Effect of Dapagliflozin vs Sitagliptin on Liver Fat Accumulation and Body Composition in Patients With Diabetes Mellitus and Liver Transplantation (Dapa-LiT)

February 27, 2026 updated by: Dr Mohammad Shafi Kuchay, Medanta, The Medicity, India

Effect of Dapagliflozin vs Sitagliptin on Liver Fat Accumulation and Body Composition in Patients With Diabetes Mellitus and Liver Transplantation: a Randomized Controlled Trial

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Eligibility criteria Inclusion criteria

  1. Diagnosis of diabetes (pre-transplantation type 2 diabetes or new onset diabetes after transplantation)
  2. Subjects taking insulin and/or metformin and/or sulfonylurea for at least 3 months since liver transplantation
  3. Body mass index (BMI) more than or equal to 18.5 kg/m2

Exclusion criteria

  1. Type 1 diabetes
  2. Estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2, calculated by the Chronic Kidney Disease - Epidemiology (CKD-EPI) equation
  3. Liver aminotransferases >3 times the upper limit of the reference range (upper normal limit AST or ALT >=40 units/L)
  4. History of recurrent urinary tract infection
  5. History or current acute or chronic pancreatitis
  6. Pregnancy
  7. Presence of major contraindications to magnetic resonance imaging (cardiac pacemakers, claustrophobia, foreign bodies and implanted medical devices with ferromagnetic properties).

All patients will be randomized to one of the following intervention groups: Sita group (n = 50): patients with diabetes mellitus receiving multiple doses of insulin plus metformin 500 mg twice daily plus sitagliptin 100 mg once daily and Dapa group (n = 50): patients with diabetes mellitus receiving multiple doses of insulin plus metformin 500 mg daily plus dapagliflozin 10 mg once daily. Glycemic equipoise will be maintained between the two groups by adjusting insulin doses and maintaining target fasting glucose, post-prandial glucose and glycated hemoglobin (HbA1c) in accordance with the ADA 2021.

Imaging Liver fat content and pancreatic fat content will be assessed by magnetic resonance imaging (MRI) proton density fat Fraction (PDFF) at the beginning of study and again after 12 months of intervention. MRI-PDFF is a robust technique for noninvasive quantification of liver fat. Multiple human studies have shown that this method accurately estimates PDFF in the liver. This method has been shown to be both accurate, and reproducible. Investigators have validated this technique for Indian population and is already used in the E-LIFT and D-LIFT trials.

Body composition by Dual energy X-ray absorptiometry (DEXA) Body composition will be assessed by DEXA using the Hologic Horizon DXA System (USA) with Discovery software, version 12.3 (Bellingham, WA, USA). DEXA provides a rapid and non-invasive fat mass, fat free mass and bone mineral density. DEXA is considered to be the reference method for body composition assessment in clinical research. The DEXA-measured body composition variables that will be included for analysis are weight (kg), body mass index (BMI), total fat mass (kg), android fat mass (g), gynoid fat mass (g), visceral adipose tissue (VAT) mass (g), VAT area (cm2), and abdominal subcutaneous adipose tissue (SAT) mass (g). Obesity will be defined as BMI >25 kg/m2 in accordance with World Health Organization (WHO) Asia pacific guidelines. The skeletal muscle mass index (SMI) will be the appendicular skeletal muscle divided by the height in meters squared. Low appendicular skeletal mass index will be defined as <7.0 kg/m2 for men and <5.4 kg/m2 for women, as per Consensus Report of the Asian Working Group for Sarcopenia (AWGS).

Bioelectrical impedance (BIA) analysis Multi-frequency bioelectrical impedance analysis was completed using InBody 570 body composition analyzer (Biospace, Inc. Seoul, Korea). The InBody 570 is a multi-frequency analyzer and divides the body into five components: two arms, two legs, and a trunk. The electrodes are situated beneath the subject's feet on the platform and on the palms and thumbs attached to handles on the device. Age, height and gender are manually entered after weight is determined by a scale positioned within device.

