Effect of Dulaglutide on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

NCT03590626 | Completed DMC

• 1 other identifier: MMDLIFT01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This D-LIFT (Effect of dulaglutide on Liver Fat) trial is an investigator initiated, prospective, open label, randomized clinical study to examine the effect of dulaglutide 0.75 mg subcutaneously weekly for 4 weeks, followed by 1.5 mg weekly for 20 weeks when included in the standard treatment for type 2 diabetes vs. standard treatment for type 2 diabetes (minus dulaglutide) in patients with type 2 diabetes and NAFLD. Hepatic steatosis (intracellular fat accumulation in hepatocytes) will be measured by MRI-PDFF, a validated quantitative biomarker for liver fat. The study will be conducted according to the CONSORT guidelines. The patient population for the trial will be derived from Medanta-The Medicity Hospital endocrine out-patient clinic, who would primarily visit for management of type 2 diabetes and other co-morbidities. The study will be conducted in Medanta-The Medicity Hospital, Gurugram, Haryana, which is a tertiary care center in North India. Patients deemed eligible will be screened for the trial. The clinical trial protocol will be presented for approval to the institutional ethics review board. Informed written consent will be obtained from all the participants before enrolment into the study.

Conditions

Non Alcoholic Fatty Liver Disease; Type2 Diabetes Mellitus

Keywords

Non Alcoholic Fatty Liver Disease; Type 2 Diabetes Mellitus; GLP-1 receptor agonist; Dulaglutide; MRI-Proton density fat fraction; Fat Mapping; Non Alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Change in liver fat

  change in liver fat quantified by MRI-PDFF in colocalized regions of interest (ROI) within each of the nine liver segments

  Baseline to 24 weeks

Secondary Outcomes (6)

• Change in Biochemical Markers

  Basline to 24 weeks

• Change in Fibroscan Parameters

  Basline to 24 weeks

• Change in Fibroscan Parameters

  Basline to 24 weeks

• change in cardiometabolic markers

  Basline to 24 weeks

• Change in Biochemical Markers

  Baseline to 24 weeks

Study Arms (2)

Dulaglutide group

EXPERIMENTAL

receive dulaglutide 0.75 mg weekly for 4 weeks followed by 1.5 mg weekly for 20 weeks plus standard treatment for type 2 diabetes

Drug: Dulaglutide

Control group

NO INTERVENTION

receive standard treatment for type 2 diabetes and up titration of treatment will be done by anti-diabetic medicines other than the GLP-1 receptor agonist

Interventions

Dulaglutide DRUG

0.75 mg weekly for 4 weeks followed by 1.5 mg weekly for 20 weeks

Dulaglutide group

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A man or woman, 20 years of age or above with the diagnosis of type 2 diabetes for at least 3 months who meets all of the following two criteria:
• On standard anti-diabetic agents (metformin, DPP-4 inhibitors, sulphonylureas or insulin, in any combination) with an HbA1c of ≤ 7.0% and ≥10.0% (≤53 and ≥86 mmol/mol) at screening
• Have documented hepatic steatosis (MRI-PDFF \>6%) on screening MRI-PDFF
• Subjects must be medically stable on the basis of medical history, physical examination and laboratory investigations.
• Subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
• Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of the study and are willing to participate in the study

You may not qualify if:

• History of diabetic ketoacidosis, type 1 diabetes, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy.
• History of brittle or labile glycemic control, with widely varying glucose measurements by FPG or SMBG such that stable glucose control over the treatment period would be unlikely.
• History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 3 years before Screening, or an Alcohol Use Disorders Identification Test (AUDIT) with a score ≥8, or alcohol consumption of more than 20 g per day in the case of women and more than 30 g per day in the case of men for at least three consecutive months during the previous 5 years.
• Thyroid stimulating hormone (TSH) value that is either \< 0.45 mIU/L or \>10 mIU/L at Screening.
• Note: Subjects on thyroid hormone replacement therapy must be on a stable dose and dosing regimen for at least 4 weeks prior to enrollment.
• Use of a PPARγ agonist \[e.g., a thiazolidinedione (pioglitazone\], an SGLT2 inhibitor (e.g., canagliflozin, empagliflozin) or another GLP-1 receptor agonist (e.g., liraglutide) within 24 weeks before the enrollment.
• BMI ≥23 kg/m2 or ≤40 kg/m2.
• Ongoing eating disorder, or a significant weight loss or weight gain within 12 weeks before the Screening visit, defined as an increase or decrease of 5% in body weight based upon clinic-based measurement or, if not available, based on subject's report.
• Use of weight loss medication (prescription and/or over-the-counter) within 3 months prior to Screening or have participated in a weight loss/diet program within 12 months prior to Screening.
• Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant.
• Myocardial infarction, unstable angina, pulmonary hypertension, revascularisation procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 3 months before Screening, or revascularisation procedure is planned, or subject has a history of New York Heart Association (NYHA) Class III-IV cardiac disease.
• History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
• Use of vitamin E within 3 months before screening.
• History of prior bariatric (e.g., Roux-en-Y gastric bypass) or other major upper gastrointestinal surgical procedure (including gastric resection).
• History of diabetic gastroparesis (or symptoms suggestive of this disorder, including postprandial bloating or vomiting), malabsorption, inflammatory bowel disease, or any other chronic, clinically important gastrointestinal disorder.

