Effect of Sodium Glucose Co-transporter 2 Inhibitor on Inflammatory Cytokine in Type 2 Diabetes

Type2 Diabetes Mellitus Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02964572
• Other study ID #: 4-2016-0795
• Status: Completed
• Phase: N/A
• Start date: November 2016
• Est. completion date: July 2017

Study information

• Verified date: August 2020
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

• Single-center, prospective, active-controlled, open, randomized, 2 arm parallel, interventional, exploratory pilot

• Type 2 diabetic patients with high cardiovascular risks who have inadequate glycaemic control with metformin-based oral hypoglycemic agents will be prescribed glimepiride (comparison group) or empagliflozin (study group) for 60 days (plus or minus 32 days) as add-on therapy

• Changes in IL-1beta secretion, serum beta-hydroxybutyrate concentration, and NLRP3 inflammasome activity from baseline to final timepoint will be assessed.

Description:

First among cardiovascular (CV) end point trials of glucose-lowering agents, the EMPA-REG OUTCOME trial-using 10 or 25 mg/day SGLT2 inhibitor empagliflozin against placebo in 7,020 patients with T2DM who were at increased CV risk-reported a 14% reduction in major CV events and marked relative risk reductions in CV mortality (38%), hospitalization for heart failure (35%), and death from any cause (32%) over a median time period of 2.6 years. Though these results have raised the possibility that mechanisms other than those observed in the trial-modest improvement in glycemic control, small decrease in body weight, and persistent reductions in blood pressure and uric acid level-may be at play, it's not clearly known yet.

The inflammatory nature of atherosclerosis is well established. We hypothesized that empagliflozin might have an inhibitory effect on inflammasome activity in macrophages, thus contribute to cardioprotective effects in diabetes.

• Single-center, prospective, active-controlled, open, randomized, 2 arm parallel, interventional, exploratory pilot

• Type 2 diabetic patients with high cardiovascular risks who have inadequate glycaemic control with metformin-based oral hypoglycemic agents will be prescribed glimepiride (comparison group) or empagliflozin (study group) for 60 days (plus or minus 32 days) as add-on therapy

• Changes in IL-1beta secretion, serum beta-hydroxybutyrate concentration, and NLRP3 inflammasome activity from baseline to final timepoint will be assessed

• Healthy volunteers : effect of 3 day-ketogenic diet on changes in cytokines, metabolites (IL-1beta, beta-hydroxybutyrate , etc) and inflammasome activity in macrophages

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 85 Years

Eligibility

Inclusion Criteria:

• Age =19 years

• inadequate glycaemic control : HbA1c =6.5% or fasting glucose >120 mg/dl or random glucose >180 mg/dl

• High risk of cardiovascular events defined as the presence of =1 of the following:

1. History of myocardial infarction

2. Evidence of multi-vessel coronary artery disease

3. Evidence of single-vessel coronary artery disease with a positive non-invasive stress test for ischemia or history of hospitalization for unstable angina

4. History of stroke

5. Evidence of occlusive peripheral artery disease

6. Evidence of carotid atherosclerosis

7. Metabolic syndrome

• Healthy volunteers

Exclusion Criteria:

• Type 1 diabetes

• Organ transplantation

• Pregnant women

• eGFR <45

• Cortisol or growth hormone deficiency, pituitary diseases

• Gastric surgery

• Hematologic disorders

• Active cancers

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Intervention

Drug:
• Glimepiride
In accordance with the standard treatment guidelines of diabetes, glimepiride as a drug of active comparator will be administered to improve blood sugar in patients with poorly controlled blood sugar.
• Empagliflozin
Empagliflozin as a drug of experimental will be administered to improve blood sugar in patients with poorly controlled blood sugar.

Locations

Country	Name	City	State
Korea, Republic of	Yonsei University College of Medicine, Department of Internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	changes in the secretion of IL-1 beta from peripheral blood mononuclear cells	The effect of empagliflozin on the secretion of IL-1beta from peripheral blood mononuclear cells	Day 60
Secondary	Changes in the secretion of TNF-alpha from peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum concentrations of beta-hydroxybutyrate, before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in body weight (kg), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum concentrations of insulin (µU/mL), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum concentrations of glucagon (pg/mL), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum concentrations of free fatty acid (µEq/L), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum glycated albumin (%), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum concentrations of glucose (mg/dL), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum concentrations of uric acid (mg/dL), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum concentrations of liver enzymes (aspartate aminotransferase and alanine aminotransferase (IU/L)), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol (mg/dL)), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in serum concentrations of creatinine (mg/dL), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in spot urine concentrations of glucose (mg/dL) and creatinine (mg/dL) (those will be combined to report spot urine glucose-to-creatinine ratio in mg/mg), before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in mRNA expression level (PCR, fold) of IL-1beta, TNF-alpha, and NLRP3 in peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days
Secondary	Changes in protein expression pattern (western blot, relative to control) of IL-1beta, TNF-alpha, and NLRP3 in peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride		Day 60 plus or minus 32 days