Anti-Inflammatory Small Drug Adjunctive Therapy for Type 2 Diabetes

INCLUSION CRITERIA

• Patients 21-75 years of age inclusive who meet the American Diabetes Association standard criteria for type 2 diabetes mellitus (T2D).
• Subjects are currently on metformin (at least 1000 mg per day) for a minimum period of 4 weeks prior to screening visit alone, or in combination with any of the following diabetes medications or combinations:
• DPPIV inhibitor (any dose level/frequency)
• Sulfonylurea (any dose level/frequency)
• GLP1 agonist (any dose level/frequency)
• Sulfonylurea (any dose level/frequency) + GLP1 agonist (any dose level/frequency)
• Meglitinide (any dose level/frequency)
• SGLT2 inhibitor (any dose level/frequency)
• Patients must have a body-to-mass index (BMI) of greater than or equal to 27 kg/m2.
• Patients exhibit glycated HbA1c between 7.3-11.0 during eligibility screening and then 6 months between time of successful treatment confirmation and time at screening) would be eligible for enrollment in this trial.
• Patients are required by treating physician to remain on any medications listed in inclusion #2 that directly affect glucose metabolism such as, but not limited to thiazolidinediones, pramlintide, or amylin.
• Vaccination with any form of live vaccine product within the last 3 months prior to initiation of study agent administration.
• Any chronic disease that in the opinion of the investigators would affect the patient's safety and/or the integrity of the study outcome. This does not include dyslipidemia, patients on statin or anti- hypertension treatment, or patients with well-controlled hypo- or hyperthyroidism
• Any other disease or disorder requiring chronic drug therapy except for treated hypothyroidism (T4 and TSH should be within the normal reference range adjusted for age), celiac disease, or statin- maintained, uncomplicated lipidemia.
• Evidence of liver dysfunction, with ALT or AST> 1.5 times the upper limit of normal.
• Evidence of renal insufficiency as indicated by blood creatinine of > 2 times the upper limit of normal at baseline screening OR an eGFR < 45 mL/min. OR A past history or current clinical evidence of renal failure or low creatinine clearance at screening.
• Females who are pregnant at the time of screening or unwilling to defer pregnancy during the study period.
• Lactating women.
• Poor accessibility to veins for the 3-hour OGTT and hyperinsulinemic-euglycemic clamp procedures.
• The following therapies cannot be administered while patients are undergoing treatment on this protocol: i) radiation therapy; ii) chemotherapy; iii) corticosteroids (except for very short courses of topical or inhaled); iv) agents used to treat attention deficit and hyperactivity disorder (ADHD); v) rifampicin or phenytoin; vi) other protein, particle or cell vaccine immunomodulation therapies. If these therapies are essential for treatment of other conditions, participation in this study will be terminated.
• A condition which interferes with the ability to accurately determine glycated HbA1c. Examples include: Genetic variants (e.g. HbS trait, HbC trait), elevated fetal hemoglobin (HbF) and chemically modified derivatives of hemoglobin (e.g. carbamylated Hb in patients with renal failure); Any condition that shortens erythrocyte survival or decreases mean erythrocyte age (e.g., recovery from acute blood loss, hemolytic anemia); Iron deficiency anemia, iron replacement therapy
• Subjects who cannot tolerate at least 1000 mg daily of immediate or extended release metformin by the time of final run-in will be excluded from further participation.
• Subjects who do not exhibit a glycated HbA1c level <=8.5 by the end of the run-in period.