Effect of Dapagliflozin vs Sitagliptin on Liver Fat Accumulation and Body Composition in Patients With Diabetes Mellitus and Liver Transplantation: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Changes from baseline to month 12 in liver and pancreatic fat content.
研究概览
简要总结
Patients with pre-transplantation type 2 diabetes (T2D) and new-onset diabetes post liver transplantation (NODAT) are managed with multiple doses of subcutaneous insulin (MSI) following liver transplantation. As these patients receive oral glucocorticoids (mostly prednisolone) and immunosuppressants, which elevate blood glucose levels, multiple doses of insulin are usually required. After 2-3 months, when steroid doses are tapered and doses of immunosuppressants stabilize, insulin requirements subside and several oral hypoglycemic agents are initiated, such as metformin and sitagliptin. However, these agents are prescribed off-label as the data regarding the safety and efficacy of these agents in patients with liver transplantation are scarce.
Furthermore, several patients with liver transplantation develop fatty liver (liver steatosis) several months after transplantation, which is a risk factor for liver dysfunction. SGLT-2 inhibitors are reported to have favorable effect on liver fat accumulation in patients with T2D. However, the effect of SGLT-2 inhibitor on liver fat accumulation after liver transplantation has not been evaluated.
Chronic liver disease is associated with changes in body composition, especially increase in visceral fat and decrease in skeletal muscle mass. Data regarding the changes in body composition following liver transplantation are scarce.
In this RCT, Investigators aim to evaluate the effect of dapagliflozin vs sitagliptin on liver fat accumulation; body composition variables; and safety and efficacy of these oral hypoglycemic agents in patients with diabetes and liver transplantation
详细描述
To study the effect of dapagliflozin vs sitagliptin on liver fat accumulation in patients with diabetes and liver transplantation.
Material and Methods Ethical considerations The trial protocol is approved by the Medanta ethics committees. The trial will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. All the patients will be provided with written informed consent before participation.
Patients and study area A total of 100 patients will be enrolled for the study. Consecutive patients undergoing liver transplantation and attending outpatient Department of Endocrinology and Diabetes for management of diabetes mellitus will be enrolled. Diabetes mellitus will include both pre-transplantation type 2 diabetes as well as new-onset diabetes after transplantation (NODAT).
Statistical Analysis Plan:
The analysis will include profiling of patients on different demographic, clinical and laboratory parameters etc. Quantitative data will be presented in terms of means and standard deviation and qualitative/categorical data will be presented as absolute numbers and proportions. Cross tabulation will be generated and chi square test will be used for testing of association. Student t test will be used for comparison of quantitative outcome parameters and standard normal deviate test for proportions. P-value < 0.05 is considered statistically significant. SPSS software will be used for analysis.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of diabetes (pre-transplantation type 2 diabetes or new onset diabetes after transplantation)
- •Subjects taking insulin and/or metformin and/or sulfonylurea.
- •Body mass index (BMI) >=18.5 kg/m2
排除标准
- •Type 1 diabetes
- •Estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2, calculated by the Chronic Kidney Disease - Epidemiology (CKD-EPI) equation
- •Liver aminotransferases >3 times the upper limit of the reference range (upper normal limit AST or ALT >=40 units/L)
- •History of recurrent urinary tract infection
- •History or current acute or chronic pancreatitis
- •Presence of major contraindications to magnetic resonance imaging (cardiac pacemakers, claustrophobia, foreign bodies and implanted medical devices with ferromagnetic properties).
研究组 & 干预措施
Dapa Group
Patients with diabetes mellitus will receive dapagliflozin 10 mg once daily. Glycemic equipoise will be maintained between the two groups by adjusting insulin doses and/or metformin and/or sulfonylurea; maintaining target fasting glucose, post-prandial glucose and glycated hemoglobin (HbA1c) in accordance with the ADA 2021
干预措施: Dapagliflozin 10Mg Tab (Drug)
Sita Group
Patients with diabetes mellitus will receive sitagliptin 100 mg once daily.Glycemic equipoise will be maintained between the two groups by adjusting insulin doses and/or metformin and/or sulfonylurea; maintaining target fasting glucose, post-prandial glucose and glycated hemoglobin (HbA1c) in accordance with the ADA 2021
干预措施: Sitagliptin 100mg (Drug)
结局指标
主要结局
Changes from baseline to month 12 in liver and pancreatic fat content.
时间窗: 12 Month
MRI PDFF will be performed before and at 12 months
次要结局
- Changes in efficacy variables (proportion of individuals requiring insulin therapy at months 6 and 12, changes from baseline in HbA1c at months 6 and 12, and the percentage change from baseline in the total daily insulin dose at months 6 and 12).(12 Months)
- Safety assessment at months 3, 6, 9 and 12(12 Months)
- Change from baseline in body composition variables (body weight, BMI, body fat percentage, visceral adipose tissue, skeletal muscle mass and bone mineral content) at month 12. Body weight and BMI will be automatically recorded by the DEXA scan.(12 Months)
- Changes from baseline in liver aminotransferases (AST, ALT and GGT)(12 months)
研究者
Dr Mohammad Shafi Kuchay
Senior Consultant
Medanta, The Medicity, India