Effect of Sodium-glucose Cotransporter-2 Inhibitor in Cellular Senescence in Patients With Cardiovascular Diseases or Type 2 Diabetes
- Conditions
- Sodium-Glucose Transporter 2 InhibitorsDiabetes MellitusCellular Senescence
- Interventions
- Drug: SGLT2 inhibitor
- Registration Number
- NCT05975528
- Lead Sponsor
- Yonsei University
- Brief Summary
Patients with type 2 diabetes (T2D) are more prevalent with aging-related comorbidities and frailty, which leads to a shorter life expectancy than non-diabetic individuals and that this excess mortality is largely attributable to cardiovascular causes.
Therefore, since diabetes accelerates cellular senescence, attenuating aging process in patients with T2D is expected to reduce progression of comorbidities and eventually increase lifespan.
According to previous studies, sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown increased ketone bodies not only in blood but in various tissues including liver, kidney and colon, which could lead to beneficial effects in metabolic diseases. Especially, β-hydroxybutyrate (βHB) inhibits oxidative stress and reduces insulin resistance, which has a positive effect on preventing cardio-renal-metabolic diseases and aging process in patients with T2D.
In this context, SGLT2 inhibitor can be a promising option to alleviate senescence process in patients with T2D. However, despite the accumulating evidence that support anti-senescent effect of SGLT2 inhibitor in preclinical models, no clinical study has investigated association between SGLT2 inhibitor use and senescence patients with T2D.
Thus, the objective of this study is to determine whether the use of SGLT2 inhibitor is associated with anti-senescent effect in patients with T2D, which may expand the indications of SGLT2 inhibitor other than glycemic control.
- Detailed Description
\<Study design\>
* Prospective study : Patients with type 2 diabetes who started antidiabetics for the first time or were taking antidiabetics (metformin-based monotherapy or 2- or 3- agent therapy), requiring additional glycemic control by either SGLT2 inhibitor and non-SGLT2 inhibitor(sulfonylurea) are enrolled in this study.
* Drug administration period: Total 180 days, but non-SGLT2 inhibitor administration period is 3 months, and then changed to the SGLT2 inhibitor another 3 months. Health people are also recruited for comparison with patients with T2D.
* Drug administration: For the SGLT2 inhibitor group, empagliflozin 10mg or dapagliflozin 10mg once daily is administered. For the non-SGLT2 inhibitor group (minimum glimepiride 1mg) was administered depending of the patient's glycemic status and hypoglycemic risk.
* Glimepiride and gliclazide, both belonging to the sulfonylurea class, can be administered interchangeably.
* Additionally, medication dosages may be adjusted based on blood glucose and test results, and DPP4 inhibitors may be added according to medical judgment, following the guidelines of the Korean Diabetes Association.
\< Study methods\>
1. After explaining the contents of the study and obtaining consent during hospitalization or outpatient visit, 20ml of additional whole blood is additionally obtained when blood is collected for routine medical purpose. Also, for those agreed to participate in the study, albuminuria and proteinuria are measured and the remaining specimens (5ml) are stored.
2. Among all patients participating in the study, blood and urine samples should be collected to measure the following parameters in each visit (1\~3): fasting glucose, fasting insulin, fasting c-peptide, HbA1c, beta-hydroxybutyrate, free fatty acid-fasting, postprandial 90 min glucose/insulin/c-peptide, BUN, creatinine, eGFR, AST, ALT, ALP, GGT, total bilirubin, total protein, albumin, uric acid, total cholesterol, triglyceride, HDL, LDL, WBC, hemoglobin, hematocrit, platelet, c-reactive protein, urinalysis with microscopy. In addition, the following tests including liver fibroscan (Incorporation of fibroscan conducted up to 3 months before/after registration for reference and use during registration) and body composition tests are conducted to check for diabetic complications.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 92
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Glimepiride user Glimepiride - SGLT2 inhibitor user SGLT2 inhibitor -
- Primary Outcome Measures
Name Time Method Changes of Cellular senescence markers Changes from baseline to 3 months after use of SGLT2 inhibitors Changes of cellular senescence markers (CD57+CD28- T cell, CD87+ monocyte) between SGLT2 inhibitor users and glimepiride users
- Secondary Outcome Measures
Name Time Method Changes of Senescence-associated secretory phenotype Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors SASP (Senescence-associated secretory phenotype) : IL-1/6, TNFa, MCP-1
Changes of body composition using Inbody (kg) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors Changes of body composition using Inbody: Skeletal muscle mass (kg) Body fat mass (kg) Right arm muscle mass (kg) Left arm muscle mass (kg) Trunk muscle mass (kg) Right leg muscle mass (kg) Left leg muscle mass (kg)
Changes of biochemistry profiles in blood (g/dL) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood Hemoglobin (g/dL)
Changes of biochemistry profiles in blood (mg/dL) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood Creatinine (mg/dL), Total cholesterol (mg/dL), Triglyceride (mg/dL), HDL-cholesterol (mg/dL), Fasting glucose (mg/dL)
Changes of biochemistry profiles in blood (IU/L) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood AST (IU/L), ALT (IU/L), γ-Glutamyl transferase (IU/L)
Changes of biochemistry profiles in blood (μU/mL) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood Fasting Insulin (μU/mL)
Changes of body composition using Inbody (cm2) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors Changes of body composition using Inbody: Visceral fat area (cm2)
Changes of biochemistry profiles in blood (mg/L) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood C-Reactive Protein(mg/L)
Changes of biochemistry profiles in blood (μEq/L) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood Free fatty acid-Fasting (μEq/L)
Changes of biochemistry profiles in blood (10^3/μL) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood WBC count (10\^3/μL), Platelet counts (10\^3/μL)
Changes of biochemistry profiles in blood (%) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood Hematocrit (%), HbA1c (%)
Changes of biochemistry profiles in blood (mmol/L) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors - Changes in Biochemistry profiles in blood Beta-hydroxybutyrate (mmol/L)
Changes of body composition using Inbody (cm) Changes from baseline to 3 months/6 months after use of SGLT2 inhibitors Changes of body composition using Inbody: Weight circumference (cm) Hip circumference (cm)
Trial Locations
- Locations (1)
Yonsei University College of Medicine
🇰🇷Seoul, Korea, Republic of