12-Week, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Metformin DR in Subjects With Type 2 Diabetes Mellitus

Inclusion Criteria:

1. Male or female with type 2 diabetes who are ≥18 and ≤65 years of age at Visit 1.

2. Has a BMI of 25.0 kg/m2 to 45.0 kg/m2, inclusive, at Visit 1.

3. Screening HbA1c 7.0 to 9.5% (inclusive) at Visit 1 if treated with diet and exercise
alone, or 6.0 to 9.5% (inclusive) if on a stable dose of either metformin or DPP-4
inhibitor monotherapy for a minimum of 2 months at Visit 1, or a combination of these
2 agents only on a stable regimen for a minimum of 2 months at Visit 1.

4. Has serum creatinine below the upper limit of normal at Visit 1 and an estimated
glomerular filtration rate (eGFR) of ≥90 mL/min/1.73 m2 based on the Modification of
Diet in Renal Disease (MDRD) equation: eGFR (mL/min/1.73 m2) = 175 x (Scr, std)-1.154
x (Age)-0.203 x (0.742 if female) x (1.212 if African American).

5. Has a fasting glucose concentration of <280 mg/dL at Visit 1.

6. Has a stable body weight, i.e., not varying by >5% for at least 6 months prior to
Visit 1 as documented by the investigator.

7. Is male, or is female and meets all of the following criteria:

1. Not breastfeeding

2. Negative pregnancy test result (human chorionic gonadotropin, beta subunit
[βhCG]) at Visit 1 (not applicable to hysterectomized females)

3. If of child bearing potential (including perimenopausal women who have had a
menstrual period within 1 year), must practice and be willing to continue to
practice appropriate birth control (defined as a method which results in a low
failure rate, i.e., less than 1% per year, when used consistently and correctly,
such as implants, injectables, hormonal contraceptives, intrauterine
contraceptive devices (IUD), sexual abstinence, tubal ligation or occlusion,
condom with spermicide or a vasectomized partner) during the entire duration of
the study.

8. Has a physical examination and ECG with no clinically significant abnormalities as
judged by the investigator at Visit 1.

9. Has no clinically significant laboratory test values (clinical chemistry, hematology,
urinalysis) other than those expected in subjects with diabetes as judged by the
investigator at Visit 1.

10. Either is not treated with or has been on a stable treatment regimen with any of the
following medications for a minimum of 3 months prior to Visit 1:

1. Hormone replacement therapy (female subjects)

2. Oral contraceptives (female subjects)

3. Antihypertensive agents

4. Lipid-lowering agents

5. Thyroid replacement therapy

6. Antidepressant agents

11. If on chronic thyroid pharmacologic therapy, has a serum thyroid-stimulating hormone
(TSH) test result within the normal range at Visit 1.

12. Is willing and able to follow study procedures.

13. Is able to read, understand, and sign the Informed Consent Form (ICF) and an
Authorization to Use and Disclose Protected Health Information form (consistent with
Health Insurance Portability and Accountability Act of 1996 [HIPAA] legislation),
answer the study questions, communicate with the investigator, and understand and
comply with protocol requirements.

Exclusion Criteria:

1. Has a clinically significant medical condition that could potentially affect study
participation and/or personal well-being, as judged by the investigator, including
but not limited to the following conditions:

1. Hepatic disease

2. Renal disease

3. Gastrointestinal disease

4. Endocrine disorder except type 2 diabetes mellitus

5. Cardiovascular disease

6. Central nervous system diseases

7. Psychiatric or neurological disorders

8. Organ transplantation

9. Chronic or acute infection (e.g., tuberculosis, human immunodeficiency virus,
hepatitis B virus, or hepatitis C virus)

10. Orthostatic hypotension, fainting spells or blackouts

11. Allergy or hypersensitivity

2. Clinically significant malignant disease (with the exception of basal and squamous
cell carcinoma of the skin) within 5 years of Visit 1.

3. Has any chronic disease other than type 2 diabetes mellitus requiring medication that
has been adjusted in the past 90 days (subjects may take acute intermittent
over-the-counter medications such as Tylenol, if needed).

4. Has known hypersensitivity, intolerability, or allergies to metformin HCl or any
component of study treatment.

5. Has clinical laboratory test (clinical chemistry, hematology, or urinalysis) or ECG
abnormalities, other than those expected in subjects with diabetes, judged by the
investigator to be clinically significant at Visit 1.

6. Has physical, psychological, or historical finding that, in the investigator's
opinion, would make the subject unsuitable for the study.

7. Currently abuses drugs or alcohol or has a history of abuse that in the
investigator's opinion would cause the individual to be noncompliant with study
procedures.

8. Had major surgery or a blood transfusion within 2 months of Visit 1 or is planning to
donate blood during the study, or had a significant blood loss within 2 months prior
to Visit 1.

9. Has been treated, is currently being treated, or is expected to require or undergo
treatment with any of the following excluded medications:

1. Insulin or sulphonylurea treatment within 3 months of Visit 1.

2. GLP-1 receptor agonists and/or thiazolidinedione treatment within 6 months of
Visit 1.

3. Furosemide, Nifedipine, thiazides or other diuretics, or cationic drugs within 6
months of Visit 1.

4. Systemic corticosteroids by oral, intravenous, intra-articular, or
intra-muscular route within 30 days of screening or for more than 1 week within
3 months of Visit 1.

5. Prescription weight loss medications within 3 months of Visit 1.

6. Chronic or frequent use, in the judgment of the investigator, of any drug
treatment that affects gastric pH (prescription or over-the-counter), including
proton pump inhibitors or any antacids or medications such as Rolaids or Pepcid
within 1 month of Visit 1.

7. Has received or plans to receive any iodinated contrast dye within 1 week prior
to Visit 1 (Screening).

10. Has had a surgical gastrointestinal procedure that may impact the gut hormonal
response to study medication.

11. History or presence of inflammatory bowel disease or other severe gastrointestinal
disease, particularly those which may impact gastric emptying, such as gastroparesis,
pyloric stenosis, gastric bypass surgery or gastric banding surgery.

12. Has received any investigational drug within 30 days (or five half-lives of the
investigational drug, whichever is greater) of Visit 1.

13. Is an immediate family member (spouse, parent, child, or sibling; biological or
legally adopted) of personnel directly affiliated with the study at the clinical
study site, or is directly affiliated with the study at the clinical study site.

14. Is employed by Elcelyx Therapeutics, Inc. (that is an employee, temporary contract
worker, or designee responsible for the conduct of the study).