Laboratory workup Biochemical parameters will include fasting plasma glucose, glycosylated hemoglobin (HbA1C), lipid profile, hemogram, kidney function test (urea, creatinine) and liver function test (total and fractionated bilirubin, alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total protein, albumin) before and after the intervention period.

End points and safety assessments The primary endpoint will be changes from baseline in MRI-PDFF assessed liver and pancreatic fat content at month 12. The secondary outcome measures will be changes from baseline in liver aminotransferases (AST, ALT and GGT) at month 12. Changes from baseline in body composition variables (weight, BMI, body fat percentage, visceral adipose tissue, skeletal muscle mass and bone mineral content) at month 12. Efficacy variables will include 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 (by collecting the daily record of the last week at months 6 and 12). Safety assessment will include adverse events (AEs), serious AEs (SAEs), physical examination findings, vital signs and laboratory values. AEs of special interest will be genital infections, urinary tract infections, volume depletion, fractures, worsening renal function, hepatobiliary AEs, hypersensitivity, and cardiovascular AEs.

Study outcomes The primary outcome measures are

1. Changes from baseline to month 12 in liver and pancreatic fat content. The secondary outcome measures are

  1. 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
  2. Changes from baseline in liver aminotransferases (AST, ALT and GGT)
  3. 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).
  4. Safety assessment at months 3, 6, 9 and 12 (as described above).

Table 2. Safety summary Characteristic

>=1 AEs >=1 AEs related to the study drug AE leading to study discontinuation AEs of special interest Genital infection Urinary tract infection Renal impairment Fractures Hypotension/dehydration/hypovolemia Hypersensitivity Cardiovascular events SAEs >=1 SAEs >=1 SAEs related to the study drug SAEs leading to study discontinuation Death

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Haryana
      • Gurgaon, Haryana, India, 122001
        • Division Of Endocrinology & Diabetes, Medanta The Medicity

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosis of diabetes (pre-transplantation type 2 diabetes or new onset diabetes after transplantation)
  2. Subjects taking insulin and/or metformin and/or sulfonylurea.
  3. Body mass index (BMI) >=18.5 kg/m2

Exclusion Criteria:

  1. Type 1 diabetes
  2. Estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2, calculated by the Chronic Kidney Disease - Epidemiology (CKD-EPI) equation
  3. Liver aminotransferases >3 times the upper limit of the reference range (upper normal limit AST or ALT >=40 units/L)
  4. History of recurrent urinary tract infection
  5. History or current acute or chronic pancreatitis
  6. Pregnancy
  7. Presence of major contraindications to magnetic resonance imaging (cardiac pacemakers, claustrophobia, foreign bodies and implanted medical devices with ferromagnetic properties).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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
Drug: Dapagliflozin 10Mg Tab
Dapa group (n = 50): Patients with diabetes mellitus will receive Dapagliflozin 10 mg
Active Comparator: 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
Drug: Sitagliptin 100mg
Sita group (n = 50): Patients with diabetes mellitus will receive sitagliptin 100 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes from baseline to month 12 in liver and pancreatic fat content.
Time Frame: 12 Month
MRI PDFF will be performed before and at 12 months
12 Month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 12 Months
DEXA will be performed before and at 12 months
12 Months
Changes from baseline in liver aminotransferases (AST, ALT and GGT)
Time Frame: 12 months
Liver enzymes will be performed before, 6 months and at 12 months
12 months
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).
Time Frame: 12 Months
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) will be recorded in detail.
12 Months
Safety assessment at months 3, 6, 9 and 12
Time Frame: 12 Months
Safety parameters will be recorded before ,6 months and at 12 months
12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medanta, The Medicity, India

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2022

Primary Completion (Actual)

December 5, 2024

Study Completion (Actual)

February 27, 2026

Study Registration Dates

First Submitted

August 27, 2021

First Submitted That Met QC Criteria

September 6, 2021

First Posted (Actual)

September 13, 2021

Study Record Updates

Last Update Posted (Actual)

March 3, 2026

Last Update Submitted That Met QC Criteria

February 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MMDapa-LiT01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be shared after a reasonable request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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