Targeting Inflammation Using Salsalate for Type 2 Diabetes-Stage II

Inclusion Criteria:

1. Type 2 diabetes on diet and exercise therapy or monotherapy with metformin, insulin
secretagogue (including SFU, non-SFU, and dipeptidyl peptidase IV (DPP-4) inhibitors),
alpha-glucosidase inhibitors, or bile acid sequestrants (dosed once per day such that
study drug can be administered ≥ 4 hours prior to sequestrant); or a combination of up
to two of these at maximal dose. Dosing must be stable for 8 weeks prior to screening.
Participant must have been diagnosed with T2D at least 8 weeks before screening.

2. FPG ≤ 225 mg/dL and HbA1c≥7% and ≤ 9.5% at screening.

3. Age ≥18 and <75

4. Women of childbearing potential agree to use an appropriate contraceptive method
(hormonal, IUD, or diaphragm)

Exclusion Criteria:

1. No prior participation in Stage I of TINSAL-T2D ; exception: a participant who failed
screening for HbA1c in Stage I will be allowed to re-screen for Stage II.

2. Type 1 diabetes and/or history of ketoacidosis determined by medical history

3. History of severe diabetic neuropathy including autonomic neuropathy, gastroparesis or
lower limb ulceration or amputation

4. History of long-term therapy with insulin (>30 days) within the last year

5. Therapy with rosiglitazone (Avandia) or pioglitazone (Actos), alone or in combination
in the previous 6 months; or exendin-4 (Byetta), alone or in combination in the
previous 3 months

6. Pregnancy or lactation

7. Patients requiring oral corticosteroids within 3 months or recurrent continuous oral
corticosteroid treatment (more than 2 weeks)

8. Use of weight loss drugs [e.g., Xenical (orlistat), Meridia (sibutramine), Acutrim
(phenylpropanol-amine), or similar over-the-counter medications] within 3 months of
screening or intentional weight loss of ≥ 10 lbs in the previous 6 months

9. Surgery within 30 days prior to screening

10. Serum creatinine >1.4 for women and >1.5 for men or eGFR <60 [possible chronic kidney
disease stage 3 or greater calculated using the Modification of Diet in Renal Disease
(MDRD) equation

11. History of chronic liver disease including hepatitis B or C

12. History of peptic ulcer or endoscopy demonstrated gastritis

13. History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)

14. History of malignancy, except participants who have been disease-free for greater than
10 years, or whose only malignancy has been basal or squamous cell skin carcinoma

15. New York Heart Association Class III or IV cardiac status or hospitalization for
congestive heart failure

16. History of unstable angina, myocardial infarction, cerebrovascular accident, transient
ischemic attack or any revascularization within 6 months

17. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg or diastolic
blood pressure >95 mmHg on three or more assessments on more than one day). If on
blood pressure medications, dosing should be stable for 2 weeks prior to
randomization.

18. History of drug or alcohol abuse, or current weekly alcohol consumption >10 units/week
(1 unit = 1 beer, 1 glass of wine, 1 mixed DCCktail containing 1 ounce of alcohol)

19. Hemoglobin <12 g/dL (males), <10 g/dL (females) at screening*

20. Platelets <100,000 cu mm at screening

21. AST (SGOT) >2.50 x ULN or ALT (SGPT) >2.50 x ULN at screening

22. Total Bilirubin >1.50 x ULN at screening

23. Triglycerides (TG) >500 mg/dL at screening

24. Poor mental function or any other reason to expect patient difficulty in complying
with the requirements of the study

25. Previous allergy to aspirin

26. Chronic or continuous use (daily for more than 7 days) of nonsteroidal
anti-inflammatory drugs within the preceding 2 months

27. Use of warfarin (Coumadin), clopidogrel (Plavix), dipyridamole (Persantine), heparin
or other anticoagulants

28. Use of probenecid (Benemid, probalan), sulfinpyrazone (Anturane) or other uricosuric
agents

29. Macroalbuminuria, defined as spot urine protein >300 mcg/mg Cr at screening

30. Pre-existing chronic tinnitus