The Role of CYP8B1 Polymorphisms in Modulating the Biochemical Pathways Affected by SGLT2 Inhibitors in T2DM and Obesity
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Change in Body Weight (kg) from Baseline to 6 Months
研究概览
简要总结
This study explores the long-term effects of dapagliflozin and empagliflozin on CYP8B1 gene expression and a range of metabolic, oxidative, and inflammatory biomarkers in obese patients with Type 2 Diabetes Mellitus (T2DM). Over a 6-month period, participants are assigned to three treatment arms: metformin (control), dapagliflozin, and empagliflozin. The study aims to determine how these medications influence bile acid metabolism, oxidative stress, leptin, GLP-1, IL-10, and IFN-γ, providing insight into the broader metabolic benefits of SGLT2 inhibitors
详细描述
Detailed Description Type 2 Diabetes Mellitus (T2DM) and obesity are major global health burdens with shared pathophysiological mechanisms, including insulin resistance, chronic inflammation, and altered lipid metabolism. SGLT2 inhibitors, such as empagliflozin and dapagliflozin, have emerged as effective glucose-lowering agents that also offer additional benefits, including weight reduction, cardiovascular protection, and renal function preservation.
Despite these advantages, the therapeutic response to SGLT2 inhibitors is variable, often influenced by individual genetic differences. A key genetic determinant is CYP8B1 (cytochrome P450 family 8 subfamily B member 1), a gene encoding sterol 12-alpha-hydroxylase, which regulates bile acid synthesis and lipid metabolism. Polymorphisms in CYP8B1 may impact drug metabolism and alter bile acid-mediated metabolic regulation, potentially affecting both the efficacy and safety profile of SGLT2 inhibitors.
This clinical trial aims to investigate the role of CYP8B1 genetic variations in modifying the clinical and biochemical responses to empagliflozin and dapagliflozin therapy among obese patients recently diagnosed with T2DM.
Participants will be randomized into three groups:
- Group 1: Empagliflozin 10 mg daily
- Group 2: Dapagliflozin 10 mg daily
- Group 3 (Control): Standard care (lifestyle modification and/or metformin)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed with Type 2 Diabetes Mellitus (within the past 6 months).
- •Body Mass Index (BMI) ≥ 30 kg/m² (classified as obese).
- •No prior treatment with SGLT2 inhibitors or other antidiabetic medications.
- •Willing and able to provide written informed consent.
- •Able to comply with study visits, procedures, and sample collection.
排除标准
- •History or diagnosis of Type 1 diabetes mellitus or secondary forms of diabetes.
- •Estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73 m² (moderate to severe renal impairment).
- •Active liver disease or significant hepatic dysfunction.
- •Current pregnancy or breastfeeding.
- •Known hypersensitivity or contraindication to SGLT2 inhibitors.
- •hypertension
- •Any other condition that, in the opinion of the investigator, may interfere with the patient's ability to complete the study or pose additional risk.
研究组 & 干预措施
Empagliflozin Group
Participants in this group will receive empagliflozin 10 mg orally once daily for a duration of 6 months. The intervention aims to evaluate the effect of empagliflozin on weight reduction, metabolic parameters, and biochemical outcomes in newly diagnosed obese T2DM patients, with a focus on the influence of CYP8B1 polymorphisms on treatment response.
干预措施: Empagliflozin (oral) (Drug)
Dapagliflozin Group
Participants in this group will receive dapagliflozin 10 mg orally once daily for a duration of 6 months. This arm is designed to assess the clinical and biochemical effects of dapagliflozin, particularly regarding changes in adipokines, lipid profile, insulin sensitivity, and the impact of CYP8B1 genetic variations.
干预措施: Dapagliflozin (DAPA) (Drug)
Control Group
Participants in this group will receive standard care, including dietary and lifestyle modifications and metformin therapy if clinically indicated, according to ADA guidelines. This arm will serve as a comparator to evaluate the relative efficacy of SGLT2 inhibitors and the role of CYP8B1 polymorphisms in treatment outcomes.
干预措施: Metfomin (Drug)
结局指标
主要结局
Change in Body Weight (kg) from Baseline to 6 Months
时间窗: Baseline and 6 months
Body weight will be measured using a calibrated digital scale at baseline and at 6 months. The change in weight will be calculated by subtracting baseline weight from 6-month weight.
Change in Serum Total Cholesterol (mg/dL) from Baseline to 6 Months
时间窗: Baseline to 6 Months
Serum total cholesterol will be measured using standard enzymatic methods at baseline and after 6 months. The change will be calculated by subtracting baseline values from follow-up values.
Change in Malondialdehyde (MDA) Levels (µmol/L) from Baseline to 6 Months
时间窗: Baseline to 6 Months
Serum MDA will be measured using the TBARS assay to assess lipid peroxidation and oxidative stress.
CYP8B1 Gene Expression Changes
时间窗: Baseline to 6 Months
Measure CYP8B1 mRNA expression using real-time PCR to evaluate the relationship between gene expression and treatment response.
次要结局
- Change in Adiponectin Levels(Baseline to 6 Months)
- Change in HbA1c(Baseline to 6 Months)
- Change in Fasting Blood Glucose(Baseline to 6 Months)
- Change in C-Peptide Levels(Baseline to 6 Months)
- Change in Blood Ketone Body Levels(Baseline to 6 Months)
- Change in Serum HDL Cholesterol (mg/dL) from Baseline to 6 Months(Baseline and 6 Months)
- change in Serum LDL Cholesterol (mg/dL) from Baseline to 6 Months(Baseline and 6 Months)
- Change in Serum Triglycerides (mg/dL) from Baseline to 6 Months(Baseline and 6 Months)
- Change in Superoxide Dismutase (SOD) Activity (U/mL) from Baseline to 6 Months(Baseline and 6 Months)
- Change in Serum Interleukin-10 (IL-10) Levels (pg/mL) from Baseline to 6 Months(Baseline to 6 Months)
- Change in Glutathione Peroxidase (GPx) Activity (U/mL) from Baseline to 6 Months.(Baseline to 6 Months)
- Change in Catalase Activity (U/mL) from Baseline to 6 Months(Baseline to 6 Months)
- Change in Interferon-Gamma (IFN-γ) Levels (pg/mL) from Baseline to 6 Months(Baseline to 6 Months)
- Change in Nitric Oxide (NO) Levels (µmol/L) from Baseline to 6 Months(Baseline and 6 Months)
研究者
Ahmed Abdulrazzaq Bapir
PhD Student (under supervision of Prof. goran othman )
Kurdistan Higher Council of Medical Specialties