The Impact Of Sodium-Glucose Cotransporter 2 Inhibitors on Metabolic Dysfunction -Associated Steatotic Liver Disease In Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 150
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
Study question 1:Could SGLT2-I improve hepatic fibrosis, steatosis, and inflammatory markers in type 2 diabetic patients with Metabolic associated steatotic liver disease Question 2:Which drug of SGLT2-I group is more effective in improving metabolic associated steatotic liver disease in type 2 diabetic patients?
详细描述
patients will be derived from Endocrine or Hepatology outpatient clinic and who were primarily visiting for management of type 2 diabetes and other comorbidities.
The effect of the SGLT2-I on metabolic associated steatotic liver disease patients with Type two diabetes mellitus will be a prospective, open-label, parallel-groups, randomized clinical study to examine the effect of different types of SGLT2-I (dapagliflozin, empagliflozin,) when included in the standard treatment of Type two diabetes mellitus versus standard treatment without SGLT2-I for 24 weeks based on a predefined computer-generated number with a 1:1 allocation that will be concealed in patients with Type 2 diabetes mellitus and Metabolic associated steatotic liver disease Patients will be treated with combination therapy metformin and/or sulfonylurea and/or dipeptidyl peptidase 4 (DPP-4) inhibitors and/or insulin (control group), for whom treatment with SGLT2-I plus standard treatment for type 2 diabetes. (SGLT2-I group) will be indicated due to poor diabetes control
- The patients will subsequently be classified and treated by the lines of diabetes therapy (based on randomization into SGLT2-I or control group).
Baseline assessment (First visit)
All patients before randomization will be subjected to :
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
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women aged ≥20 years old who will be:
- •Diagnosed with type 2 diabetes since ≥6 months in accordance with World Health Organization criteria (22); and
- •Present with glycated hemoglobin equal to or greater than 7% and less than 10% after at least three months of treatment with metformin monotherapy at the maximal tolerated dosage or sulfonylurea alone or in combination; and
- •Diagnosed with Metabolic associated steatotic liver disease
排除标准
- •Diagnosis or signs of type 1 diabetes or non-diabetic patients
- •Highly uncontrolled diabetes (HbA1c >86 mmol/mol [>10.0%])
- •BMI ≥40 kg/m2
- •Other causes of chronic hepatic steatosis (e.g., Hepatitis B virus ,Hepatitis c virus, autoimmune disease, Wilson disease, drugs, alpha one antitrypsin deficiency).
- •Patients use of drugs known to cause hepatic steatosis (e.g., amiodarone, valproate, tamoxifen, methotrexate, steroids)
- •Treatment with glucose-lowering drugs that influence liver fat, including thiazolidinediones, α-glucosidase inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors or any glucagon-like peptide-1 receptor agonists during the previous 3 months.
- •Detection of biliary duct obstruction based on imaging studies.
- •Patients with diagnosis of or clinical features that are suspected for another systemic disease that commonly causes liver disease.
- •Patient with history of liver transplantation
- •Evidence of cirrhosis (on basis of ultrasonography and MRI) or hepatocellular carcinoma (evidence on triphasic CT or MRI).
- •Positive HIV test
- •Treatment with vitamin E during the previous 3 months.
- •Intolerance or allergy SGLT2-I or any other substance in the tablets.
- •Contraindications to SGLT2-I use (history of acute or chronic pancreatitis or pancreatic cancer, or history of recurrent urinary tract or genital infections, current or previous gangrene).
- •History of or presence of (as found at Visit 1) any clinically significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study.
- •Creatinine clearance <90 ml/min at screening (Cockcroft-Gault formula).
- •Severe hepatic injury and/or significant abnormal liver function defined as aspartate aminotransferase >5× upper limit of normal (ULN) and/or alanine aminotransferase >5× ULN.
- •Total bilirubin >2.0 mg/dl (34.2 μmol/l)\
- •History of bariatric surgery or ongoing weight-loss diet (hypocaloric diet) or use of weight-loss agents unless the diet or treatment has been stopped at least 3 months before screening and that the patient has had a stable body weight (+/- 3 kg) during the 3 months before screening.
- •Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis results as judged by the investigator. This includes signs of liver disease other than non-alcoholic fatty liver disease that motivated further investigations or treatment based on clinical judgment.
- •Drug abuse or alcohol abuse.
- •Women who are pregnant, lactating or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since last menstrual period. Acceptable contraceptive methods will be combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomized.
- •Any other condition the investigator believed would interfere with the patient's ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the patient at undue risk.
- •Any blood donation/blood loss >500 ml during the 3 months prior to Visit 1 or during the study.
- •Patients with active malignancy
- •Patients with established hemolytic disease
- •Refused to consent to this study.
- •The patient will be excluded from the study after the randomization if the second compound of combination therapy is inconsistent with the standard of medical care in diabetes -
- •Patient use of anti-inflammatory medications or corticosteroids during the observational period
- •Missing the follow up.
研究组 & 干预措施
Control group
Control group (stander treatment of Type two diabetes mellitus without SGLT2-I )
干预措施: SGLT2 inhibitor (Drug)
Group dapa
Dapa group: (stander treatment of type two diabetes mellitus plus Dapagliflozin)
干预措施: SGLT2 inhibitor (Drug)
Group empa
Group empagliflozin: stander treatment of type two diabetes mellitus plus empagliflozin
干预措施: SGLT2 inhibitor (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: 6 months
Number of participants with tight controlled diabetes melitus
时间窗: 6 months
Measurement of glycated hemoglobin, random blood sugar,fasting blood sugar
次要结局
- Number of participant with changing in inflammatory biomarkers(6 months)
- Number of participants with changing Liver and spleen size(6 months)
- Number of participants with changing in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography(6 months)
研究者
George Esmat Roshdy
Assistant lecturer at internal medicine department faculty of medicine sohag university
Sohag University