Targeting Beta Cell Dysfunction With Liraglutide or Golimumab in Longstanding T1D

Inclusion Criteria:

1. ≥ 3 years from Type 1 diabetes diagnosis

2. Peak MMTT stimulated C-peptide <0.017 pmol/mL

3. Proinsulin levels ≥ 2 pM (either fasting or stimulated)

4. Females of child-bearing potential must be willing to use effective birth control for
12 weeks

5. Willing and able to give informed consent for participation

6. HbA1c ≤ 8.5%

Exclusion Criteria:

1. Concurrent use of non-insulin therapies aimed to control hyperglycemia or use within
the past 30 days of screening MMTT (V-2).

2. History of severe reaction or anaphylaxis to human, humanized or murine monoclonal
antibodies.

3. Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT, AST, or
both > 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin > ULN.

4. Females who are pregnant or lactating.

5. Receipt of an immune modulating biologic or investigational drug within 3 months or 5
half-lives before enrollment.

6. History of other clinically significant autoimmune disease needing chronic therapy
with biologics or steroids with the exception of celiac and stable thyroid disease.

7. Current use of any medication known to significantly influence glucose tolerance (e.g.
oral steroids, atypical antipsychotics, diphenylhydantoin, niacin).

8. Any medical or psychological condition that in the opinion of the principal
investigator would interfere with the safe completion of the trial.

9. For liraglutide arm

1. Any history of pancreatitis or elevated amylase or lipase.

2. Any personal or family history of thyroid C-cell tumors, including medullary
thyroid carcinoma (MTC).

3. Any personal or family history of multiple endocrine neoplasia syndrome type 2.

4. Hypersensitivity to liraglutide.

5. Previous treatment with liraglutide.

6. Known history of clinically significant gastroparesis.

10. For golimumab arm

1. Any history of recent (within 3 months) serious bacterial, viral, fungal, or
other opportunistic infections.

2. Any history of demyelinating diseases (such as multiple sclerosis), heart
failure, or left ventricular dysfunction.

3. Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.

4. Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB
infection.

5. Active infection with EBV, defined by any detectable viral DNA on real-time PCR
of plasma.

6. Active infection with CMV, defined by any detectable viral DNA on real-time PCR
of plasma.

7. Any of the following hematologic abnormalities:

- White blood count <3,000/μL or >14,000/μL

- Lymphocyte count <500/μL

- Platelet count <150,000 /μL

- Hemoglobin <8.5 g/dL

- Neutrophil count <2,000 cells/μL

8. Receipt of live vaccine (in the 6 weeks before treatment)