Metformin Induces a Dietary Restriction-like State in Human

Study Overview
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Brief Summary
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The fact that metformin treatment has been associated with reduced risk of cancer and cardiovascular disease raises the possibility of a beneficial role of metformin for other age-related diseases. The actions of metformin resemble the effects of calorie restriction (CR) to some extent, and microarray analyses have shown that metformin induces a gene expression profile that aligns with that of CR in animal. The aim of the study is to investigate whether metformin treatment can induce dietary restriction-like state in human. Sixty overweight subjects will be included in this study, and participants will be divided 3 groups (20 cases in each group)including metformin group (0.85, twice daily), standard diet group, and CR group. All subjects will be treated 6 months. At the end of this study, blood samples and muscle samples will be obtained.

Detailed Description
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Blood samples will be obtained from all individuals. blood lipids, inflammation markers, insulin, glucose, leptin,adiponectin, ala aminotransferase, asp aminotransferase, creatine phosphokinase,lactate dehydrogenase, alkaline phosphatase,bilirubin, cyclo-oxygenase, citrate synthase, renal function, leukocyte telomere length ratio, and telomerase activity will be measured before and after the treatments.Also, hyperinsulinemic-euglycemic clamp will be performed before and after the treatments. Muscle samples will be obtained by biopsy for 9 individuals (3 cases from each group) at the end of the study. Microarray analysis will be performed for the gene expression profile from the muscle samples. Other protein expressions such asadenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor coactivator 1a (PGC-1a) activity,will be checked by Western blot.

Official Title
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Chronic Metformin Treatment Induces a Dietary Restriction-like State in Overweight Human

Conditions
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Overweight Subjects, Metformin, Aging

Intervention / Treatment
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* Drug: metformin 0.85 twice daily for 6 months
* Behavioral: Calorie restriction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overweight Male Exclusion Criteria: Female Obesity Using any other drugs < 18 years old > 60 years old Mental disorders Surgery history for abdomen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: Metformin group<br>Metformin 0.85 twice daily for 6 months | Drug: metformin 0.85 twice daily for 6 months<br> <br> |
| No Intervention: Standard diet group<br> | |
| Other: CR group<br>Calorie restriction diet will be given to this group. | Behavioral: Calorie restriction<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The differences of gene expression profile among 3 groups. | The gene expression profile will be checked by microarray, and compared the number differences of pathways among 3 groups. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The differences of insulin sensitivity in 3 groups | The insulin sensitivity will be measured by insulin clamp assays, and be compared before and after 6 months as well as among 3 group at the end of this study. | 6 months |