Insulin Clamp Ancillary Study for Assessment of Insulin Resistance

Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (T1D)--Insulin Clamp Ancillary Study for Assessment of Insulin Resistance

Insulin Clamp Ancillary study for Assessment of Insulin Resistance will be conducted as a sub-study to the main protocol, Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (NCT01881828). The purpose of this ancillary study is to assess if metformin will improve tissue-specific insulin resistance (IR) in type 1 diabetes using a hyperinsulinemic euglycemic clamp; a 3-month randomized trial comparing metformin versus placebo in 12 to <20 year olds with BMI >85th percentile ( total daily insulin dose >0.7 units/kg, and HbA1c 7.0%-9.9%).

A central pharmacy will compound a placebo to match the metformin tablets. The placebo product will contain the following components: Micosolle™, silica based excipient Silicified Micro Crystalline Cellulose, National Formulary Safflower Oil, United States Pharmacopeia K-30 Povidone Powder Magnesium Stearate, National Formulary (Vegetable source) Fumed Silica, National Formulary

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 the 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.

Hyperinsulinemic euglycemic clamp to assess metformin's impact on muscle IR via glucose infusion rate (GIR).

Graded hyperinsulinemic euglycemic clamp with glucose and glycerol isotopes to assess metformin's impact on: • Hepatic IR

Graded hyperinsulinemic euglycemic clamp with glucose and glycerol isotopes to assess metformin's impact on: • Adipose IR

Inclusion Criteria: 1. Meets eligibility criteria of the main study, Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (NCT01881828). Exclusion Criteria: 1. Low hemoglobin or hematocrit as defined by each local institution's rules for insulin clamps or if no institutional requirements a Hematocrit <30% or hemoglobin <10 gm/dL

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