effect of ly2189265 on insulin secretion in response to intravenous glucose

Conditions: Diabetes Mellitus, Type 2

Summary: 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