A Study to Test the Combination of Two Different Kinds of Medications for the Treatment of Diabetes

A Proof of Concept Study to Evaluate the Coadministration of TT223 Given Daily and LY2428757 Given Once-Weekly for Four Weeks in Patients With Type 2 Diabetes Mellitus

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

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.