Effect of Dapagliflozin vs Sitagliptin on Liver Fat Accumulation and Body Composition in Patients With Diabetes Mellitus and Liver Transplantation

NCT05042505 | Completed DMC

• 1 other identifier: MMDapa-LiT01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diabetes Mellitus; Liver Transplant; Complications

Outcome Measures

Primary Outcomes (1)

• Changes from baseline to month 12 in liver and pancreatic fat content.

  MRI PDFF will be performed before and at 12 months

  12 Month

Secondary Outcomes (4)

• 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

• 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

Study Arms (2)

Dapa Group

ACTIVE COMPARATOR

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

Sita Group

ACTIVE COMPARATOR

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

Interventions

Dapagliflozin 10Mg Tab DRUG

Dapa group (n = 50): Patients with diabetes mellitus will receive Dapagliflozin 10 mg

Dapa Group

Sitagliptin 100mg DRUG

Sita group (n = 50): Patients with diabetes mellitus will receive sitagliptin 100 mg once daily

Sita Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Pregnancy
• Presence of major contraindications to magnetic resonance imaging (cardiac pacemakers, claustrophobia, foreign bodies and implanted medical devices with ferromagnetic properties).

Sponsors & Collaborators

• Medanta, The Medicity, India: lead

Study Sites (1)

Division Of Endocrinology & Diabetes, Medanta The Medicity

Gurgaon, Haryana, 122001, India

Location

Related Publications (10)

• Ferrannini E, Seman L, Seewaldt-Becker E, Hantel S, Pinnetti S, Woerle HJ. A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes. Diabetes Obes Metab. 2013 Aug;15(8):721-8. doi: 10.1111/dom.12081. Epub 2013 Mar 4.

  PMID: 23398530 RESULT

• Kuchay MS, Farooqui KJ, Mishra SK, Mithal A. Glucose Lowering Efficacy and Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitors. Adv Exp Med Biol. 2021;1307:213-230. doi: 10.1007/5584_2020_479.

  PMID: 32006266 RESULT

• Rosenstock J, Seman LJ, Jelaska A, Hantel S, Pinnetti S, Hach T, Woerle HJ. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab. 2013 Dec;15(12):1154-60. doi: 10.1111/dom.12185. Epub 2013 Aug 22.

  PMID: 23906374 RESULT

• Kuchay MS, Krishan S, Mishra SK, Farooqui KJ, Singh MK, Wasir JS, Bansal B, Kaur P, Jevalikar G, Gill HK, Choudhary NS, Mithal A. Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial). Diabetes Care. 2018 Aug;41(8):1801-1808. doi: 10.2337/dc18-0165. Epub 2018 Jun 12.

  PMID: 29895557 RESULT

• Reeder SB, Sirlin CB. Quantification of liver fat with magnetic resonance imaging. Magn Reson Imaging Clin N Am. 2010 Aug;18(3):337-57, ix. doi: 10.1016/j.mric.2010.08.013.

  PMID: 21094444 RESULT

• Reeder SB, Cruite I, Hamilton G, Sirlin CB. Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy. J Magn Reson Imaging. 2011 Oct;34(4):729-749. doi: 10.1002/jmri.22775. Epub 2011 Sep 16.

  PMID: 22025886 RESULT

• Permutt Z, Le TA, Peterson MR, Seki E, Brenner DA, Sirlin C, Loomba R. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther. 2012 Jul;36(1):22-9. doi: 10.1111/j.1365-2036.2012.05121.x. Epub 2012 May 3.

  PMID: 22554256 RESULT

• Le TA, Chen J, Changchien C, Peterson MR, Kono Y, Patton H, Cohen BL, Brenner D, Sirlin C, Loomba R; San Diego Integrated NAFLD Research Consortium (SINC). Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: a randomized controlled trial. Hepatology. 2012 Sep;56(3):922-32. doi: 10.1002/hep.25731. Epub 2012 Jul 2.

  PMID: 22431131 RESULT

• Kuchay MS, Krishan S, Mishra SK, Choudhary NS, Singh MK, Wasir JS, Kaur P, Gill HK, Bano T, Farooqui KJ, Mithal A. Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial). Diabetologia. 2020 Nov;63(11):2434-2445. doi: 10.1007/s00125-020-05265-7. Epub 2020 Aug 31.

  PMID: 32865597 RESULT

• Krishan S, Jain D, Bathina Y, Kale A, Saraf N, Saigal S, Choudhary N, Baijal SS, Soin A. Non-invasive quantification of hepatic steatosis in living, related liver donors using dual-echo Dixon imaging and single-voxel proton spectroscopy. Clin Radiol. 2016 Jan;71(1):58-63. doi: 10.1016/j.crad.2015.10.002. Epub 2015 Nov 7.

  PMID: 26555703 RESULT

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

dapagliflozin; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Model Details: 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.

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 13, 2021
• Study Start: January 1, 2022
• Primary Completion: December 5, 2024
• Study Completion: February 27, 2026
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

IN (1)