DRUG
Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector
Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d compared to matching placebo after 48-week treatment.
Combined Active Treatment in Type 2 Diabetes With NASH
Status
Completed
Phase
Phase 4
Enrollment
192
Locations
26
Results
Not posted
Publications
0
Study summary
What the protocol is testing.
The aim of this multicentre, prospective, placebo-controlled, double-blind, randomized, 3-arm parallel group, interventional study is to assess for the first time the effects of either a combined therapy with the antihyperglycemic drugs semaglutide and empagliflozin or empagliflozin monotherapy compared to placebo as potential treatments for non-alcoholic steatohepatitis (NASH) in patients with type 2 diabetes.
Full detailed description
Obesity and type 2 diabetes (T2D) are tightly associated with non-alcoholic fatty liver disease (NAFLD), which in turn predicts the development of T2D and cardiovascular disease. Up to 80% of NAFLD patients with T2D have NASH and the presence of T2D is an independent risk factor for more-advanced fibrosis, higher rate of fibrosis progression, and increased mortality. Liver-related mortality is increased 10-fold in NASH patients compared with the general population. In addition, people with NASH are at an excessive risk of cardiovascular morbidity and mortality. Currently, there are no established pharmacotherapies for NASH patients with T2D. The aim of this trial is to evaluate efficacy of a combined treatment with semaglutide 1 mg/week (GLP1RA) and empagliflozin 10 mg/d (SGLT2I) or ii) empagliflozin 10 mg/d monotherapy by means of histological resolution of NASH in T2D patients without progression of fibrosis after 48 weeks treatment. To confirm a histological diagnosis of NASH and proof efficacy of treatment, a liver biopsy will be performed prior to screening as well as at the end of treatment phase.
Interventions
Treatment arms and agents.
DRUG
Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide
Measurement of the effect of empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.
DRUG
Placebo matching empagliflozin and placebo pen injector matching semaglutide
Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d OR empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.
Timeline
From registration to results.
First posted
Nov 20, 2020
Study start
Mar 26, 2021
Primary completion
Jan 31, 2025
Study completion
Nov 17, 2025
Results posted
Not reported
Registry updated
Jul 8, 2026
Outcomes
What the study measures.
Primary outcomes
Histological resolution of NASH without worsening of fibrosis
Time frame · from baseline to 48 weeks
NAFLD status will be assessed by histologic evaluation of liver biopsy samples based on NAFLD activity score. NASH resolution is defined by disappearance of ballooning (score 0), together with either disappearance of lobular inflammation or the persistence of mild lobular inflammation only (score 0 or 1) and resulting in an overall pathologic diagnosis of either steatosis alone or steatosis with mild inflammation; with no worsening of fibrosis. Worsening of fibrosis is defined by an increase of at least one stage of the Kleiner fibrosis classification.
Secondary outcomes
Overall NAFLD activity score (NAS)
Time frame · from baseline to 48 weeks
Sum of a) steatosis (0-3 points), b) lobular inflammation (scored 0-3 points), c) hepatocellular ballooning (scored 0-2 points) assessed by liver histology
Stage of fibrosis according to the Kleiner Fibrosis Classification
Time frame · from baseline to 48 weeks
Assessed by liver histology according to the Kleiner Fibrosis Classification (stages 0-4)
Activity component of NASH according to the steatosis-activity-fibrosis (SAF) score
Time frame · from baseline to 48 weeks
Sum of lobular inflammation (scored 0-3 points)and hepatocellular ballooning (scored 0-2 points) assessed by liver histology
Hepatic steatosis grade
Time frame · from baseline to 48 weeks
steatosis grade (0-3) assessed by liver histology
Eligibility
Who can take part.
- Minimum age
- 25 Years
- Maximum age
- 75 Years
- Sex
- ALL
- Healthy volunteers
- No
Inclusion Criteria: * Diagnosis of T2D and NASH with fibrosis stage F1-F3 * Age between 25 and 75 years * HbA1c ≤ 9.5% * obtained written informed consent Exclusion Criteria: * Contraindications on liver biopsy * Evidence of cirrhosis on liver biopsy * Liver disease of other etiology including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis, or liver cirrhosis of any etiology * History of ketoacidosis * Alcohol consumption \>30 g/d for males and \>20 g/d for females * Past (≥5 years) or current history of alcohol or drug abuse and/or psychiatric disease including severe depression necessitating pharmacological treatment * Medications that may induce steatosis:tamoxifen, raloxifene, oral glucocorticoids or chloroquine * Planned pregnancy, pregnant or lactating women, positive pregnancy test, and woman of childbearing potential not using two adequate methods of contraception, including a barrier method and a highly efficacious non-barrier method
Study locations
26 registered sites.
Austria · Germany. Showing up to 24 locations stored in the fast local snapshot.
Medizinische Universität Graz
Graz, Austria
Medizinische Universität Innsbruck
Innsbruck, Austria
Wiener Gesundheitsverbund, Klinik Landstraße
Vienna, Austria
Medizinische Universität Wien
Vienna, Austria
Wiener Gesundheitsverbund, Klinik Hietzing
Vienna, Austria
German Diabetes Center
Düsseldorf, North Rhine-Westphalia, Germany
Herz- und Diabeteszentrum NRW
Bad Oeynhausen, Germany
Franziskus-Krankenhaus Berlin
Berlin, Germany
Leber- und Studienzentrum Checkpoint
Berlin, Germany
University Clinics Berlin Charité
Berlin, Germany
University Clinics Berlin Charité
Berlin, Germany
University Clinics Bochum
Bochum, Germany
Städtisches Klinikum Brandenburg GmbH
Brandenburg, Germany
Städtisches Klinikum Braunschweig gGmbH
Braunschweig, Germany
University Clinics Carl Gustav Carus Dresden
Dresden, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, Germany
University Clinics Essen
Essen, Germany
University Clinics Frankfurt
Frankfurt, Germany
University Clinics Freiburg
Freiburg im Breisgau, Germany
University Clinics Heidelberg
Heidelberg, Germany
Eugastro GmbH
Leipzig, Germany
University Clinics Johannes-Gutenberg Mainz
Mainz, Germany
TUM
München, Germany
University Clinics Tübingen
Tübingen, Germany
Publications
Results and literature.
No PMID-linked publications were present in this registry snapshot.
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