The Association of Sodium-Glucose Cotransporter 2 Inhibitors Therapy With Elastographic and Molecular Markers of Liver Injury in Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Change in liver fibrosis (kPa)
研究概览
简要总结
Metabolic dysfunction-associated steatotic liver disease (MASLD), a condition where fat builds up in the liver, is common in patients with type 2 diabetes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors may help improve liver health, but their effects on liver stiffness and fat are not yet well understood. This study aims to clarify these effects.
Therefore, the aims of this study are:
- Measurement of liver stiffness and liver steatosis using novel ultrasound-based methods before initiating SGLT2 inhibitor therapy and 6 months after starting therapy.
- Assessment of blood biomarkers that may indicate liver injury, increased fat accumulation, and cellular dysfunction before initiating SGLT2 inhibitor therapy and 6 months after starting therapy.
- Evaluation of the relationship between biomarkers and ultrasound findings before the introduction of SGLT2 inhibitors and 6 months after the start of therapy.
详细描述
Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among patients with type 2 diabetes mellitus (T2DM), yet targeted therapeutic strategies remain limited. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated favorable metabolic and potential hepatoprotective effects, however, their impact on liver stiffness and steatosis has not been fully characterized.
This study was conducted to assess the effects of SGLT2 inhibitor therapy on non-invasive elastographic parameters and markers of liver injury in patients with T2DM. Liver stiffness was assessed using two-dimensional shear wave elastography (2D-SWE) and liver steatosis using ultrasound-guided attenuation parameter (UGAP), at baseline and after 6 months of treatment.
Comprehensive biochemical analysis was performed, including glucose, HbA1c, hematologic parameters, and standard liver function markers (AST, ALT, GGT, ALP, coagulation profile, albumin, total proteins, total and conjugated bilirubin, and lipid profile). Additionally, serum concentrations of key regulators of lipogenesis: Sterol Regulatory Element-Binding Protein 1 (SREBP1), Peroxisome Proliferator-Activated Receptor alpha (PPAR-α), Peroxisome Proliferator-Activated Receptor gamma (PPAR-γ), and Microsomal Triglyceride Transfer Protein (MTTP), were assessed at both time points.
The analysis aims to determine whether SGLT2 inhibitor therapy is associated with measurable improvements in liver stiffness, steatosis, and molecular markers of hepatic metabolic dysfunction, as well as to explore correlations between elastographic findings and circulating biomarkers. The results are expected to inform future research on the utility of these markers for diagnosing and monitoring MASLD and to support the potential expansion of therapeutic indications for SGLT2 inhibitors.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent, information for the participants and questionnaire
- •Patients that are 18 years of age or older
- •Diagnosis of type 2 diabetes mellitus
- •Patients being treated with an SGLT2 inhibitor for the first time
- •Patients who have been on stable antihyperglycemic therapy for 90 days (3 months) before enrollment in the study
排除标准
- •Patients taking drugs that are extremely hepatotoxic, i.e., require additional monitoring of liver function during therapy (e.g., chemotherapeutic agents, biological therapy)
- •Patients taking drugs which cause drug-induced fatty liver disease (DIFLD): amiodarone, tamoxifen, methotrexate, 5-Fluorouracil, irinotecan, l-asparaginase, valproate, tetracycline, nucleoside reverse transcriptase inhibitors (NRTIs such as lamivudine, tenofovir, zidovudine etc.)
- •Patients with liver cancer, hemochromatosis, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), hepatitis C virus (HCV), hepatitis B virus (HBV), liver cirrhosis or autoimmune hepatitis.
- •Patients who are alcohol addicted, i.e., consume more than two alcoholic beverages per day (for women) or more than three alcoholic beverages per day (for men)
- •Mentally ill patients who are incapable of making their own independent decisions and have a legal custodian
- •Pregnant women and nursing mothers
- •Patients who are on insulin therapy
结局指标
主要结局
Change in liver fibrosis (kPa)
时间窗: Baseline, after 6 months
Liver fibrosis is assessed using the two-dimensional shear wave elastography (2D-SWE)
Change in liver steatosis (dB/cm/MHz)
时间窗: Baseline, after 6 months
Liver steatosis is assessed using the ultrasound-guided attenuation parameter (UGAP).
Change in glucose levels (mmol/L)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in HbA1c (%)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in HbA1c (mmol/mol)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in enzyme activity (U/L) of AST, ALT, GGT, ALP
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in Prothrombin Time ratio and change in activated Partial Thromboplastin Time ratio
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in Prothrombin Time-INR
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in Thrombin Time (s) and change in activated Partial Thromboplastin Time (s)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in concentration (g/L) of albumins and total proteins
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in concentration (µmol/L) of total bilirubin and conjugated bilirubin
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in Hematocrit ratio (L/L)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in fibrinogen activity (g/L)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in concentration (mmol/L) of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in Hemoglobin concentration (g/L)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in concentration (ng/L) of SREBP-1, PPAR alpha, PPAR gamma and MTTP
时间窗: Baseline, after 6 months
Assessment via ELISA
Change in in White Blood Cell (WBC) Count (x 10^9/L) and Platelet Count (x 10^9/L)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
Change in Red Blood Cell (RBC) Count (x 10^12/L)
时间窗: Baseline, after 6 months
Assessment via biochemical analyses
次要结局
- Questionnaire on lifestyle and dietary habits(Baseline, after 6 months)
研究者
Farah Khaznadar
Principal Investigator
Josip Juraj Strossmayer University of Osijek