The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes

NCT02964715 | Unknown Phase 4 DMC

• 1 other identifier: ERF-4
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Non-Alcoholic Fatty Liver Disease( NAFLD) is common in patients with type 2 diabetes. Empagliflozin, an FDA-approved oral medication used to treat type 2 diabetes, has been shown to reduce production and deposition of fat in the liver in animal experiments. There is little published evidence that this is so in Asian patients with type 2 diabetes. The investigators designed this pilot study to determine if use of empagliflozin for 6 months in patients with type 2 diabetes can improve scan, blood marker and biopsy features of NAFLD.

Conditions

Type2 Diabetes; NAFLD

Outcome Measures

Primary Outcomes (2)

• Change in histological Grade as evaluated with Non-alcoholic Steatohepatitis Clinical Research Network Scoring System

  liver biopsy

  baseline, 6 months

• Change in serum FGF 21

  blood test

  baseline and 6 months

Secondary Outcomes (15)

• Change in fibroscan and elastography measure of liver stiffness

  baseline and 6 months

• Change in Liver enzymes

  baseline and 6 months

• Change in steatosis

  baseline and 6 months

• Change in lobular inflammation

  baseline and 6 months

• Change in ballooning

  baseline and 6 months

Study Arms (1)

Interventional arm

EXPERIMENTAL

Patients with NAFLD and Type 2 Diabetes prescribed 25mg empagliflozin(JARDIANCE) daily for 6 months

Drug: Empagliflozin

Interventions

Empagliflozin DRUG

25 mg daily for 6 months

Also known as: Jardiance

Interventional arm

Eligibility Criteria

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

You may qualify if:

• biopsy proven NASH
• Type 2 DM
• HbA1c :\>6.5%
• BMI \< 45kg/m2
• Any anti-diabetic agent except SGLT2 inhibitors, TZDs(thiazolidinediones), DPP4(Dipeptidyl peptidase4) inhibitors and GLP1 RAs(Glucagon-like Peptide 1-Receptor Agonists)

You may not qualify if:

• eGFR \<45 ml/min
• structural and functional urogenital abnormalities, that predispose for urogenital infections
• Investigational product use in the last 6 months
• SGLT2 inhibitor, TZD, DPP4 inhibitor and GLP1 RA use within the past 6 months
• DKA(Diabetic Ketoacidosis) or HHS(Hyperosmoloar Hyperglycaemic Syndrome) within the last 6 months
• Pregnancy
• Presence of major contraindications to magnetic resonance imaging (cardiac pacemakers, claustrophobia, foreign bodies and implanted medical devices with ferromagnetic properties).
• Liver cirrhosis
• Type 1 diabetes
• Severe uncorrected insulin insufficiency
• Significant alcohol intake
• HIV infection
• Use of Traditional Chinese Medication or alternative therapies
• Coexisting causes of chronic liver disease - chronic viral hepatitis(B \& C), autoimmune liver disease, hemochromatosis, Wilson's etc.
• Use of medications associated with steatosis eg. Methotrexate, anticonvulsants, antiretroviral therapy etc.

Sponsors & Collaborators

• University of Malaya: lead

Study Sites (1)

University of Malaya

Kuala Lumpur, Kuala Lumpur, Malaysia

RECRUITING

Related Publications (11)

• Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016 Mar 17;374(11):1094. doi: 10.1056/NEJMc1600827. No abstract available.

  PMID: 26981940 BACKGROUND

• Ferrannini E, Mark M, Mayoux E. CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis. Diabetes Care. 2016 Jul;39(7):1108-14. doi: 10.2337/dc16-0330.

  PMID: 27289126 BACKGROUND

• Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol. 2013 Sep 5;715(1-3):246-55. doi: 10.1016/j.ejphar.2013.05.014. Epub 2013 May 23.

  PMID: 23707905 BACKGROUND

• Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism. 2016 Aug;65(8):1096-108. doi: 10.1016/j.metabol.2016.01.001. Epub 2016 Jan 11.

  PMID: 26856933 BACKGROUND

• Ballestri S, Nascimbeni F, Romagnoli D, Lonardo A. The independent predictors of non-alcoholic steatohepatitis and its individual histological features.: Insulin resistance, serum uric acid, metabolic syndrome, alanine aminotransferase and serum total cholesterol are a clue to pathogenesis and candidate targets for treatment. Hepatol Res. 2016 Oct;46(11):1074-1087. doi: 10.1111/hepr.12656. Epub 2016 Mar 30.

  PMID: 26785389 BACKGROUND

• Jojima T, Tomotsune T, Iijima T, Akimoto K, Suzuki K, Aso Y. Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes. Diabetol Metab Syndr. 2016 Jul 26;8:45. doi: 10.1186/s13098-016-0169-x. eCollection 2016.

  PMID: 27462372 BACKGROUND

• Alisi A, Ceccarelli S, Panera N, Prono F, Petrini S, De Stefanis C, Pezzullo M, Tozzi A, Villani A, Bedogni G, Nobili V. Association between Serum Atypical Fibroblast Growth Factors 21 and 19 and Pediatric Nonalcoholic Fatty Liver Disease. PLoS One. 2013 Jun 26;8(6):e67160. doi: 10.1371/journal.pone.0067160. Print 2013.

  PMID: 23840612 BACKGROUND

• Dushay JR, Toschi E, Mitten EK, Fisher FM, Herman MA, Maratos-Flier E. Fructose ingestion acutely stimulates circulating FGF21 levels in humans. Mol Metab. 2014 Oct 8;4(1):51-7. doi: 10.1016/j.molmet.2014.09.008. eCollection 2015 Jan.

  PMID: 25685689 BACKGROUND

• Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21. doi: 10.1002/hep.20701.

  PMID: 15915461 BACKGROUND

• Vanni E, Bugianesi E, Kotronen A, De Minicis S, Yki-Jarvinen H, Svegliati-Baroni G. From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis. 2010 May;42(5):320-30. doi: 10.1016/j.dld.2010.01.016. Epub 2010 Mar 6.

  PMID: 20207596 BACKGROUND

• Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK. Empagliflozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus. Dig Dis Sci. 2020 Feb;65(2):623-631. doi: 10.1007/s10620-019-5477-1. Epub 2019 Jan 25.

  PMID: 30684076 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Shireene R Vethakkan, MD

  University of Malaya

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shireene R Vethakkan, MD

CONTACT

0162093355; shireene.vethakkan@gmail.com

Wah K Chan, MRCP

CONTACT

0163655232; wahkheong2003@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Dr.

Study Record Dates

• First Submitted: October 30, 2016
• First Posted: November 16, 2016
• Study Start: November 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: May 31, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)