Fatty Liver Study in Patients With Type II Diabetes

Study Overview
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Brief Summary
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The primary objective of this trial is to measure changes in hepatic lipid content using three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.

Detailed Description
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In patients with type 2 diabetes whose glycemic control is not accomplished with Metformin alone, there are several options for additional hypoglycemic agent. As per recent National guidelines at least three second line agents can be added to metformin: thiazolidinediones, Lantus insulin, and DPP4 inhibitors. All three approaches have been proven to help accomplishing goals of therapy for glycemic control (HbA1c<7%) in clinical trials. Whether one approach is superior to the other in improving associated non-glycemic metabolic abnormalities and risk for future morbidity and mortality in patients with type 2 diabetes remains a matter of intense debate. Among these abnormalities, excessive triglyceride content in the liver (fatty liver or liver steatosis) is a major predictor of risk for non-alcoholic steato-hepatitis (NASH) and liver cirrhosis. Fatty liver is highly prevalent in patients with type 2 diabetes. There are no clinical studies done to determine if any of these three therapeutic options is superior at reducing the liver triglyceride content in patients with type 2 diabetes and fatty Liver. Therefore, in this study we propose to measure and compare the effects on liver triglyceride content when either pioglitazone, lantus insulin, or DPP4 inhibitors are added to metformin in patients with poorly controlled type 2 diabetes (HbA1c>7.6%) and fatty liver (presence of bright liver in abdominal ultrasound). The primary objective of this trial is to measure changes in hepatic lipid content using three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.

Official Title
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A Phase IV, Open Label, Randomized Trial on the Effect of Metformin Plus Lantus Insulin, Pioglitazone, or DPP4 Inhibitor on Fatty Liver in Patients With Type II Diabetes

Conditions
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Type II Diabetes, Nonalcoholic Fatty Liver

Intervention / Treatment
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* Drug: DPP4 inhibitor
* Drug: Pioglitazone
* Drug: Lantus insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided informed consent in a manner approved by the Institutional Review Board (IRB) and is willing and able to comply with the trial procedures. Adults at least 18 years of age at the time of consent. Have type 2 diabetes mellitus. Be on a stable medication with metformin (2000 mg/day) for at least 3 months prior to study enrollment. Have blood A1c >7.6% and < 8.5% within 3 months prior to study enrollment. Have fatty liver, which is diagnosed by ultrasonographic findings of bright liver within 1 year of study enrollment. Stable medication for lipid lowering, blood pressure control, dietary supplements, including vitamins, for at least 3 months. Women of Childbearing Potential must be willing and able to use acceptable forms of birth control while on the study. Exclusion Criteria: Currently taking medication that can affect glucose metabolism other than Metformin. History of Kidney diseases that, in the opinion of the investigator , would place the subject at increased risk of participation or plasma levels of creatinine > 1.4 for women and > 1.5 for men. History of Cirrhosis of liver, hepatitis, or other liver diseases that, in the opinion of the investigator, would place the subject at increased risk of participation. Current alcohol consumption more than12 to 15 g of alcohol a day, or >12 oz of beer, 5 oz of wine, or 1.5 oz of distilled spirits. History of heart failure. Concurrent participation on another research study Use of an investigational agent in the 30 days prior to signing informed consent. History of prior non-compliance or the presence or history of psychiatric conditions (including drug or alcohol addiction) that would, in the opinion of the investigator, make it difficult for the subject to comply with the study procedures or follow the investigators instructions. Females who are pregnant or lactating Current Diagnosis or History of Bladder Cancer

Ages Eligible for Study
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Minimum 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: Thiazolidinedione<br>(Pioglitazone, 15 mg/day) | Drug: Pioglitazone<br>* Comparison between three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.<br>* Other names: Pioglitazone 15 mg daily;|
| Active Comparator: Lantus Insulin<br>0.35 U per kg body weight once daily | Drug: Lantus insulin<br>* Comparison between three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.<br>* Other names: Lantus insulin (0.35U/kg of body weight once daily);|
| Active Comparator: DPP4 inhibitor<br>Sitagliptin, 100 mg/day or Saxagliptin, 5 mg/day | Drug: DPP4 inhibitor<br>* Comparison between three common alternative therapeutic strategies to improve glycemic control in patients with type 2 diabetes who are not controlled with metformin alone.<br>* Other names: saxagliptin 5 mg daily;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hepatic Lipid Content From Baseline Visit to Six Month Follow up Visit | Comparison of the hepatic lipid content measurement taken by MRI at baseline with the measurement taken by MRI at the 6 month follow up visit. | Hepatic lipid content measurement will be taken on Day #1 ( the day of randomization) and at the 6 month follow up visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type II Diabetes, Nonalcoholic fatty liver