Effect of Gemigliptin on Metabolic Endotoxemia and Lipemia

Study Overview
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Brief Summary
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This is an exploratory study on the metabolic endotoxemia associated with type 2 diabetes. The investigators will measure systemic endotoxin level and lipid level after ingestion of high fat diet to evaluate the effect of gemigliptin, a DPP-4 inhibitor, on metabolic endotoxemia and lipemia induced by high fat diet.

Detailed Description
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Study subjects will be allocated to either gemigliptin or placebo. After 4 weeks of treatment and 2 weeks of wash out period, all subjects will be switched to the opposite arm. The subjects will be tested oral fat tolerance test and adipose tissue needle biopsy(only for the subjects who agreed to participate donate adipose tissue) at 3 time points: the start of 1st treatment, end of 1st treatment and end of 2nd treatment.

Official Title
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Evaluation of the Effect of Gemigliptin on Metabolic Endotoxemia and Lipemia Induced by High Fat Diet in Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Gemigliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 20 to 75 At least 6 months from the diagnosis of type 2 diabetes Current diabetes treatment: life style modification and/or metformin and/or sulfornylurea No change of the diabetes treatment (drug number and dossage) in recent 3 months HbA1c 6.5% to 10% Exclusion Criteria: Recent cardiovascular event in 6 months Concurrent use of statin or fibrate or ezetimibe Renal failure, chronic liver disease Pregnancy or lactation Use of other DPP-4 inhibitor or GLP-1 analogue in recent 3 months

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemigliptin<br>Gemigliptin 50mg qd added to subjects current diabetes treatment | Drug: Gemigliptin<br> <br> * Other names: Zemiglo;|
| Placebo Comparator: Placebo<br>Placebo (identical in appearance to gemigliptin) | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between baseline and peak serum LPS | The increment of serum LPS after ingestion of high fat diet | serum LPS before high fat diet and 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr after high fat diet | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting serum LPS level | Compare fasting LPS level between treatment group | After 10 hrs of fasting | 
| Incremental AUC of serum LPS during oral fat tolerance test | Calculated incremental AUC of serum LPS | serum LPS before high fat diet and 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr after high fat diet | 
| Difference between baseline and peak serum triglyceride level | The increment of serum TG after ingestion of high fat diet | serum TG before high fat diet and 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr after high fat diet | 
| Incremental AUC of serum triglyceride level during oral fat tolerance test | Calculated incremental AUC of serum TG | serum TG before high fat diet and 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr after high fat diet | 
| Difference between baseline and peak serum apolipoprotein-B48 | The increment of serum apolipoprotein-B48 after ingestion of high fat diet | serum apolipoprotein-B48 before high fat diet and 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr after high fat diet | 
| Incremental AUC of serum apolipoprotein-B48 during oral fat tolerance test | Calculated incremental AUC of serum apolipoprotein-B48 | serum apolipoprotein-B48 before high fat diet and 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr after high fat diet | 
| Serum level of inflammatory markers (CRP, TNF-alpha, IL-6) | Compare serum level of inflammatory markers between treatment groups | After 10 hr of fasting | 
| mRNA expression level of inflammatory markers in the adipose tissue | Compare mRNA expression level of inflammatory markers | After high fat diet ingestion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes mellitus, metabolic endotoxemia, gemigliptin, DPP-4 inhibitor