Metformin Therapy for Overweight Adolescents With Type 1 Diabetes
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Overweight
Intervention: Metformin (glucophage); oral placebo
Intervention description: The strength of each tablet will be 500 mg. Participants will build up to a daily dose over four weeks by taking one tablet per day for 7 days, one tablet twice daily for 7 days, one tablet in morning and 2 tablets at night for 7 days, and then 2 tablets in the morning and 2 tablets at night, daily throughout the remainder of the study treatment period.
Intervention MeSH terms: Metformin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 164.0
Sex: All
Minimum age: 12 Years
Maximum age: 19 Years
Healthy volunteers: No

Summary:

      The objective of the proposed research is to evaluate the efficacy and safety of the use of
      metformin in addition to standard insulin therapy in overweight and obese children and
      adolescents, age 12-<20 years, with type 1 diabetes for at least 1 year. Secondary objectives
      are to assess the effect of metformin on C-peptide levels, a measure of how much insulin is
      still being produced by the beta cells of the pancreas, and on vascular dysfunction. In
      addition, an ancillary study is planned to assess if metformin will improve tissue-specific
      insulin resistance in type 1 diabetes using a hyperinsulinemic euglycemic clamp.
    

Eligibility criteria:

        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.