A Study in Participants With Type 2 Diabetes Mellitus

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.

During the study, if a participant developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, the participant received additional therapeutic intervention or initiation of an alternative antihyperglycemic medication following study drug discontinuation (rescue therapy). Participants who received rescue therapy were included in the analysis population, but only measurements obtained prior to the beginning of rescue therapy were included in specified analyses.

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