Evaluation of Superiority of Valsartan+Celecoxib+Metformin Over Metformin Alone in Type 2 Diabetes Patients

Exclusion Criteria

• •1. Age \>70
• •2. Patients with Type 1 diabetes, Screen for GAD (Glutamic acid decarboxylase) antibodies at the time of screening visit. To rule out latent autoimmune diabetes in adults (LADA), screening for other diabetes-related antibodies, such as insulinoma-associated protein (IA-2 and IA-2 beta), zinc transporter-8 (ZnT8), islet cell antibodies (ICA) or insulin autoantibody (IAA) will also be considered.
• •3. Pregnant women
• •4. Patients with a history of Ketoacidosis.
• •5. Subjects at serious risk of gastrointestinal (GI) adverse events (e.g. current or recent history of GI bleeding ulceration, or perforation).
• •6. Subjects with a planned radiologic study with intravenous contrast, surgery, or other planned procedures that may predispose them to metformin-associated lactic acidosis.
• •7. Insulin dependent: \<25% Beta-cell function: AIRg (Acute insulin response to glucose after 2 min and 10 min after glucose injection) INSULIN DEPENDENT STATE.
• •8. Patients with a history of uncontrolled hyperglycemia \>15.0 mmol/L (280 mg/dL) after an overnight fast that required rescue therapy.
• •9. Patients with uncontrolled hyperglycemia \>15.0 mmol/L (280 mg/dL) after an overnight fast that required rescue therapy during week 1-3 Metformin-HCl monotherapy or RK-01 therapy.
• •10. eGFR, impaired kidney function \< 60 ml/min/1.73m2.
• •11. Poor metabolizers of Cyp450 2C9 to avoid very high concentration (Since Cytochrome 450 2C9 is responsible for the metabolism of both Valsartan and Celecoxib, patients who are known or suspected to be poor Cyp450 2C9 metabolizers based on previous history will be excluded from the study).
• •12. Any of the following cardiovascular (CV)/Vascular diseases within 3 months of the enrollment visit:
• •1. Myocardial infarction (MI)
• •2. Cardiac surgery or revascularization (coronary artery bypass surgery, Coronary Artery Bypass Graft \[(CABG\]/Percutaneous transluminal coronary angioplasty (PTCA)\].
• •3. Unstable angina
• •4. Unstable congestive heart failure (CHF)
• •5. Transient ischemic attack (TIA) or significant cerebrovascular disease
• •6. Unstable or previously diagnosed arrhythmia
• •7. Congestive heart failure, defined as New York Heart Association (NYHA) Class III and IV, unstable or acute heart failure and/or known left ventricular ejection fraction of ≤40%.
• •8. Acute coronary syndrome, stroke or transient ischemic attack within 3 months prior to the informed consent.
• •13. Previous bariatric surgery
• •14. Treatment with anti-obesity drugs within 3 months prior to consent
• •15. Patients with COPD
• •16. Patients with liver disease
• •17. Patients with renal disease
• •18. Patients with autoimmune diseases e.g. Lupus, Psoriasis
• •19. Patients with HIV/AIDS
• •20. Patients with diabetes-related complications
• •21. Patients with Hematological and Oncological Diseases/Conditions
• •22. Hemoglobin \<11.0 g/dL (110 g/L) for men; hemoglobin \<10.0 g/dL (100 g/L) for women
• •23. Patients with chronic disease e.g. Cancer, Epilepsy, Alzheimer, Parkinson, Asthma
• •24. Abnormal free T4
• •25. Patients with serious infection