Comparison of TAK-875 to Placebo as an Add-on to Glimepiride in Patients With Type 2 Diabetes

The drug being tested in this study is called TAK-875. TAK-875 is being tested to treat
people who have diabetes. This study will look at glycosylated hemoglobin (blood glucose
combined with hemoglobin, also known as HbA1c) and blood sugar levels in people who take
TAK-875 in addition to glimepiride and diet and exercise.

The study will enroll approximately 260 patients. Participants will be randomly assigned (by
chance, like flipping a coin) to one of the two treatment groups—which will remain
undisclosed to the patient and study doctor during the study (unless there is an urgent
medical need):

- TAK-875 50 mg

- Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has
no active ingredient.

All participants will be asked to take one tablet at the same time each day throughout the
study. This multi-center trial will be conducted in North America and Europe. The overall
time to participate in this study is up to 44 weeks and participants will make up to 17
visits to the clinic.

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and
complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable
representative signs and dates a written, informed consent form and any required
privacy authorization prior to the initiation of any study procedures.

3. Male or female and aged 18 or older with a historical diagnosis of type 2 diabetes
mellitus (T2DM).

4. Has a glycosylated hemoglobin (HbA1c) of 7.0% to10.0%, inclusive at screening, and
has been treated with diet and exercise and a sulfonylurea for at least 12 weeks.

5. Has a body mass index (BMI) ≤45 kg/m2 at Screening.

6. Participants regularly using other, non-excluded medications, must be on a stable
dose and regimen for at least 4 weeks prior to Screening. However, as needed (PRN)
use of prescription or over-the-counter medication is allowed at the discretion of
the investigator. Note: Participants who require initiation of a chronically
administered medication(s) due to a disease or condition diagnosed at Screening must
be re-screened after the new regimen has been stabilized.

7. A female of childbearing potential who is sexually active with a non-sterilized male
partner agrees to use routinely adequate contraception from signing of informed
consent throughout the duration of the study and for 30 days after the last dose of
study drug.

8. Is able and willing to monitor glucose with a sponsor-provided home glucose monitor
and consistently record his or her own blood glucose concentrations and participant
diaries.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to Screening or has
received an investigational antidiabetic drug within 3 months prior to Screening.

2. Has participated in a previous TAK-875 study.

3. Is an immediate family member, study site employee, or is in a dependant relationship
with a study site employee who is involved in conduct of this study (eg, spouse,
parent, child, sibling) or may consent under duress.

4. Has donated or received any blood products within 12 weeks prior to Screening or is
planning to donate blood during the study.

5. Has a hemoglobin ≤12 g/dL (≤120 gm/L) for males and ≤10 g/dL (≤100 gm/L) for females
at Screening.

6. Has a systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥95 mm Hg at
Screening (If the participant meets this exclusion criterion, the assessment may be
repeated once at least 30 minutes after the initial measurement and decision will be
made based on the second measurement).

7. Has a history of cancer that has been in remission for <5 years prior to Screening. A
history of basal cell carcinoma or stage 1 squamous cell carcinoma of the skin is
allowed.

8. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels
>2.0x the upper limit of normal (ULN) at Screening.

9. Has a total bilirubin level greater than the ULN at Screening. Exception: if a
participant has documented Gilbert's Syndrome, the participant will be allowed with
an elevated bilirubin level per the investigator's discretion.

10. Has a serum creatinine ≥1.5 mg/dL (≥133 μmol/L) [if male] or ≥1.4 mg/dL (≥124 μmol/L)
[if female] and/or estimated (based on Modification of Diet in Renal Disease [MDRD]
calculation) glomerular filtration rate (GFR) <60 mL/min/1.73m2 (regardless of
gender) at Screening.

11. Has uncontrolled thyroid disease.

12. Has a history of laser treatment for proliferative diabetic retinopathy within 6
months prior to Screening.

13. Has had gastric banding or gastric bypass surgery within 1 year prior to Screening.

14. Has known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency, which
increases risk for hemolytic anemia by sulfonylurea treatment.

15. Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B
virus (HBV), or hepatitis C virus (HCV).

16. Had coronary angioplasty, coronary stent placement, coronary bypass surgery,
myocardial infarction, unstable angina pectoris, clinically significant abnormal
electrocardiogram (ECG), cerebrovascular accident or transient ischemic attack within
3 months prior or at Screening.

17. Has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s)
to any component of TAK-875 or glimepiride.

18. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol
abuse within 2 years prior to Screening.

19. Received excluded medications prior to Screening or is expected to receive excluded
medication.

20. If female, the participant is pregnant (confirmed by laboratory testing, ie, serum
human chorionic gonadotropin (hCG), in females of childbearing potential) or
lactating or intending to become pregnant before, during, or within 1 month after
participating in this study; or intending to donate ova during such time period.

21. Is unable to understand verbal or written English or any other language for which a
certified translation of the approved informed consent is available.

22. Has any other physical or psychiatric disease or condition that in the judgment of
the investigator may affect life expectancy or may make it difficult to successfully
manage and follow the participant according to the protocol.