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

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.

Study Overview

• Status: Withdrawn
• Conditions: Diabetes; SGLT-2 Inhibitors; Advanced Glycation End Products
• Intervention / Treatment: Drug: empagliflozin; Drug: linagliptin

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwell Health

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2017
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 9, 2016
• First Posted (Estimate): May 11, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2018
• Last Update Submitted That Met QC Criteria: February 13, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Empagliflozin; Linagliptin
• Other Study ID Numbers: SGLT2-AGE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No