Metformin Therapy for Overweight Adolescents With Type 1 Diabetes

Inclusion Criteria:

1. Clinical diagnosis of presumed autoimmune type 1 diabetes (T1D) as indicated by age of
diagnosis <10 years or documented positive diabetes-related autoantibodies.

a. Note: For randomization, presence of at least one of the diabetes-related
autoantibodies [Insulin autoantibodies (IAA) at diagnosis prior to initiation of
insulin, Islet cell antibodies (ICA), Anti-GAD (GAD65), Anti-IA2 (IA2), Zinc
Transporter 8 (ZnT8)] must be documented either from medical records or new laboratory
measurement (IAA and ICA not measured by central lab) sent to central lab for
participants who were ≥10 years old at diagnosis.

2. Age: 12 to <20 years.

3. Duration of type 1 diabetes: ≥1 years.

4. Current insulin regimen involves either use of an insulin pump or multiple daily
injections of insulin (at least 3 shots per day) for the last three months, with no
plans to switch the modality of insulin administration during the next 6 months (e.g.,
injection user switching to a pump, pump user switching to injections).

5. Hemoglobin A1c: 7.5% - <10.0% from point of care measurement or local lab on day of
screening visit or within 1 month prior.

6. BMI: ≥85th percentile adjusted for age and sex .

7. Total daily dose of insulin: ≥0.8 units per kg per day.

8. Average of ≥3 Self-Monitoring Blood Glucose (SMBG) tests per day prior to initiating
study and from download of study-provided blood glucose meter following screening
visit.

9. Available for at least 6 months of follow-up, has home phone (or access to phone), and
willing to be contacted by clinical site staff.

10. Expected to comply with protocol in investigator's judgment.

Exclusion Criteria:

1. Use of non-insulin medications for blood glucose control within prior 6 months or
planning to use within next 6 months (other than study drug).

2. Use of medications for weight reduction (such as: Belviq (lorcaserin), Qsymia
(Phentermine + topiramate), Orlistat (xenical)) within the prior 6 months or planning
to use within next 6 months.

3. Use of a medication such as stimulants, psychotropic agents and oral/inhaled
glucocorticoids that could affect weight gain or glycemic control of T1D or planning
to use within the next 6 months.

4. Any condition that in the judgment of the investigator will adversely affect the
completion of the protocol.

5. Females: pregnant, lactating, or intending to become pregnant within the next 34 weeks

- A negative urine pregnancy test will be required for all females An effective
contraceptive method or abstinence will be required for all females who have
experienced menarche

- Requirements regarding pregnancy testing prior to enrollment and monitoring for
pregnancy over the course of the study may be further defined by each individual
Institutional Review Board (IRB)

6. Clinical diagnosis of celiac disease that is in poor control as defined by most recent
tissue transglutaminase (tTG) that is in the abnormal range.

7. History of ≥1 diabetic ketoacidosis events in the past 3 months.

8. History of ≥1 severe hypoglycemic events (cognitive impairment that required
assistance to treat) in the past 3 months.

9. History of anemia or vitamin B12 deficiency in the past 2 years.

10. Participation in an intervention study in the past 3 months.