An Open Label Randomized Control Trial to Compare the Safety and Efficacy of Dapagliflozin Plus Metformin Versus Sitagliptin Plus Metformin for Treatment of Diabetes in Patients With Compensated and Stable Decompensated Cirrhosis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Percentage of patients with glycemic control at 24 weeks (HBA1c <7.0 %)
研究概览
简要总结
Diabetes prevalence is increasing among cirrhotics and use of OAD in cirrhotics is limited because of risk of hypoglycaemia and other adverse effects, therefore in this study we would be using OAD in the form of Sitagliptin or Dapagliflozin to look for glycemic response as well as to look for other benefits such as weight reduction and improvement in lipid parameters.
详细描述
Hypothesis In patients with cirrhosis and T2DM with poor glycemic control on metformin requiring dual therapy, Dapagliflozin is safe and superior to Sitagliptin in achieving glycemic control. Moreover, Dapagliflozin use leads to improvement in parameters of metabolic dysfunction, clinical decompensation and cardio-renal protection.
Aim compare the safety and efficacy of metformin plus sitagliptin compared to metformin plus dapagliflozin in effective glycemic control and improvement in parameters of metabolic dysfunction, cirrhosis complications and organ dysfunction at 24 weeks.
Study population:Patients with compensated and stable decompensated cirrhosis and age 18-70 years with CTP 5-8
Study design: A prospective, randomized, single center open label study
The study will be conducted on the consecutive patients with liver cirrhosis and type 2 diabetes mellitus seen at the outpatient clinics of Department of Hepatology, ILBS
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-70 years
- •Child A/B Liver cirrhosis in outpatient setting
- •T2DM patients who have not used any glucose-lowering agents within 8 weeks before consenting, or those who have only used metformin, in addition to diet and exercise
- •HbA1c level of 7.1% or higher but no more than 9.0%
- •BMI of 23 kg/m2 or higher
- •patients who can be monitored closely for medication compliance
- •patients who provide written informed consent.
排除标准
- •Age <18 years
- •Post renal or liver transplantation
- •CTP C / ACLF
- •Intrinsic/structural kidney disease, obstructive uropathy, ADPKD, Anatomic urologic defects that predispose to urinary tract infection
- •Active sepsis / SBP at enrollment
- •Grade II/III/IV HE
- •Pregnancy or Lactating mother
- •Known CKD, obstructive uropathy
- •Patient on MV, NIV, systemic sepsis and shock
- •Lack of informed consent
- •Prior intolerance or S/E to SGLT-2i or DPP4i
- •patients with type 1 diabetes or secondary diabetes
- •patients with medical history of diabetic ketoacidosis
- •patients with medical history of myocardial infarction, cerebral infarction, or stroke within 12 weeks before consent to the study
- •estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m2
- •unstable hypertension or dyslipidemia within 12 weeks before consent to the study
- •HB <9 g/L, patients with haemoglobinopathy, acute hemolysisStudy period: one year after ethical approval.
研究组 & 干预措施
Metformin with Dapagliflozin
Metformin: 1.5g/d CTPA,1g/d CTPB
Dapagliflozin: Assess HbA1c/HBSG at 8 weeks, increase dapagliflozin to 10 mg if HbA1c>7%
干预措施: Dapagliflozin (Drug)
Metformin with Sitagliptin
Metformin: 1.5g/d CTPA,1g/d CTPB Sitagliptin: Assess HbA1c/HBSG at 8 weeks, increase sitagliptin to 100 mg if HbA1c>7%
干预措施: Metformin (Drug)
Metformin with Sitagliptin
Metformin: 1.5g/d CTPA,1g/d CTPB Sitagliptin: Assess HbA1c/HBSG at 8 weeks, increase sitagliptin to 100 mg if HbA1c>7%
干预措施: Sitagliptin (Drug)
Metformin with Dapagliflozin
Metformin: 1.5g/d CTPA,1g/d CTPB
Dapagliflozin: Assess HbA1c/HBSG at 8 weeks, increase dapagliflozin to 10 mg if HbA1c>7%
干预措施: Metformin (Drug)
结局指标
主要结局
Percentage of patients with glycemic control at 24 weeks (HBA1c <7.0 %)
时间窗: 24 weeks
次要结局
- Change in LSM at 24 week compared to baseline(24 weeks)
- Ideal body weight loss of ≥3% relative to baseline at 24 week(24 weeks)
- changes in Blood insulin at 24 week(24 weeks)
- Incidence and frequency of hypoglycemia (BS <54 mg/dl) episodes(24 weeks)
- Percentage of patients with glycemic control at 8 and 16 weeks (HBA1c <7.0 %)(8 and 16 weeks)
- Changes in BMI at 24 week relative to baseline(24 weeks)
- changes in lipid profile at 24 week(24 weeks)
- Number of patients with Complications of cirrhosis (ascites, HE, Bleed, AKI, Infection) at 24 week(24 weeks)
- Changes in HbA1c at 24 week relative to baseline(24 weeks)
- Change in ALT at 8, 16 and 24 week(8, 16 and 24 week)
- Medicine adherence rate in both groups(24 weeks)
- Incidence of urinary protein excretion at 8, 16 and 24 weeks(8, 16 and 24 weeks)
- Change in HVPG at 24 week compared to baseline(24 weeks)
- Change in SSM at 24 week compared to baseline(24 weeks)
- Incidence of serum creatinine at 8, 16 and 24 weeks(8, 16 and 24 weeks)
- Adverse effects to study drugs in both groups(24 weeks)
- Number of patients with Mortality/ Liver transplantation in both groups(24 weeks)