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

Phase 4

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: Placebo; Drug: Linagliptin

• Registration Number: NCT02372630
• Lead Sponsor: University at Buffalo

Brief Summary

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.

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 Timeline

• Study Start: 2014-05-23
• Study First Submitted: 2015-02-20
• Study First Submitted QC: 2015-02-25
• Study First Posted: 2015-02-26
• Primary Completion: 2018-02-01
• Study Completion: 2018-05-01
• Results First Submitted: 2022-02-22
• Status Verified: 2023-01
• Results First Submitted QC: 2023-01-24
• Last Update Submitted: 2023-01-24
• Results First Posted: 2023-02-21
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients will be treated for 12 weeks with placebo once daily
Linagliptin 5mg per day	Linagliptin	Patients will be treated for 12 weeks with Linagliptin 5mg once daily.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Oxidative Stress (as ROS Generation Level)	Week 0, Week 2, Week 4, Week 12	oxidative stress (ROS generation level) following linagliptin. ROS generation measurement by chemiluminescence of PMN cells
IL-1β mRNA Levels	Week 0, Week 2, Week 4, Week 12	Comparing IL-1B between Linagliptin group and placebo group based on the PCR test, between week 0 and week 12.
Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp	At baseline and week 12	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

Trial Locations

Locations (1)

ECMC Ambulatory Center, 3rd Floor; 🇺🇸 Buffalo, New York, United States