Sponsors & Collaborators

• Medanta, The Medicity, India: lead

Study Sites (1)

Division Of Endocrinology & Diabetes, Medanta The Medicity

Gurgaon, Haryana, 122001, India

Location

Related Publications (12)

• Umpierrez G, Tofe Povedano S, Perez Manghi F, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care. 2014 Aug;37(8):2168-76. doi: 10.2337/dc13-2759. Epub 2014 May 19.

  PMID: 24842985 BACKGROUND

• Bouchi R, Nakano Y, Fukuda T, Takeuchi T, Murakami M, Minami I, Izumiyama H, Hashimoto K, Yoshimoto T, Ogawa Y. Reduction of visceral fat by liraglutide is associated with ameliorations of hepatic steatosis, albuminuria, and micro-inflammation in type 2 diabetic patients with insulin treatment: a randomized control trial. Endocr J. 2017 Mar 31;64(3):269-281. doi: 10.1507/endocrj.EJ16-0449. Epub 2016 Dec 3.

  PMID: 27916783 RESULT

• Petit JM, Cercueil JP, Loffroy R, Denimal D, Bouillet B, Fourmont C, Chevallier O, Duvillard L, Verges B. Effect of Liraglutide Therapy on Liver Fat Content in Patients With Inadequately Controlled Type 2 Diabetes: The Lira-NAFLD Study. J Clin Endocrinol Metab. 2017 Feb 1;102(2):407-415. doi: 10.1210/jc.2016-2775.

  PMID: 27732328 RESULT

• Dungan KM, Povedano ST, Forst T, Gonzalez JG, Atisso C, Sealls W, Fahrbach JL. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet. 2014 Oct 11;384(9951):1349-57. doi: 10.1016/S0140-6736(14)60976-4. Epub 2014 Jul 10.

  PMID: 25018121 RESULT

• Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care. 2014 Aug;37(8):2149-58. doi: 10.2337/dc13-2761. Epub 2014 Apr 17.

  PMID: 24742660 RESULT

• Giorgino F, Benroubi M, Sun JH, Zimmermann AG, Pechtner V. Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2). Diabetes Care. 2015 Dec;38(12):2241-9. doi: 10.2337/dc14-1625. Epub 2015 Jun 18.

  PMID: 26089386 RESULT

• Patel NS, Peterson MR, Brenner DA, Heba E, Sirlin C, Loomba R. Association between novel MRI-estimated pancreatic fat and liver histology-determined steatosis and fibrosis in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013 Mar;37(6):630-9. doi: 10.1111/apt.12237. Epub 2013 Feb 5.

  PMID: 23383649 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

• Loomba R, Sirlin CB, Ang B, Bettencourt R, Jain R, Salotti J, Soaft L, Hooker J, Kono Y, Bhatt A, Hernandez L, Nguyen P, Noureddin M, Haufe W, Hooker C, Yin M, Ehman R, Lin GY, Valasek MA, Brenner DA, Richards L; San Diego Integrated NAFLD Research Consortium (SINC). Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology. 2015 Apr;61(4):1239-50. doi: 10.1002/hep.27647. Epub 2015 Feb 27.

  PMID: 25482832 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 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Interventions

dulaglutide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant

Model Details: will randomize the patients into either dulaglutide group or control group in a 1:1 ratio using computer-generated numbers

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: July 18, 2018
• Study Start: January 1, 2019
• Primary Completion: January 14, 2020
• Study Completion: February 18, 2020
• Last Updated: February 20, 2020

Record last verified: 2020-02

Locations

IN (1)