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

Yonsei University61 enrolled

Overview

* 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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Conditions

Type2 Diabetes Mellitus

Interventions

GlimepirideDRUG

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.

EmpagliflozinDRUG

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

Eligibility

Sex: ALLMin age: 19 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

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

Seoul, South Korea

Outcomes

Primary Outcomes

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

Time frame: Day 60

Secondary Outcomes

Changes in the secretion of TNF-alpha from peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride