Effect of LY2189265 on Insulin Secretion in Response to Intravenous Glucose

The purpose of this study is to measure the effect of LY2189265 to increase insulin levels in response to glucose intake.


Eligibility Criteria:
Inclusion Criteria:

All Participants

* Women must be surgically sterile (hysterectomy or bilateral oophorectomy or tubal ligation) or postmenopausal as defined by age \>45 years without use of oral contraceptive agents for greater than 1 year and have either:

  * spontaneous amenorrhea greater than 12 months, or
  * spontaneous amenorrhea 6 to 12 months with documented follicle stimulating hormone (FSH) \>25 milli international units/milliliter (mIU/mL) and serum estradiol \<73 picomoles/liter (pmol/L) (20 picograms/milliliter \[pg/mL\])
* Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
* Have given written informed consent approved by Lilly and the ethical review board governing the site
* Have serum creatinine \<150 micromoles/liter (µmol/L) (\<1.3 milligrams/deciliter \[mg/dl\] in women, \<170 µmol/L \[\<1.5 mg/dL\] in men)
* Have normal hemoglobin result, as determined by the investigator

Healthy Participants

* Overtly healthy men and women as determined by medical history, normal lab results and physical examination.
* Body mass index (BMI) between 19 and 25 kilograms/meter squared (kg/m\^2), inclusive.
* Normal blood pressure and heart rate as determined by the investigator
* Have a normal response to an oral glucose tolerance test (OGTT) (glucose \<7.8 millimoles/liter \[mmol/L\] \[\<140 mg/dL\] at 2 hours after 75 grams (g) oral glucose load)

Participants with type 2 diabetes mellitus (T2DM)

* Participants will have a BMI between 22.0 and 40.0 kg/m\^2
* Have T2DM controlled with diet and exercise alone or metformin for at least 4 weeks prior to admission
* Have a hemoglobin A1c (HbA1c) value at screening (or within 4 weeks prior to screening) of 6.0% to 9.5%
* Diagnosed with T2DM within the past 10 years
* Clinical laboratory test results within normal range or deemed clinically insignificant by the Investigator. Abnormalities of serum glucose, serum lipids, urinary glucose, and urinary protein consistent with T2DM are acceptable.
* Participants who are taking stable-dose prescription medications (for example, antihypertensive agents, aspirin, lipid-lowering agents) for treatment of concurrent medical conditions are permitted to participate providing the medication is not associated with development of torsade de pointes. However, use of beta-blockers and thiazide diuretics are not permitted during this study.

Exclusion Criteria:

All Participants

* Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication
* Known allergies to Glucagon-Like Peptide 1 (GLP-1) related compounds
* Have previously completed or withdrawn from this study or any other study in the last year investigating glucagon-like peptides or incretin mimetics including exenatide (Byetta®)
* Regular use of known drugs of abuse and/or positive findings on urinary drug screening, other than findings consistent with medication prescribed by the participant's physician(s)
* History or presence of cardiovascular, respiratory, renal, endocrine (except T2DM), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data
* Have a history or presence of gastrointestinal disorder
* Poorly controlled hypertension (systolic greater than 160 millimeters of mercury \[mmHg\], diastolic greater than 95 mmHg) and/or evidence of labile blood pressure including symptomatic postural hypotension. Use of beta-blockers or thiazide diuretics is not permitted during the study
* Have a clinically significant history of cardiac disease or presence of active cardiac disease within 1 year of the screening period
* Evidence of hepatitis C and/or positive hepatitis C antibody
* Evidence of hepatitis B and/or positive hepatitis B surface antigen
* Evidence of human immunodeficiency virus (HIV) and/or positive for HIV antibodies
* Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) or are unwilling to follow alcohol restrictions (1 unit = 12 ounces \[oz\] or 360 milliliters\[mL\] of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
* Smoke more than 10 cigarettes or equivalent in nicotine use or nicotine substitutes per day
* Regular use of systemic corticosteroids by oral, intravenous, or intramuscular route, or potent, inhaled, or intranasal steroids known to have a high rate of systemic absorption
* Have a history or presence of significant active neuropsychiatric disease
* Blood donation of more than 500 mL in the last 3 months or any blood donation within the last month
* Any other condition, which in the opinion of the investigator would preclude participation in the study
* An abnormality in the 12-lead electrocardiogram (ECG) that in the opinion of the investigator increases the risk of participating in the study.
* Any clinically significant abnormal hematology, clinical chemistry, or urinary result(s) as determined by the investigator
* Evidence of significant active uncontrolled endocrine or autoimmune abnormalities (for example thyroid disease, or pernicious anemia) as judged by the screening physician

Healthy Participants

* Intended use of over-the-counter or prescription medication 7 and 14 days, respectively, prior to dosing.

Participants with T2DM

* Clinically significant peripheral vascular occlusive disease (PVOD).
* Known severe exudative diabetic retinopathy
* Known significant autonomic neuropathy as evidenced by urinary retention, diabetic diarrhea, or gastroparesis
* Have experienced a ketoacidotic episode (pH less than 7.3) requiring hospitalization in the last 6 months
* Outpatient use of insulin for control of diabetes within the past 2 years
* Use of antidiabetic agents other than metformin in the 4 weeks prior to study entry or use of thiazolidinediones within 12 weeks of study entry