)ss] was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9.
Time Frame	Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	0.75 mg Dulaglutide	1.5 mg Dulaglutide
Arm/Group Description	Participants received 0.75 mg/week dulaglutide administered SC for 56 weeks.	Participants received 1.5 mg/week dulaglutide administered SC for 56 weeks.
Measure Participants	51	52
Mean (95% Confidence Interval) [nanogram*hour per milliliter (ng*h/ mL)]	4170	8350

Adverse Events

Time Frame	Up To 56 Weeks
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug. The gender specific events only occurring in male or female participants were adjusted accordingly.
Arm/Group Title	Placebo: Double-Blind Period		0.75 mg Dulaglutide: Double-Blind Period		1.5 mg Dulaglutide: Double-Blind Period		Placebo/0.75 mg Dulaglutide: Open Label Extension (OLE)		0.75 mg Dulaglutide: OLE		1.5 mg Dulaglutide: OLE
Arm/Group Description	Participants received placebo administered SC for 26 weeks.		Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks.		Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks.		Participants who had received placebo during the double-blind period were given 0.75 mg/week dulaglutide administered SC for additional 26 weeks after the double-blind period.		Participants received 0.75 mg/week dulaglutide administered SC for additional 26 weeks after the double-blind period.		Participants received 1.5 mg/week dulaglutide administered SC for additional 26 weeks after the double-blind period.
All Cause Mortality
	Placebo: Double-Blind Period		0.75 mg Dulaglutide: Double-Blind Period		1.5 mg Dulaglutide: Double-Blind Period		Placebo/0.75 mg Dulaglutide: Open Label Extension (OLE)		0.75 mg Dulaglutide: OLE		1.5 mg Dulaglutide: OLE
	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%)		0/51 (0%)		0/52 (0%)		0/47 (0%)		0/49 (0%)		0/50 (0%)
Serious Adverse Events
	Placebo: Double-Blind Period		0.75 mg Dulaglutide: Double-Blind Period		1.5 mg Dulaglutide: Double-Blind Period		Placebo/0.75 mg Dulaglutide: Open Label Extension (OLE)		0.75 mg Dulaglutide: OLE		1.5 mg Dulaglutide: OLE
	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	3/51 (5.9%)		1/51 (2%)		1/52 (1.9%)		0/47 (0%)		1/49 (2%)		2/50 (4%)
Cardiac disorders
Right ventricular failure	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Hepatobiliary disorders
Nonalcoholic fatty liver disease	0/51 (0%)	0	1/51 (2%)	1	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Infections and infestations
Genital herpes	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Pilonidal cyst	0/51 (0%)	0	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Pyelonephritis	0/51 (0%)	0	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Injury, poisoning and procedural complications
Carbon monoxide poisoning	0/51 (0%)	0	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Stress fracture	0/51 (0%)	0	0/51 (0%)	0	1/52 (1.9%)	1	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Psychiatric disorders
Suicide attempt	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Respiratory failure	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo: Double-Blind Period		0.75 mg Dulaglutide: Double-Blind Period		1.5 mg Dulaglutide: Double-Blind Period		Placebo/0.75 mg Dulaglutide: Open Label Extension (OLE)		0.75 mg Dulaglutide: OLE		1.5 mg Dulaglutide: OLE
	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	26/51 (51%)		25/51 (49%)		28/52 (53.8%)		18/47 (38.3%)		16/49 (32.7%)		20/50 (40%)
Gastrointestinal disorders
Abdominal pain	3/51 (5.9%)	3	4/51 (7.8%)	4	1/52 (1.9%)	4	0/47 (0%)	0	3/49 (6.1%)	5	3/50 (6%)	3
Abdominal pain upper	4/51 (7.8%)	8	3/51 (5.9%)	3	5/52 (9.6%)	6	2/47 (4.3%)	2	0/49 (0%)	0	5/50 (10%)	21
Diarrhoea	7/51 (13.7%)	9	8/51 (15.7%)	13	11/52 (21.2%)	19	0/47 (0%)	0	1/49 (2%)	1	6/50 (12%)	21
Nausea	4/51 (7.8%)	4	7/51 (13.7%)	16	8/52 (15.4%)	13	1/47 (2.1%)	2	3/49 (6.1%)	10	6/50 (12%)	12
Vomiting	2/51 (3.9%)	2	9/51 (17.6%)	10	7/52 (13.5%)	14	4/47 (8.5%)	6	4/49 (8.2%)	4	5/50 (10%)	8
General disorders
Pyrexia	2/51 (3.9%)	2	2/51 (3.9%)	3	2/52 (3.8%)	2	2/47 (4.3%)	3	3/49 (6.1%)	3	1/50 (2%)	1
Infections and infestations
Gastroenteritis	2/51 (3.9%)	3	1/51 (2%)	1	3/52 (5.8%)	3	4/47 (8.5%)	5	0/49 (0%)	0	3/50 (6%)	4
Nasopharyngitis	3/51 (5.9%)	4	5/51 (9.8%)	6	2/52 (3.8%)	2	4/47 (8.5%)	4	1/49 (2%)	1	3/50 (6%)	3
Upper respiratory tract infection	4/51 (7.8%)	6	2/51 (3.9%)	3	6/52 (11.5%)	7	3/47 (6.4%)	4	0/49 (0%)	0	1/50 (2%)	1
Urinary tract infection	3/51 (5.9%)	3	2/51 (3.9%)	3	0/52 (0%)	0	2/47 (4.3%)	2	1/49 (2%)	1	0/50 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	0/51 (0%)	0	3/51 (5.9%)	3	2/52 (3.8%)	2	0/47 (0%)	0	0/49 (0%)	0	0/50 (0%)	0
Nervous system disorders
Dizziness	1/51 (2%)	1	4/51 (7.8%)	4	2/52 (3.8%)	2	1/47 (2.1%)	1	1/49 (2%)	1	1/50 (2%)	1
Headache	5/51 (9.8%)	8	7/51 (13.7%)	7	8/52 (15.4%)	21	2/47 (4.3%)	2	5/49 (10.2%)	6	5/50 (10%)	6
Reproductive system and breast disorders
Dysmenorrhoea	1/41 (2.4%)	1	1/35 (2.9%)	1	2/34 (5.9%)	4	0/38 (0%)	0	0/34 (0%)	0	3/34 (8.8%)	3
Heavy menstrual bleeding	0/41 (0%)	0	0/35 (0%)	0	2/34 (5.9%)	2	0/38 (0%)	0	0/34 (0%)	0	0/34 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	3/47 (6.4%)	3	0/49 (0%)	0	0/50 (0%)	0

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.