A Study in Participants With Type 2 Diabetes Mellitus (AWARD-3)

The purpose of this study is to determine if LY2189265 is safe and effective in reducing glycosylated hemoglobin (HbA1c) as compared to metformin in participants with Type 2 Diabetes.

The term rescue therapy in this trial was defined primarily as additional nontrial antidiabetic medication for the management of severe, persistent hyperglycemia or alternative antidiabetic medication following study drug discontinuation. For efficacy analyses, participants who received rescue medication were included in the analysis population, but only measurements obtained prior to taking rescue therapy were included in the efficacy analysis. For safety analyses, with the exception of hypoglycemia outcomes, all measurements including those obtained after taking rescue therapy were included in the analysis.

Eligibility Criteria:
Inclusion Criteria:

* Have type 2 diabetes for greater than or equal to 3 months and less than or equal to 5 years based on the disease diagnostic criteria (refer to the World Health Organization's \[WHO\] Classification of Diabetes).
* Are treatment-naïve, not optimally controlled with diet and exercise alone, or are taking 1 oral antihyperglycemic medication (OAM) as monotherapy (excluding thiazolidinediones). For those on 1 OAM, the dose must be less than or equal to 50% the maximum authorized per local label.
* Are able and willing to tolerate a minimum dose of 1500 milligrams per day (mg/day) or up to 2000 mg/day of metformin.
* Have glycosylated hemoglobin (HbA1c) greater than or equal to 6.5% to less than or equal to 9.5%.
* Females of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) must: a) test negative for pregnancy at screening based on a serum pregnancy test, and b) agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; or c) not be breastfeeding.
* Have a stable weight (plus or minus 5%) greater than or equal to 3 months prior to screening.
* Have a body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m\^2), inclusive.
* Are well-motivated, capable, and willing to: a) perform self-monitored blood glucose (SMBG) testing; b) learn how to self-inject treatment (LY2189265 or placebo) and c) maintain a study diary.

Exclusion Criteria:

* Have type 1 diabetes mellitus.
* Are being or have been treated with any of the following medications: a) chronically treated with insulin for the treatment of diabetes in the past; however, a short-term use of insulin more than 3 months prior to screening is allowable, b) glucagon-like peptide 1 (GLP-1) analogs within 3 months prior to this screening, c) drugs to cause weight loss within 3 months prior to screening, d) thiazolidinediones (TZDs) within 3 months prior to screening, e) chronically treated (greater than or equal to 14 days) with an oral glucocorticoid or have received this type of therapy within 4 weeks prior to screening, or f) illegal drugs.
* Have had 1 or more cases of uncontrolled diabetes that required hospitalization in the 6 months prior to screening.
* Have stomach problems, have chronically taken medication to increase movement in the digestive tract or slow down the emptying of the digestive tract, or have had gastric bypass (bariatric) surgery.
* Have had problems with the heart or brain in the past 2 months prior to screening, such as a heart attack, chest pain, heart failure, heart bypass operation, angioplasty or stent insertion, a heart rhythm problem, or a stroke.
* Have a serum creatinine result which shows a greater than or equal to 1.5 milligrams per deciliter (mg/dL) for men or greater than or equal to 1.4 mg/dL for women.
* Have a problem with the liver or pancreas.
* Have a creatinine clearance result which shows less than 60 milliliters per minute (mL/min), evidence of a significant active, uncontrolled endocrine (hormone), or active autoimmune abnormality.
* Have a serum calcitonin test which shows greater than or equal to 20 picograms per milliliter (pcg/mL) at the time of screening.
* Have a family history of medullary C-cell hyperplasia or endocrine neoplasia type 2A or type 2B.
* Have cancer (except for skin cancer) or have been in remission from cancer for less than 5 years.
* Have had an organ transplant except for corneal transplant.
* Have received treatment within the last 30 days with a drug which has not been regulatory approved.
* Have participated in a medical, surgical, or pharmaceutical study where these types of procedures were performed within 30 days prior to screening.
* Have any condition that is a contraindication to or would interfere with medications provided for this study to treat diabetes.
* Have a blood disorder that would interfere with the drawing of blood glucose measurements or lab samples.
* Have previously participated or signed an informed consent document for this same type of study and study drug.