A Study of Dulaglutide (LY2189265) in Participants With Type II Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dulaglutide; Placebo; Insulin Glargine; Metformin
Intervention description: Administered SQ; Administered SQ; Administered SQ; Administered orally
Intervention MeSH terms: Metformin; Insulin Glargine; Dulaglutide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 300.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to evaluate the use of the study drug known as dulaglutide
      in participants with type II diabetes who are taking once-daily insulin glargine. The study
      will last about 31 weeks for each participant.
    

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)