Adjunctive Metformin Therapy in Double Diabetes
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Intervention: Metformin; Placebo
Intervention description: Metformin 1000 mg once daily by mouth for 9 months; 2 capsules once daily by mouth for 9 months
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: 28.0
Sex: All
Minimum age: 10 Years
Maximum age: 20 Years
Healthy volunteers: No
Keywords: Double Diabetes; Type 1 diabetes; Type 2 diabetes; Obesity; Acanthosis nigricans; Diabetes associated autoantibodies

Summary:

      The significance of this project is to investigate the effects of adjunctive metformin
      therapy in children and adolescents with double diabetes. Double diabetes describes a
      clinical state where an individual possesses features of both type 1 and type 2 diabetes.
      There is a paucity of data on the role of adjunctive metformin therapy in children and
      adolescents with double diabetes. To help fill this knowledge gap, the investigators propose
      a randomized, double-blind, placebo-controlled trial of metformin in double diabetes.
      Specifically, the investigators will evaluate changes in hemoglobin A1c and anthropometry in
      patients with a diagnosis of type 1 diabetes who also have features of type 2 diabetes or
      metabolic syndrome as well as patients with type 2 diabetes who possess diabetes-associated
      autoantibodies. This will help determine the safety profile, and efficacy of adjunctive
      metformin therapy in these subjects.
    

Eligibility criteria:

        Inclusion Criteria:

        A. General inclusion criteria

          1. Ten to 20 years of age.

          2. Pubertal (Tanner stages 2-5, by examination).

          3. Hemoglobin A1c level of > 8.0% in the 6 months prior to enrollment.

          4. All subjects must have access to a computer.

        B. Specific inclusion criteria: [Subjects could have either #1, or #2].

          1. Subjects with clinical and biochemical features of T2DM of > 6mo duration who also
             have positive T1DM antibodies

               -  Clinical features: acanthosis nigricans, BMI >85%

               -  Biochemical: evidence of insulin resistance at diagnosis

               -  fasting insulin >27 uIU/mL(normal range 6-27) at a fasting blood glucose of ≥ 126
                  mg/dL, or

               -  fasting c-peptide level of > 7.1 ng/mL (normal range 0.9 - 7.1), or

               -  Homeostasis model of insulin resistance of >3.16

          2. Patients with T1DM of > one yr duration with BMI >85%

               -  Presentation with ketoacidosis at diagnosis

               -  C-peptide <0.9 ng/mL (normal range 0.9 - 7.1),or (insulin < 6 uIU/mL) (NR 6-27)
                  at diagnosis (when blood glucose is ≥ 126 mg/dL)

               -  Can be antibody positive or negative

               -  Increased insulin requirement (>2 Units/kg/day)

        Exclusion Criteria:

          1. Subjects on weight altering medications, such as orlistat.

          2. Subjects with eating disorder

          3. Subjects on medications other than insulin and or metformin that may affect blood
             glucose level.

          4. Subjects with abnormal hepatic function tests.

          5. Subjects with nephropathy, defined in this case as an overnight albumin excretion rate
             of >200 mcg/min using a first morning urine sample collection.

          6. Subjects with recurrent diabetes ketoacidosis (more than 2 episodes in the past 12
             months), or recurrent severe hypoglycemia (more than 2 episodes of hypoglycemia with
             altered level of consciousness, requiring assistance to treat in the past year).

          7. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate
             contraceptive measures.

          8. Known or suspected allergy to metformin.

          9. The receipt of any investigational drug within 6 months prior to this trial.

         10. Active malignant neoplasms.

         11. No access to a computer.

         12. Subjects currently taking metformin for clinical purposes are not eligible to be
             enrolled in this study.