Study of Subcutaneous Doses of HIP2B in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

Inclusion Criteria:

- Adults aged 30 to 65 years, inclusive

- Males and females

- Diagnosis of type 2 diabetes mellitus prior to screening meeting the following
criteria:

1. Body mass index <45 kg/m2

2. HbA1c value of > 6.5 to <9.5%

3. C-peptide ≥1.0 ng/mL

4. On a stable dose of metformin for 12 weeks

- Ability to provide written informed consent and be willing to comply with scheduled
visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria:

- History of any of the following: type 1 diabetes mellitus, diabetic ketoacidosis, an
episode of severe hypoglycemia (defined as a change in mental status requiring
assistance) during the prior 30 days

- FPG >260 mg/dL at time of randomization

- Current or chronic use (within past 12 weeks) of insulin, or insulin secretagogues
including: sulfonylureas, GLP-1 analogs, DPP-4 inhibitors, meglitinides,
α-glucosidase inhibitors, pioglitazone, or rosiglitazone

- Glomerular filtration rate (GFR) <60 as calculated using the Modified Diet in Renal
Disease equation at screening

- ALT, AST or total bilirubin > 2 X ULN

- Serum amylase concentration > 1.5XULN or serum lipase concentration >2XULN

- Positive test result for glutamic acid decarboxylase antibodies (GADA).

- The presence of a clinically significant abnormality on resting electrocardiogram
(ECG)

- Positive HIV, hepatitis B (HBsAg), or positive hepatitis C (HCV Ab) test at screening

- History of clinically significant renal, hepatic, cardiovascular, neurological, or
gastrointestinal disease that could impact patient safety in the investigator's
opinion

- Serum triglycerides >500 mg/dL

- Presence or history of cancer within the past 5 years with the exception of
adequately treated localized basal cell skin cancer or in situ uterine cervical
cancer

- History of weight loss > 5% in the 8 weeks prior to randomization or subject is on a
weight loss program and is not in the maintenance phase

- Use of any weight loss medication within 8 weeks of randomization

- Uncontrolled hypertension defined as blood pressure >160/100 mmHg, using an
appropriately sized cuff, at rest

- History or evidence of multiple organ autoimmune disorders

- History of thyroid dysfunction other that hypothyroidism treated with stable dose of
thyroid hormone and euthyroid at screening

- History or presence of acute or chronic pancreatitis or symptomatic recurrent
gallstones

- Has undergone surgery within 6 months of screening or plans to undergo surgery during
the study period

- Use of parenterally administered proteins or antibodies within 12 weeks of screening.
(Note: Influenza vaccine will be allowed.)

- Prior exposure to any investigational agent or participation in an investigational
trial within 30 days prior to Day 1

- Blood loss or blood donation >500 ml in the 2 months prior to screening.

- Use of systemic long-acting corticosteroids within two months or prolonged use (more
than one week) of other systemic corticosteroids or inhaled corticosteroids (if daily
dosage is >1000 mcg equivalent beclomethasone) within 30 days prior to screening
visit.

- Drugs with the potential to affect (either increasing or decreasing) endogenous
insulin secretion or insulin sensitivity including corticosteroids (as detailed
above), β-adrenergic blockers, beta-adrenergic agonists, quinine, thiazide or
thiazide-like diuretics, calcineurin inhibitors, niacin, anti-psychotic or
antidepressant drugs, somatostatin analogs, growth hormone, weight-reducing drugs
(e.g. orlistat, phentermine and topiramate extended-release, lorcaserin). Stable
doses of agents commonly required by subjects with T2DM including angiotensin
converting enzyme inhibitors, angiotensin II receptor blockers, statins, fibrates,
and aspirin (<100 mg daily) will be permitted at the discretion of the investigator.

- A serious adverse reaction or hypersensitivity to any drug, unless reaction deemed
irrelevant to the study by the investigator and sponsor.

- History of alcohol abuse or drug abuse within the previous 12 months. No history of
medical or recreational use of marijuana within previous 12 months.

- A history of smoking more than one-half a pack of cigarettes per day within last 12
months

- History of stroke, transient ischemic attack or myocardial infarction within 6 months
prior to screening.

- History of New York Heart Association Class II-IV heart failure prior to screening.