The Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Advanced Glycation End Products

Study Overview
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Brief Summary
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Single-center open-label multiple dose randomized two period cross-over study to examine Advanced Glycation End Product (AGE) levels in human subjects pre and post empagliflozin administration.

Detailed Description
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Single-center open-label multiple dose randomized two period cross-over study. The North-Shore Long Island Jewish Institutional Review Board will be used to approve our study protocol. All patients will give written informed consent and comply with the Helsinki agreement and good clinical practices guidelines. Treatment Plan: Eligible patients will be randomized to receive linagliptin 5mg daily or empagliflozin 25mg daily for 30 days followed by a 30 day washout period and crossover. All pre-existing diabetic medications will continue unchanged. Fasting blood carboxymethyl lysine (CML), methylglyoxal (MG), vascular cell adhesion molecule (VCAM), tumor necrosis factor (TNF) alpha, 8-isoprostane, and routine chemistries and urinary CML, MG, and creatinine will be measured at baseline, after 30 days, 60 days and 90 days. AGE levels will be measured by Elisa.

Official Title
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The Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Advanced Glycation End Products

Conditions
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SGLT-2 Inhibitors, Advanced Glycation End Products, Diabetes

Intervention / Treatment
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* Drug: empagliflozin
* Drug: linagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T2DM Age ≥ 18 glomerular filtration rate ≥ 30 ml/min/1.73 m2 body-surface area A1C ≥ 7% any higher limit SLGT-2 inhibitor naïve On stable doses of current medications for at least 3 months. Exclusion Criteria: Indication of liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 2 x upper limit of normal during screening or run-in phase Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells Contraindications to background therapy according to the local label Any uncontrolled endocrine disorder except type 2 diabetes Pre-menopausal women (last menstruation ≤1 year prior to informed consent) who were nursing, pregnant, or of child-bearing potential and were not practicing an acceptable method of birth control, or did not plan to continue using this method throughout the study, or did not agree to submit to periodic pregnancy testing during the trial o Acceptable methods of birth control include tubal ligation, transdermal patch, intrauterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence, double barrier method, vasectomy of partner Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another trial involving an investigational drug and/or follow-up

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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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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Linagliptin<br>Eligible patients were randomized to receive linagliptin 5mg daily for 30 days. | Drug: empagliflozin<br>* Test to see how 30 days of jardiance changes serum and urinary advanced glycation end product levels<br>* Other names: Jardiance;|
| Experimental: Empagliflozin<br>Eligible patients were randomized empagliflozin 25mg daily for 30 days. | Drug: linagliptin<br>* Test to see how 30 days of tradjenta changes serum and urinary advanced glycation end product levels<br>* Other names: tradjenta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AGE levels | Measurement of serum and urinary AGE levels | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure | measurement of BP | 30 days | 
| Change in weight | measurement of weight | 30 days |