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