A Study in Participants With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: LY2189265; Exenatide; Placebo; Metformin; Pioglitazone
Intervention MeSH terms: Metformin; Pioglitazone; Exenatide; Dulaglutide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 978.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if LY2189265 is effective and safe in reducing
      hemoglobin A1c (HbA1c), as compared to placebo (no medicine), or exenatide in participants
      with Type 2 Diabetes. The participants must also be taking metformin and pioglitazone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 Diabetes (T2D) not well controlled on 1, 2, or 3 oral antidiabetic medications

               1. Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal
                  to 11 if taking 1 oral antidiabetic medication

               2. HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral
                  antidiabetic medications

          -  Able to tolerate minimum dose of 1500 milligrams (mg) metformin a day and 30 mg
             pioglitazone per day.

          -  Willing to inject subcutaneous (SC) medication up to 2 times per day

          -  Stable weight for 3 months prior to screening

          -  Body mass index (BMI) between 23 and 45 kilograms per meter squared (kg/m^2)

          -  Females of child bearing potential must test negative for pregnancy at screening by
             serum pregnancy test and be willing to use a reliable method of birth control during
             the study and for 1 month following the last dose of study drug.

        Exclusion Criteria:

          -  Type 1 Diabetes

          -  HbA1c equal to or less than 6.5 before randomization or at randomization

          -  Chronic insulin use

          -  Taking drugs to promote weight loss by prescription or over the counter

          -  Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or
             inhaled

          -  History of fluid retention or edema

          -  History of Heart Failure New York Heart Classification II, III, or IV or acute
             myocardial infarction or stroke within 2 months of screening

          -  Gastrointestinal (GI; stomach) problems such as diabetic gastroparesis or bariatric
             surgery (stomach stapling) or chronically taking drugs that directly affect GI
             motility

          -  Hepatitis or liver disease or alanine transaminase (ALT) greater than 2.5 times the
             upper limit of normal

          -  Acute or chronic pancreatitis of any form

          -  Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5
             milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for
             females, or a creatine clearance of less than 60 milliliters per minute (mL/min)

          -  History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B)
             or medullary c-cell hyperplasia or thyroid cancer

          -  A serum calcitonin greater than or equal to 20 picograms per milliliter (pg/mL) at
             screening

          -  Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis

          -  History of or active malignancy except skin or in situ cervical or prostate cancer for
             within last 5 years

          -  Sickle cell, hemolytic anemia, or other hematological condition that may interfere
             with HbA1c testing

          -  Organ transplant except cornea

          -  Have enrolled in another clinical trial within the last 30 days

          -  Have previously signed an informed consent or participated in a LY2189265
             (dulaglutide) study

          -  Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months
             prior to screening