A Study of Dulaglutide (LY2189265) in Participants With T... | NCT02152371

ID	Type	Description	Link
H9X-MC-GBDI	Other Identifier	Eli Lilly and Company
2012-004229-25	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Dulaglutide + Insulin Glargine	Experimental	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.	Drug: Dulaglutide Drug: Insulin Glargine Drug: Metformin
Placebo + Insulin Glargine	Placebo Comparator	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.	Drug: Placebo Drug: Insulin Glargine Drug: Metformin

Name	Type	Description	Arm Group Labels	Other Names
Dulaglutide	Drug	Administered SQ	Dulaglutide + Insulin Glargine	LY2189265

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least-squares (LS) mean and standard error (SE) changes from baseline in HbA1c at 28 weeks were measured using mixed model regression and restricted maximum likelihood (REML) with treatment, pooled country, visit, and treatment-by -visit interaction as fixed effects, baseline as covariate, and participant as a random effect.	Baseline, 28 Weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)	FSG is a test to determine glucose levels after an overnight fast. LS means FSG change from baseline to primary endpoint at week 28 was calculated using a mixed effects model for repeated measures (MMRM) analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline FSG as covariate.	Baseline, 28 Weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have type 2 diabetes (based on the World Health Organization's [WHO] diagnostic criteria)
Have been treated with basal insulin glargine once daily with or without metformin for at least 3 months prior to screening
Doses of once daily insulin glargine and metformin (if taken) must be stable during the 3-month period prior to screening. Doses of metformin are considered stable if all prescribed doses during this period are in the range between the minimum required dose (≥1500 mg/day) and the maximum approved dose per the locally-approved label
Have an HbA1c value ≥7.0% and ≤10.5% as assessed by the central laboratory at screening
Require further insulin glargine dose increase at week 3 per the treat-to-target (TTT) algorithm based on the SMPG data collected during the prior week
Have stable weight (±5%) ≥3 months prior to screening
Have body mass index (BMI) ≤45 kilograms per square meter (kg/m^2) at screening
Are able and willing to administer once weekly randomized therapy
Are females of childbearing potential who must:
- Test negative for pregnancy at screening, based on a serum pregnancy test
- Agree to use a reliable method of birth control
- Not be breastfeeding

Exclusion Criteria:

Have been treated with ANY other antihyperglycemia regimen, other than basal insulin glargine once daily with or without metformin, within the 3 months prior to screening or between screening and week 3
Have a history of ≥1 episode of ketoacidosis or hyperosmolar state/coma
Have a history of hypoglycemia unawareness within the 6 months prior to screening
Have been treated with drugs that promote weight loss within the 3 months prior to screening or between screening and week 3
Are receiving chronic (>14 days) systemic glucocorticoid therapy or have received such therapy within the 4 weeks prior to screening or between screening and week 3
Have had any of the following cardiovascular conditions within the 2 months prior to screening: acute myocardial infarction (MI), New York Heart Association (NYHA) Class III or Class IV heart failure, or cerebrovascular accident (stroke)
Have a known clinically significant gastric emptying abnormality or have undergone gastric bypass surgery or restrictive bariatric surgery
Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or alanine aminotransferase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory
Have a history of chronic pancreatitis or acute idiopathic pancreatitis, or were diagnosed with any type of acute pancreatitis within the 3 months prior to screening
Have an estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73 square meter (mL/min/m^2), calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, as determined by the central laboratory; for participants on metformin, have renal disease or renal dysfunction (for example, a serum creatinine ≥1.5 mg/deciliter [dL] [male] or ≥1.4 mg/dL [female] or eGFR [CKD-EPI] <60 mL/min/1.73 m^2)
Have evidence of a significant, uncontrolled endocrine abnormality
Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia
Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, or carcinoma (including sporadic, familial, or part of MEN 2A or 2B syndrome)
Have serum calcitonin ≥20 picograms/mL, as determined by the central laboratory
Have evidence of a significant, active autoimmune abnormality
Have any other condition not listed in this section that is a contraindication for use of insulin glargine, or, for participants using metformin, have a condition that is a contraindication for the use of metformin and would require metformin discontinuation per label
Have a history of transplanted organ
Have a history of active or untreated malignancy, or are in remission from a clinically significant malignancy during the 5 years prior to screening
Have a history of any other condition which, in the opinion of the investigator, may preclude the participants from following and completing the protocol
Have any hematologic condition that may interfere with HbA1c measurement (eg, hemolytic anemias, sickle-cell disease)

