A Phase 3, Randomized, Double-blind, Parallel-group, Comparative Study and a Phase 3, Multicenter, Open-label, Long-term Study of SYR-472 (25 mg) in Patients With Type 2 Diabetes Mellitus Complicated by Severe Renal Impairment or End-stage Renal Failure

This is a phase 3, multicenter, randomized, double-blind, parallel-group, comparative study
(Treatment Period I) and a phase 3, multicenter, open-label, long-term study (Treatment
Period II) using placebo as a control to evaluate the efficacy and safety of SYR-472 when
administered orally at a dose of 25 mg once weekly to patients with type 2 diabetes mellitus
complicated by severe renal impairment or end-stage renal failure and inadequate glycemic
control despite diet and/or exercise therapy (if given) or despite treatment with one other
antidiabetic drug in addition to diet and/or exercise therapy (if given).

Inclusion Criteria:

- 1. The participant has a diagnosis of type 2 diabetes mellitus. 2. The participant
has a fasting C-peptide level of 0.6 ng/mL or higher at the start of the screening
period (Week -6) and Week -2 of the screening period.

3. The participant has a hemoglobin value of 10.0 g/dL or higher at the start of the
screening period (Week -6) and Week -2 of the screening period.

4. The participant has an HbA1c value of 7.0% or higher but less than 10.0% at Week
-2 of the screening period.

5. The participant has an HbA1c value difference between the start of the screening
period (Week -6) and Week -2 of the screening period within 10.0%* of the HbA1c value
at the start of the screening period (Week -6).

- rounded to one decimal place 6. The participant has been on a fixed diet and/or
exercise therapy (if given) from at least 6 weeks prior to the start of the
screening period (Week -6).

7. The participant meets any of the following:

- The participant has not received any antidiabetic medications (including
insulin preparations) from at least 6 weeks prior to the start of the
screening period (Week -6).

- The participant is being treated with one oral hypoglycemic drug* starting
from at least 6 weeks prior to the start of the screening period (Week -6)
at a fixed dose and regimen.

- any one of the following medications: mitiglinide calcium hydrate, repaglinide,
acarbose, miglitol, or voglibose

- The participant is being treated with one insulin preparation** starting
from at least 6 weeks prior to the start of the screening period (Week -6)
at a fixed dose and regimen (≤40 units/day) of the insulin preparation.

- Any one of the following insulin monotherapies: mixed (rapid-acting or
short-acting insulin containing no more than 30% volume),
intermediate-acting, or long-acting soluble insulin preparations 8.
The participant is not undergoing hemodialysis or peritoneal dialysis
and has severe renal impairment [creatinine clearance (Ccr) <30 mL/min
at the start of the screening period (Week -6)], or the participant is
undergoing hemodialysis and has end-stage renal failure.

9. In the opinion of the investigator or subinvestigator, the
initiation of hemodialysis or peritoneal dialysis at least within 12
weeks after starting the investigational product is not expected. [in
cases where the participant is not undergoing hemodialysis or
peritoneal dialysis (patients with severe renal impairment)] 10. The
participant has been undergoing hemodialysis starting from at least 6
months prior to informed consent and, in the opinion of the
investigator or subinvestigator, the participant is clinically stable.
[in cases where the participant is undergoing hemodialysis (patient
with end-stage renal failure)] 11. The participant is male or female
and is aged 20 years or older at the time of informed consent.

12. A female participant of childbearing potential who is sexually
active with a nonsterilized male partner agrees to use routinely
adequate contraception from signing of informed consent until one
month after the end of the study.

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

14. The participant signs and dates a written, informed consent form
prior to the initiation of any study procedures.

Exclusion Criteria:

- 1. The participants has clinically evident hepatic impairment [e.g., AST or ALT ≥2.5
times the upper limit of normal or total bilirubin of ≥2.0 mg/dL at the start of the
screening period (Week -6) or at Week -2 of the screening period].

2. The participant has any serious cardiac diseases, cerebrovascular disorders, or
serious pancreatic or hematological diseases (e.g., participants who require
inpatient treatment or are hospitalized for treatment within 24 weeks prior to the
start of the screening period).

3. The participant has severe ketosis, diabetic coma or pre coma, type 1 diabetes,
severe infection, before or after surgery, or severe external injury.

4. The participant has hemoglobinopathy (sickle cell disease, thalassemia, etc.).

5. The participant experienced hypoglycemia (participants with a blood glucose level
of ≤70 mg/dL or hypoglycemic symptoms) within 6 weeks prior to the start of the
screening period or during the screening period (at least twice per week).

6. The participant has inadequately controlled hypertension. 7. For participants who
are being treated with one antidiabetic agent, the participant was using at least two
antidiabetic therapies on the day before 6 weeks prior to the start of the screening
period (Week -6) (43 days prior to the start of the screening period).

8. The participant has malignancies. 9. The participant has a history of
hypersensitivity or allergies to dipeptidyl peptidase 4 (DPP-4) inhibitors.

10. The participant has a history of gastrectomy or small intestinal resection. 11.
The participant is a habitual drinker and consumes a daily average of more than 100
mL of alcohol.

12. The participant has a history of drug abuse (defined as the use of an illegal
drug) or alcohol dependence.

13. The participant is required to take excluded medications during the study period.

14. The participant has received SYR-472 in a previous clinical study. 15. The
participant received any other investigational products (including study drugs in a
post-marketing clinical study) within 12 weeks prior to the start of the screening
period.

16. The participant is participating in other clinical studies at the time of
informed consent.

17. If female, the participant is pregnant or lactating or intending to become
pregnant from the time of informed consent to within 1 month after the end of the
study; or intending to donate ova during such time period.

18. The participant is an immediate family member, study site employee, or is in a
dependent relationship with a study site employee who is involved in the conduct of
this study (e.g., spouse, parent, child, sibling) or may consent under duress.

19. The participant is hospitalized during the screening period or is deemed as
requiring hospitalization during the study period by the investigator or
sub-investigator, unless the hospitalization is for short-term evaluations including
complete health checkups.

20. The participant is deemed ineligible for the study for any other reason by the
investigator or sub-investigator.