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Type 2 DiabetesPhase 4COMBAT_T2_NASHNCT04639414

Combined Active Treatment in Type 2 Diabetes With NASH

A Phase 4 study testing Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector in people with Type 2 Diabetes and Non-alcoholic Steatohepatitis (NASH), run by German Diabetes Center at 26 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 25 to 75 years
What is being tested?
Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
192 participants
Where
26 sitesin 2 countries
Study dates
26 Mar 2021to 17 Nov 2025
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of T2D and NASH with fibrosis stage F1-F3
  • Age between 25 and 75 years
  • HbA1c ≤ 9.5%
  • obtained written informed consent

Who cannot join

  • 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

Trial locations and contacts

26 sites in 2 countries.

26 sites in 2 countries

Germany21 sites

  • Herz- und Diabeteszentrum NRW

    Bad Oeynhausen, 32545

  • Franziskus-Krankenhaus Berlin

    Berlin, 10787

  • Leber- und Studienzentrum Checkpoint

    Berlin, 10961

  • University Clinics Berlin Charité

    Berlin, 12200

  • University Clinics Berlin Charité

    Berlin, 13353

  • University Clinics Bochum

    Bochum, 44892

  • Städtisches Klinikum Brandenburg GmbH

    Brandenburg, 14770

  • Städtisches Klinikum Braunschweig gGmbH

    Braunschweig, 38126

  • University Clinics Carl Gustav Carus Dresden

    Dresden, 01307

  • German Diabetes Center

    Düsseldorf, North Rhine-Westphalia, 40225

  • Universitätsklinikum Düsseldorf

    Düsseldorf, 40225

  • University Clinics Essen

    Essen, 45147

  • University Clinics Frankfurt

    Frankfurt, 60590

  • University Clinics Freiburg

    Freiburg im Breisgau, 79106

  • University Clinics Heidelberg

    Heidelberg, 69120

  • Eugastro GmbH

    Leipzig, 04103

  • University Clinics Johannes-Gutenberg Mainz

    Mainz, 55131

  • TUM

    München, 81675

  • University Clinics Tübingen

    Tübingen, 72076

  • Universitätsklinikum Ulm

    Ulm, 89081

  • University Clinics Würzburg

    Würzburg, 97080

Other trials in Germany

Austria5 sites

  • Medizinische Universität Graz

    Graz, 8010

  • Medizinische Universität Innsbruck

    Innsbruck

  • Wiener Gesundheitsverbund, Klinik Landstraße

    Vienna, 1030

  • Medizinische Universität Wien

    Vienna

  • Wiener Gesundheitsverbund, Klinik Hietzing

    Vienna

Other trials in Austria

About this study

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.

Read the 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.

Being tested
Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector, Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide, Placebo matching empagliflozin and placebo pen injector matching semaglutide
Keywords
Type 2 Diabetes, Non-alcoholic Steatohepatitis (NASH), Non-alcoholic Fatty Liver Disease (NAFLD), Fatty liver, Diabetes mellitus, Empagliflozin, Semaglutide
Medical subject headings
Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease, Fatty Liver, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injectorDrug

    Also called Jardiance(R), Ozempic(R)

    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.

  • Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutideDrug

    Also called Jardiance(R)

    Measurement of the effect of empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.

  • Placebo matching empagliflozin and placebo pen injector matching semaglutideDrug

    Also called Control / Placebo

    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.

Study groups in NCT04639414
Study groupRoleWhat they receive
Combined treatment with Empagliflozin and SemaglutideExperimentalCombined treatment with Empagliflozin, film-coated tablet, 10mg once daily and Semaglutide, colourless solution in pre-filled pen, 1mg once weekly
Receives: Drug: Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector
Empagliflozin monotherapyExperimentalEmpagliflozin, film-coated tablet, 10mg once daily and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)
Receives: Drug: Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide
PlaceboPlacebo comparatorPlacebo matching Empagliflozin (film-coated tablet, once daily) and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)
Receives: Drug: Placebo matching empagliflozin and placebo pen injector matching semaglutide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Histological resolution of NASH without worsening of fibrosis

    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.

    Measured: from baseline to 48 weeks

Secondary outcomes (4)

  1. Overall NAFLD activity score (NAS)

    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

    Measured: from baseline to 48 weeks

  2. Stage of fibrosis according to the Kleiner Fibrosis Classification

    Assessed by liver histology according to the Kleiner Fibrosis Classification (stages 0-4)

    Measured: from baseline to 48 weeks

  3. Activity component of NASH according to the steatosis-activity-fibrosis (SAF) score

    Sum of lobular inflammation (scored 0-3 points)and hepatocellular ballooning (scored 0-2 points) assessed by liver histology

    Measured: from baseline to 48 weeks

  4. Hepatic steatosis grade

    steatosis grade (0-3) assessed by liver histology

    Measured: from baseline to 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2020
  2. Study start26 Mar 2021
  3. Primary completion31 Jan 2025
  4. Study completion17 Nov 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
192 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04639414
Sponsor's protocol ID
Combat_T2_NASH_002
Other IDs
2019-001987-31, 2019
Acronym
COMBAT_T2_NASH
Status last verified
Nov 2025
First submitted
5 Apr 2019
Last updated
8 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector in people with Type 2 Diabetes and Non-alcoholic Steatohepatitis (NASH), run by German Diabetes Center at 26 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Histological resolution of NASH without worsening of fibrosis (time frame: from baseline to 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04639414.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.

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