The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year Medalist Study ("Medalists"), who are characterized by ≥50 years of insulin-dependent diabetes. Our primary objective is to evaluate whether the presence of human leukocyte antigen (HLA) high-risk alleles for diabetes (DR3 and/or DR4) can affect the effectiveness of OHA in these subjects.

Inclusion Criteria:

• Existing participants in the Joslin 50-Year Medalist Study
• Residing in the United States
• Capable of giving informed consent
• Known detectable C-peptide >0.05 ng/mL

Exclusion Criteria:

• Known diagnosis of cancer or active inflammatory disease such as rheumatoid arthritis, lupus, and inflammatory bowel disease
• Recent history of myocardial infarction, angioplasty, bypass surgery, heart failure, angina, stroke, or uncontrolled hypertension>160/100 during the past 3 months
• Known diagnosis of cognitive dysfunction, dementia or Alzheimer's disease
• Pre-existing liver disease or liver function tests (AST or ALT)>3x the upper limit of normal
• Pre-existing kidney disease (Chronic Kidney Disease Stage IV and below, or estimated glomerular filtration rate<45 mL/min/1.73 m2)
• Active use of immunosuppressants
• Recipients of prior islet cell or pancreas transplantation
• Inability to travel due to frailty or health reasons
• Donated blood within the previous two (2) months