A Pilot Study to Assess the Glucose Lowering Effect of Metformin and Sitagliptin in Adolescents With Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to see if the use of metformin and sitagliptin used in conjunction with insulin can improve the blood sugars of teenagers with Type 1 diabetes.

Detailed Description
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The study will include a total of 4 visits. The time period between the very first visit and the very last visit will be between 10 and 15 weeks. Each participant will be randomized to one of the 3 groups in the study. The groups are as follows: Group 1: Insulin and sitagliptin Group 2: Insulin and metformin Group 3: Insulin and combination of sitagliptin and metformin The study is a randomized open label design. All subjects will undergo a screening visit; if inclusion and exclusion criteria are fulfilled they will be enrolled in the study. At the time of enrollment the subject will continue their home insulin regimen and will be randomized to an add an oral hypoglycemic agent(s) : metformin, sitagliptin or combination therapy (metformin and sitagliptin). The total duration on study medication will be 6 weeks. All subjects will undergo a baseline mixed meal tolerance test (MMTT) in their standard or usual insulin Each subject will undergo a total of two studies. Blood draws will be necessary.

Official Title
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A Pilot Study to Assess the Glucose Lowering Effect of Metformin and Sitagliptin in Adolescents With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Metformin
* Drug: Sitagliptin + Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of 13 to 18 years HbA1c >7.5% but <10% Subjects must be on intensive insulin management Tanner stage greater than or equal to 4 Must have T1DM for at least one year , T1DM defined by ADA criteria and having at least one of the following antibodies: Anti-GAD, Anti-islet, Anti-insulin C-peptide > 0.6 ng/ml Exclusion Criteria: Type 2 diabetes History of any other chronic condition (except hypothyroidism stable on medications) Actively taking medications that may affect glucose excursions (steroids or oral contraceptives) Evidence of anemia, clinically significant elevation of the liver enzymes (3 X normal), amylase or lipase (2 X normal), abnormal triclycerides (3 X normal), abnormal renal function test An unsupportive family environment and pregnant or lactating females

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin plus sitagliptin<br>The subjects continued their usual insulin regimen throughout the study. Sitagliptin was started and continued at 50 mg orally twice daily | Drug: Sitagliptin<br>* up to 50 mg twice a day<br>* Other names: Januvia;|
| Active Comparator: Insulin plus metformin<br>The subjects continued their usual insulin regimen throughout the study. Metformin was started at 500 mg orally daily. The dose was increased over a 2 week period up to 2,000 mg per day as tolerated. | Drug: Metformin<br>* up to 1000 mg twice a day<br>* Other names: Glucophage;|
| Active Comparator: Insulin plus sitagliptin and metformin<br>The subjects continued their usual insulin regimen throughout the study. Sitagliptin was started and continued at 50 mg orally twice daily. Metformin was started at 500 mg orally daily. The dose was increased over a 2 week period up to 2,000 mg per day as tolerated. | Drug: Sitagliptin + Metformin<br>* up to 50/1000 mg twice a day<br>* Other names: Sitagliptin + Metformin = Janumet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the glucose lowering effect of metformin and sitagliptin alone and as combination therapy when used as adjuncts to insulin in adolescents with T1DM. | Glucose concentrations and AUC glucose calculation | 10 - 15 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescents