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
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
Detailed Description
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
Sample size: 200 Assuming that 40% people had HbA1c <7 in Dapagliflozin and 25% in sitagliptin.Alpha = 5%,Power = 80%,Need to enroll total 200 cases(100 in each arm), Drop rate = 10%,Total enrollment = 100 cases (80 each arm).
Randomization by block randomization method taking block size as 10 Intervention: This RCT will be conducted at ILBS New Delhi
Monitoring and assessment: Monitoring will be done for all the parameters of the objective. Documentation will be done for any adverse effects which will happen.
Adverse effects: to be monitored
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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% |
Drug: Metformin
Metformin: 1.5g/d CTPA,1g/d CTPB
Drug: Sitagliptin
Sitagliptin: Assess HbA1c/HBSG at 8 weeks, increase sitagliptin to 100 mg if HbA1c>7%
|
| Experimental: 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% |
Drug: Metformin
Metformin: 1.5g/d CTPA,1g/d CTPB
Drug: Dapagliflozin
Assess HbA1c/HBSG at 8 weeks, increase Dapagliflozin to 10 mg if HbA1c>7%
|
Outcome Measures
Primary Outcome Measures
- Percentage of patients with glycemic control at 24 weeks (HBA1c <7.0 %) [24 weeks]
Secondary Outcome Measures
- Percentage of patients with glycemic control at 8 and 16 weeks (HBA1c <7.0 %) [8 and 16 weeks]
- Ideal body weight loss of ≥3% relative to baseline at 24 week [24 weeks]
- Incidence and frequency of hypoglycemia (BS <54 mg/dl) episodes [8 weeks]
- Incidence and frequency of hypoglycemia (BS <54 mg/dl) episodes [16 weeks]
- Incidence and frequency of hypoglycemia (BS <54 mg/dl) episodes [24 weeks]
- Changes in HbA1c at 24 week relative to baseline [24 weeks]
- Changes in BMI at 24 week relative to baseline [24 weeks]
- changes in Blood insulin at 24 week [24 weeks]
- changes in lipid profile at 24 week [24 weeks]
- Change in ALT at 8, 16 and 24 week [8, 16 and 24 week]
- Change in HVPG at 24 week compared to baseline [24 weeks]
- Change in LSM at 24 week compared to baseline [24 weeks]
- Change in SSM at 24 week compared to baseline [24 weeks]
- Incidence of urinary protein excretion and serum creatinine at 8, 16 and 24 weeks [8, 16 and 24 weeks]
- Complications of cirrhosis (ascites, HE, Bleed, AKI, Infection) at 24 week [24 weeks]
- Medicine adherence rate in both groups [24 weeks]
- Adverse effects to study drugs in both groups [24 weeks]
- Mortality/ Liver transplantation in both groups [24 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18-70 years
-
Child A/B Liver cirrhosis in outpatient setting
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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
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HbA1c level of 7.1% or higher but no more than 9.0%
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BMI of 23 kg/m2 or higher
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patients who can be monitored closely for medication compliance
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patients who provide written informed consent.
Exclusion Criteria:
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Age <18 years
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Post renal or liver transplantation
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CTP C / ACLF
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Intrinsic/structural kidney disease, obstructive uropathy, ADPKD, Anatomic urologic defects that predispose to urinary tract infection
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Active sepsis / SBP at enrollment
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Grade II/III/IV HE
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Pregnancy or Lactating mother
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Known CKD, obstructive uropathy
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Patient on MV, NIV, systemic sepsis and shock
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Lack of informed consent
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Prior intolerance or S/E to SGLT-2i or DPP4i
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patients with type 1 diabetes or secondary diabetes
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patients with medical history of diabetic ketoacidosis
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patients with medical history of myocardial infarction, cerebral infarction, or stroke within 12 weeks before consent to the study
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estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m2
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unstable hypertension or dyslipidemia within 12 weeks before consent to the study
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HB <9 g/L, patients with haemoglobinopathy, acute hemolysisStudy period: one year after ethical approval.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dr Rakesh Kumar Jagdish | New Delhi | Delhi | India | 110070 |
Sponsors and Collaborators
- Institute of Liver and Biliary Sciences, India
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ILBS-Cirrhosis-68