Metformin Therapy for Overweight Adolescents With Type 1 Diabetes

Inclusion criteria

• 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.

• Age: 12 to <20 years.
• Duration of type 1 diabetes: ≥1 years.
• 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).
• Hemoglobin A1c: 7.5% - <10.0% from point of care measurement or local lab on day of screening visit or within 1 month prior.
• BMI: ≥85th percentile adjusted for age and sex .
• Total daily dose of insulin: ≥0.8 units per kg per day.
• 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.
• 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.
• Expected to comply with protocol in investigator's judgment.

Exclusion criteria

• 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).
• 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.
• 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.
• Any condition that in the judgment of the investigator will adversely affect the completion of the protocol.
• 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)
• Clinical diagnosis of celiac disease that is in poor control as defined by most recent tissue transglutaminase (tTG) that is in the abnormal range.
• History of ≥1 diabetic ketoacidosis events in the past 3 months.
• History of ≥1 severe hypoglycemic events (cognitive impairment that required assistance to treat) in the past 3 months.
• History of anemia or vitamin B12 deficiency in the past 2 years.
• Participation in an intervention study in the past 3 months.