Targeting Beta Cell Dysfunction With Liraglutide or Golimumab in Longstanding T1D

Inclusion criteria

• ≥ 3 years from Type 1 diabetes diagnosis
• Males and females 18-50 years of age, inclusive
• Peak MMTT stimulated C-peptide <0.017 pmol/mL
• Proinsulin levels ≥ 2 pM (either fasting or stimulated)
• Females of child-bearing potential must be willing to use effective birth control for 12 weeks
• Willing and able to give informed consent for participation
• HbA1c ≤ 8.5%

Exclusion criteria

• Concurrent use of non-insulin therapies aimed to control hyperglycemia or use within the past 30 days of screening MMTT (V-2).
• History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies.
• Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT or AST> 1.5 x the upper limit of age-determined normal (ULN) .
• Females who are pregnant or lactating.
• Receipt of an immune modulating biologic or investigational drug within 3 months or 5 half-lives before enrollment.
• History of other clinically significant autoimmune disease needing chronic therapy with biologics or steroids with the exception of celiac and stable thyroid disease.
• Current use of any medication known to significantly influence glucose tolerance (e.g. oral steroids, atypical antipsychotics, diphenylhydantoin, niacin).
• Any medical or psychological condition that in the opinion of the principal investigator would interfere with the safe completion of the trial.
• For Study A (liraglutide)

• Any history of pancreatitis or elevated amylase or lipase.
• Any personal or family history of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC).
• Any personal or family history of multiple endocrine neoplasia syndrome type 2.
• Hypersensitivity to liraglutide.
• Previous treatment with liraglutide.
• Known history of clinically significant gastroparesis.
• For Study B (golimumab)

• Any history of recent (within 3 months) serious bacterial, viral, fungal, or other opportunistic infections.
• Any history of demyelinating diseases (such as multiple sclerosis), heart failure, or left ventricular dysfunction.
• Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.
• Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection.
• Active infection with EBV, defined by real-time PCR.
• Active infection with CMV, defined by real-time PCR.
• Any of the following hematologic abnormalities at screening:

• White blood count <3,000/μL or >14,000/μL
• Lymphocyte count <500/μL
• Platelet count <140,000 /μL
• Hemoglobin <8.5 g/dL
• Neutrophil count <2,000 cells/μL
• Receipt of live vaccine (in the 6 weeks before treatment)