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

NCT ID: NCT02964572

Last Updated: 2020-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2017-07-31

Brief 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.

Detailed 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

Conditions

Type2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Glimepiride

Glimepiride (anti-diabetic drug) as a comparison group

Group Type: ACTIVE_COMPARATOR

Glimepiride

Intervention Type: DRUG

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 (anti-diabetic drug) as a study group

Group Type: EXPERIMENTAL

Empagliflozin

Intervention Type: DRUG

Empagliflozin as a drug of experimental will be administered to improve blood sugar in patients with poorly controlled blood sugar.

Interventions

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.

Intervention Type: DRUG

Empagliflozin

Empagliflozin as a drug of experimental will be administered to improve blood sugar in patients with poorly controlled blood sugar.

Intervention Type: DRUG

Other Intervention Names

Amaryl; Jardiance

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Yonsei University College of Medicine, Department of Internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes center

Seoul, , South Korea

Countries

South Korea

References

Kim ER, Kim SR, Cho W, Lee SG, Kim SH, Kim JH, Choi E, Kim JH, Yu JW, Lee BW, Kang ES, Cha BS, Lee MS, Cho JW, Jeon JY, Lee YH. Short Term Isocaloric Ketogenic Diet Modulates NLRP3 Inflammasome Via B-hydroxybutyrate and Fibroblast Growth Factor 21. Front Immunol. 2022 Apr 28;13:843520. doi: 10.3389/fimmu.2022.843520. eCollection 2022.

Reference Type: DERIVED

PMID: 35572519 (View on PubMed)

Other Identifiers

4-2016-0795

Identifier Type: -

Identifier Source: org_study_id