Warfarin is a commonly used drug to prevent the blood from clotting. The purpose of this study is to determine if dulaglutide (LY2189265) affects how warfarin works. The study involves two different treatments (Treatment 1: warfarin; Treatment 2: dulaglutide + warfarin) separated by a minimum washout period of 24 days. In Treatment 1, the participant will receive 10 milligrams (mg) of warfarin on Day 1. In Treatment 2, the participant will receive a 1.5-mg dose of dulaglutide (LY2189265) as an injection on Day 1 and then a 10 mg dose of warfarin on Day 3. Participants will be randomly assigned into different treatment sequences. Participants in Treatment Sequence A will receive Treatment 1 then Treatment 2. Participants in Treatment Sequence B will receive Treatment 2 then Treatment 1.

Inclusion Criteria:

• male participants with female partners of child-bearing potential, or partners who are pregnant or breastfeeding, agree to use a reliable method of contraception from the time of the first dose until 3 months after the last dose of investigational product, as determined by the investigator. The method may be one of the following:

  • condom with spermicidal agent
  • male participant sterilization
  • true abstinence (which is in line with the participant's usual lifestyle choice; withdrawal or calendar methods are not considered acceptable)

• female participants not of child-bearing potential and are postmenopausal or have undergone a documented hysterectomy (total or partial). Such participants will not be required to use contraception but must test negative for pregnancy at the time of enrolment. Postmenopausal is defined as at least 1 year post cessation of menses (without an alternative medical cause) with follicle stimulating hormone (FSH) ≥40 milli-international units per milliliter (mIU/mL)

• have a body mass index (BMI) of 18.5 to 32.0 kilograms per meter squared (kg/m^2), inclusive, at screening

• have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator

• have venous access sufficient to allow for blood sampling

• are reliable and willing to make themselves available for the duration of the study and are willing to follow study restrictions

• have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site

Exclusion Criteria:

• are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• have known allergies to glucagon-like-peptide 1 (GLP-1)-related compounds including dulaglutide or to warfarin, related compounds, or any components of either formulation
• are persons who have previously completed or withdrawn from this study or any other study investigating dulaglutide in the 3 months prior to screening or have received glucagon-like peptides or incretin mimetics in the 3 months prior to screening
• history or presence of significant bleeding disorders that is, hematemesis, melena, severe or recurrent epistaxis, hemoptysis, hematuria, or intracranial hemorrhage
• have a personal history, family history, or current evidence of a bleeding disorder, coagulopathy, or clinically significant history of bleeding complications after surgical procedures, tooth extractions, nose or gingival bleeding, spontaneous bleeding (including bleeding into joint spaces)
• have a personal or family history of polycystic kidney disease or protein C or S deficiency
• have a history of major head trauma (with loss of consciousness) within the past year or minor head trauma (without loss of consciousness) within the last 3 months prior to screening
• have a history of or plan to undergo major surgery in the last 3 months prior to screening
• show positive for a fecal occult blood test at screening
• have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
• have an abnormal blood pressure (after at least 5 minutes sitting) that, in the opinion of the investigator, increases the risks associated with participating in the study
• have a history or presence of cardiovascular, respiratory, hepatic, renal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
• have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis) or gastrointestinal disorder, for example relevant esophageal reflux or gall bladder disease, or any gastrointestinal disease which impacts gastric emptying (GE) (such as, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by GLP-1 analogs. Participants with mild dyslipidemia, and participants who had cholecystolithiasis (removal of gall stones) and/or cholecystectomy (removal of gall bladder) in the past, with no further sequelae, may be included in the study at the discretion of the screening physician
• Show evidence of significant active neuropsychiatric disease
• have family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC
• regularly use known drugs of abuse and/or show positive findings on urinary drug screening
• show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
• show evidence of hepatitis C and/or positive hepatitis C antibody
• show evidence of hepatitis B and/or positive hepatitis B surface antigen
• are women with a positive pregnancy test or women who are lactating
• have used or intend to use over-the-counter medication other than acetaminophen within 7 days prior to the first dose of warfarin or dulaglutide or prescription medication (with the exception of vitamin/mineral supplements and/or hormone replacement therapy [HRT]) within 14 days prior to dosing. Aspirin and other nonsteroidal anti-inflammatory drugs should not be taken from 2 weeks prior to the first dosing occasion
• show intended use of any drug or dietary supplement that may affect warfarin or coagulation within 14 days prior to the first dose of warfarin or dulaglutide or during the conduct of the study
• use or intended use of a drug that inhibits or induces cytochrome P450 (CYP)1A2, CYP2C9, CYP2C19, or CYP3A4 within 14 days prior to the first dose of warfarin or dulaglutide or during the conduct of the study
• have donated blood of more than 500 milliliters (mL) within the month prior to screening
• have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females), or are unwilling to stop alcohol consumption from 48 hours prior to admission (Day -1 of the first treatment period) until discharge (1 unit = 12 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
• are smokers
• have an international normalized ratio/prothrombin time (INR/PT) or activated partial thromboplastin time (aPTT) above the normal reference range at screening
• are females who menstruate
• have consumed grapefruit, cranberries, or grapefruit- or cranberry-containing products within 7 days prior to the first dose of warfarin or dulaglutide
• in the opinion of the investigator or sponsor, are unsuitable for inclusion in the study
• have any medical conditions, medical history or are taking any medication which are contraindicated within the warfarin Product Information Leaflet

Participants who received at least 1 dose of study drug (dulaglutide or warfarin).