A Study to Test the Combination of Two Different Kinds of Medications for the Treatment of Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: LY2428757; TT223; Placebo for LY2428757; Placebo for TT223
Intervention description: 14 mg subcutaneous injection 1 time a week for 5 weeks; subcutaneous injection once a day for 4 weeks; subcutaneous injection 1 time a week for 5 weeks; subcutaneous injection once a day for 4 weeks
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      Test the safety, tolerability and improvement of blood sugar control with combination therapy
      in individuals with Type 2 Diabetes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Have type 2 diabetes mellitus (T2DM) for at least 6 months

          -  Currently treated with diet and exercise alone or in combination with stable metformin

          -  Glycosylated hemoglobin (HbA1c) 7.0% to 10.0%

          -  Ages 18 to 70 years

          -  Women not of childbearing potential

          -  Body mass index (BMI) between 25 and 40 kilograms per meters squared (kg/m^2), and
             stable weight in the 3 months prior to screening.

        Exclusion Criteria:

          -  Use of diabetes medicine other than metformin in past 3 months

          -  Gastrointestinal disease or surgery or drugs that significantly impacts gastric
             filling, emptying or motility; ongoing cholelithiasis or cholecystitis.

          -  Chronic, daily proton pump inhibitors (PPIs) and histamine (H2) antagonists.

          -  Severe hypoglycemia or hyperglycemia

          -  Advanced microvascular diabetes complications

          -  Medications to promote weight loss.

          -  Breastfeeding women

          -  Cardiac autonomic neuropathy

          -  In the past 6 months have cardiac disease with functional status that is Class II-IV
             or a history of myocardial infarction, unstable angina, coronary artery bypass graft,
             percutaneous coronary intervention, transient ischemic attack, cerebrovascular
             accident (stroke), or decompensated congestive heart failure.

          -  History of a supraventricular or ventricular tachycardia, pacemaker implantation, or
             other cardiac arrhythmia: Poorly controlled hypertension, malignant hypertension,
             renal artery stenosis, and/or evidence of labile blood pressure including symptomatic
             postural hypotension.

          -  Electrocardiograms (ECG) abnormality or medication that impairs the ability to measure
             QT interval (QT), or correct the QT interval (QT) for rate.

          -  QT interval Bazett corrected (QTcB) >450 milliseconds (msec) or PR interval (PR) >220
             milliseconds (msec)

          -  Personal or family history of long QT interval (QT) syndrome, sudden death, or
             unexplained syncope

          -  Clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine
             transaminase levels > 2.5 times the upper limit of the reference range

          -  Hypertriglyceridemia > 400 mg/deciliter (dL)

          -  Inadequately treated hypothyroidism or hyperthyroidism

          -  Peptic ulcer disease and/or gastrointestinal bleeding/perforation.

          -  Known pentagastrin hypersensitivity

          -  Impaired renal function

          -  Transplanted organ.

          -  Active, uncontrolled endocrine or autoimmune abnormality

          -  > 2 weeks systemic glucocorticoid therapy

          -  Ongoing courses of non-steroidal anti-inflammatory drugs (NSAIDs), except for aspirin
             81-325 milligrams (mg)

          -  Diagnosed malignancy or in remission for less than 5 years.

          -  Prior acute or chronic pancreatitis or elevated serum lipase or amylase

          -  Current central nervous system stimulant

          -  Other conditions that preclude the participant from participating, following or
             completing the protocol.

          -  Chronic infection

          -  Personnel affiliated with the study and their immediate families.

          -  Within 30 days of the initial dose of study drug, have participated in an
             interventional medical, surgical, or pharmaceutical study in which a medical or
             surgical treatment was given.

          -  Have previously completed or withdrawn from this study after providing informed
             consent.

          -  Are currently enrolled in, or discontinued within the last 30 days from, a clinical
             trial involving an off-label use of an investigational drug or device (other than the
             study drug/device used in this study), or concurrently enrolled in any other type of
             medical research judged not to be scientifically or medically compatible with this
             study.