Name	Affiliation	Role
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 Director

Facility	Status	City	State	ZIP	Country	Contacts
Valley Endocrine, Fresno		Fresno	California	93720	United States
Mills-Peninsula Diabetes Research Insitute

PubMed Identifier	Type	Citation	Retractions
29430801	Derived	Pantalone KM, Patel H, Yu M, Fernandez Lando L. Dulaglutide 1.5 mg as an add-on option for patients uncontrolled on insulin: Subgroup analysis by age, duration of diabetes and baseline glycated haemoglobin concentration. Diabetes Obes Metab. 2018 Jun;20(6):1461-1469. doi: 10.1111/dom.13252. Epub 2018 Mar 23.
29110972	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
FG001	Placebo + Insulin Glargine

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00060.2± 9.47 BG00160.6± 10.07 BG00260.4± 9.76

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00065 BG00162 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00026 BG00125 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Czech Republic

Title	Measurements
	BG00025 BG00127 BG002

Mean Insulin Glargine Dose

Mean

Standard Deviation

Units (U)

Title

Denominators

Categories

Title	Measurements
	BG00040.71± 23.12 BG00136.59± 21.46 BG002

Metformin Use at Baseline

Number

participants

Title

Denominators

Categories

Treated with Metformin

Title	Measurements
	BG000134 BG001131 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least-squares (LS) mean and standard error (SE) changes from baseline in HbA1c at 28 weeks were measured using mixed model regression and restricted maximum likelihood (REML) with treatment, pooled country, visit, and treatment-by -visit interaction as fixed effects, baseline as covariate, and participant as a random effect.

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

Posted

Least Squares Mean

Standard Error

percentage of change

Baseline, 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Units	Counts
Participants	OG000150 OG001150

Title

Denominators

Categories

Title	Measurements
	OG000-1.44± 0.09 OG001-0.67± 0.09

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Model for Repeated Measures (MMRM)		<.001		LS Means Diff	-0.77	Standard Error of the Mean	0.10	2-Sided	95	-0.97	-0.56					Superiority or Other (legacy)

Secondary

Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)

FSG is a test to determine glucose levels after an overnight fast. LS means FSG change from baseline to primary endpoint at week 28 was calculated using a mixed effects model for repeated measures (MMRM) analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline FSG as covariate.

All participants who received at least one dose of study drug and had evaluable baseline and post-baseline FSG data.

Posted

Least Squares Mean

Standard Error

milligram per deciliter (mg/dL)

Baseline, 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Secondary

Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)

The LS means of the 7-point SMPG change from baseline to primary endpoint at week 28 was measured using a MMRM analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline SMPG as covariate.

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

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Secondary

Change From Baseline to 28 Weeks in Body Weight

LS means of the body weight change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline body weight as covariate, via a MMRM analysis.

All participants who received at least one dose of study drug and had evaluable baseline and post-baseline body weight data.

Posted

Least Squares Mean

Standard Error

kilogram(kg)

Baseline, 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Units	Counts

Secondary

Change From Baseline to 28 Weeks in Daily Mean Insulin Glargine Dose

Least Square (LS) Means of the insulin dose change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline insulin dose as covariate, via a MMRM analysis.

All participants who one dose of study drug and had evaluable baseline and post-baseline insulin glargine data.

Posted

Least Squares Mean

Standard Error

units (u)

Baseline, 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Units

Secondary

Number of Participants With Investigator Reported and Adjudicated Cardiovascular Events

Cardiovascular (CV) adverse events (AEs) were adjudicated by an independent committee of physicians with cardiology expertise external to the sponsor. Deaths occurring during the study treatment period and nonfatal CV AEs were to be adjudicated. Nonfatal CV events that were to be adjudicated were myocardial infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary interventions (such as coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI); and cerebrovascular events, including cerebrovascular accident (CVA/stroke), and transient ischemic attack (TIA).

