The Effect of LINAGLIPTIN on Inflammation, Oxidative Stress and Insulin Resistance in Obese Type 2 Diabetes Subjects (1971)

The Effect of TRADJENTA ® (LINAGLIPTIN) on Inflammation, Oxidative Stress and Insulin Resistance in Obese Type 2 Diabetes Subjects

This is a single center, prospective randomized double blind, parallel and placebo controlled study to evaluate oxidative stress and inflammation before and after treatment with linagliptin for 12 weeks. We will also, testing whether Linagliptin is an insulin sensitizer.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Linagliptin

Detailed Description

This is a single center, prospective randomized double blind, parallel and placebo-controlled study to evaluate oxidative stress and inflammation before and after treatment with linagliptin for 12 weeks. The study enrolls type 2 patients with diabetes.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14215
      • ECMC Ambulatory Center, 3rd Floor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Age 20-80 years inclusive. Type 2 diabetes BMI ≥30 kg/m2 Subjects on statins, ACE inhibitors, thiazolidinediones and antioxidants will be allowed as long as they are on stable doses of these compounds and the dosage in not changed during the course of study.

HbA1c ≤ 8.0%

Exclusion Criteria:

- Use of GLP-1 agonists or DPP-IV therapy in the last 3 months. History of Pancreatitis. Risk for pancreatitis, i.e., history of gallstones, alcohol abuse, and hypertriglyceridemia.

Subjects who are taking antiplatelet or anticoagulant medications will be excluded from the fat biopsy portion of the study.

Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks Hepatic disease (liver function tests more than 3 times the upper limit of normal) Renal impairment (serum eGFR <30 ml/min) Any other life-threatening, non-cardiac disease Uncontrolled hypertension (BP > 160/100 mm of Hg) Congestive Heart Failure class III or IV. Use of an investigational agent or therapeutic regimen within 30 days of study Participation in any other concurrent clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients will be treated for 12 weeks with placebo once daily	Drug: Placebo; matching placebo giving orally daily
Active Comparator: Linagliptin 5mg per day; Patients will be treated for 12 weeks with Linagliptin 5mg once daily.	Drug: Linagliptin; 5 mg daily oral tablets of linagliptin; Other Names: TRADJENTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
JNK-1 Protein in MNC	JNK-1 protein in MNC before and after linagliptin use as compared to placebo.	Week 0, Week 2, Week 4, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-1β mRNA Levels	Comparing IL-1B between Linagliptin group and placebo group based on the PCR test, between week 0 and week 12.	Week 0, Week 2, Week 4, Week 12
Oxidative Stress (as ROS Generation Level)	oxidative stress (ROS generation level) following linagliptin. ROS generation measurement by chemiluminescence of PMN cells	Week 0, Week 2, Week 4, Week 12
Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp	Insulin sensitivity is measured with HE clamp. Glucose Infusion Rate was titrated to maintain blood glucose concentration at the fasting glucose level. Plasma samples for glucose was obtained at 10-minute intervals starting 30 minutes before the clamp, to quantitate rates of whole-body glucose disposal. Difference from baseline at 12 weeks is calculated and compared to placebo arm	At baseline and week 12

Collaborators and Investigators

• Sponsor: University at Buffalo
• Collaborators: Kaleida Health

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2014
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: February 20, 2015
• First Submitted That Met QC Criteria: February 25, 2015
• First Posted (Estimate): February 26, 2015

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin
• Other Study ID Numbers: 514091