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

Posted

Number

participants

Baseline through 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Secondary

Percentage of Participants With Self-Reported Events of Hypoglycemia

Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The percentage of participants with self-reported hypoglycemic events is presented.

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

Posted

Number

percentage of participants

Baseline through 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Secondary

Percentage of Participants Discontinuing the Study Due to Severe, Persistent Hyperglycemia

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

Posted

Number

percentage of participants

Baseline through 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Units	Counts
Participants	OG000

Secondary

Number of Participants With Adjudicated Acute Pancreatitis Events

The number of cases of acute pancreatitis confirmed by adjudication. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

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

Posted

Number

participants

Baseline through 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Units	Counts
Participants

Secondary

Number of Participants With Thyroid Tumors/Neoplasms (Including C-Cell Hyperplasia)

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

Posted

Number

participants

Baseline through 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Units	Counts
Participants	OG000

Secondary

Number of Participants With Dulaglutide Anti-Drug Antibodies

Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 12 and 28. 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.

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

Posted

Number

participants

Baseline, Week 12 and Week 28

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Secondary

Percentage of Participants Achieving HbA1c Targets of <7.0% or ≤6.5%

Percentage of participants who achieved HbA1c levels of <7% or ≤6.5% were analyzed using a logistic regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.

All randomized participants who received at least 1 dose of study drug and had a baseline and post-baseline HbA1c data. Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values.

Posted

Number

percentage of participants

28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Secondary

Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 Kilograms [kg]) at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)

Percentage of participants who achieved a target HbA1c target of <7%, without weight gain and without documented symptomatic hypoglycemia at 28 weeks were analyzed using regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.

All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline HbA1c data.Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values.

Posted

Number

percentage of participants

28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Secondary

Percentage of Participants Achieving HbA1c Target of <7.0% at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)

Percentage of participants achieving target HbA1c of <7.0% at 28 weeks without documented symptomatic hypoglycemia are presented. Documented symptomatic hypoglycemia is defined as any time a participant experienced symptoms and or signs associated with hypoglycemia and had a plasma glucose of <=70 mg/dL.

All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline HbA1c data. Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values

Posted

Number

percentage of participants

28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Secondary

Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 kg)

All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline HbA1c data. Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values.

Posted

Number

percentage of participants

28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Units	Counts
Participants

Secondary

Rate of Hypoglycemic Events up to 28 Weeks

The rate of total hypoglycemic events any type per 30 days is presented. The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period*30 days.

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

Posted

Mean

Standard Deviation

rate of hypoglycemic events per 30 days

Baseline through 28 Weeks

ID	Title	Description
OG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
OG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally			9	150	51	150
EG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally			7	150	29	150

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina unstable	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0011 events1 affected150 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Bradycardia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected150 at risk EG0010 events0 affected150 at risk
Coronary artery disease	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Myocardial infarction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Non-cardiac chest pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected150 at risk
Granulomatous liver disease	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Viral infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected150 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected150 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected150 at risk
Hepatic cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected150 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Cerebral infarction	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected150 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected150 at risk EG0010 events0 affected150 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected150 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00019 events17 affected150 at risk EG0016 events6 affected150 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0009 events9 affected150 at risk EG0010 events0 affected150 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00023 events18 affected150 at risk EG0013 events2 affected150 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00011 events9 affected150 at risk EG0010 events0 affected150 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0007 events6 affected150 at risk EG00119 events14 affected150 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00018 events11 affected150 at risk EG00110 events10 affected150 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG00011 events10 affected150 at risk EG0010 events0 affected150 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

ID	Title	Description
BG000	Dulaglutide + Insulin Glargine	1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
BG001	Placebo + Insulin Glargine	Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
BG002	Total	Total of all reporting groups

ID	Term
C555680	dulaglutide
D000069036	Insulin Glargine
D008687	Metformin